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Abukmail E, Pradeep NK, Ahmed S, Albarqouni L. Moderate- to Long-Term Effect of Dietary Interventions for Depression and Anxiety : A Systematic Review and Meta-analysis. Ann Intern Med 2025. [PMID: 40388814 DOI: 10.7326/annals-24-03016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/21/2025] Open
Abstract
BACKGROUND Dietary interventions are a potential alternative treatment of depression and anxiety. PURPOSE To evaluate the effects of dietary interventions on depression and anxiety. DATA SOURCES PubMed, Cochrane CENTRAL, EMBASE, CINAHL, and PsycINFO searched from inception until 12 December 2024. Trial registries and forward and backward citation analysis done on 3 January 2025. STUDY SELECTION Randomized controlled trials (RCTs) evaluated the effect of dietary advice with or without food provision compared with no specific dietary advice or active interventions for 3 months or longer on depression and/or anxiety. DATA EXTRACTION Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes included depression and anxiety symptoms at 3 months or longer. Random-effects meta-analyses were done, and the certainty of evidence was assessed. DATA SYNTHESIS Twenty-five RCTs were included. Compared with no specific dietary advice, depressive symptoms might be improved in adults with elevated cardiometabolic risk by dietary advice on calorie restriction (standardized mean difference [SMD], -0.23 [95% CI, -0.38 to -0.09]; low certainty). Low-fat diets may also have very small effects on depressive symptoms in adults with elevated cardiometabolic risk (SMD, -0.03 [CI, -0.04 to -0.01]; low certainty). Evidence on other diets, comparing diets with active comparisons, and on anxiety was limited by study limitations and clinical or methodological heterogeneity. LIMITATION Limited studies did not allow for adequate exploration of heterogeneity. CONCLUSION Calorie restrictions and low-fat diets might reduce depressive symptoms among adults with elevated cardiometabolic risk, but the differences were small and confidence in the findings was low. Evidence on other diets, comparisons to active interventions, and other outcomes is limited. PRIMARY FUNDING SOURCE None. (PROSPERO: CRD42023485953).
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Affiliation(s)
- Eman Abukmail
- Institute for Evidence Based Healthcare and Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia (E.A., S.A., L.A.)
| | - Neeraj Koloth Pradeep
- Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia (N.K.P.)
| | - Samantha Ahmed
- Institute for Evidence Based Healthcare and Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia (E.A., S.A., L.A.)
| | - Loai Albarqouni
- Institute for Evidence Based Healthcare and Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia (E.A., S.A., L.A.)
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Fluyau D, Kailasam VK, Kim P, Revadigar N. Selective serotonin reuptake inhibitors and quality of life: a meta-analysis of randomized placebo-controlled trials. Int Clin Psychopharmacol 2025:00004850-990000000-00163. [PMID: 40014013 DOI: 10.1097/yic.0000000000000585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
The benefit of selective serotonin reuptake inhibitors (SSRIs) in improving quality of life (QoL) has been investigated in randomized-controlled trials (RCTs) with equivocal results. This study explored whether SSRIs could improve QoL in individuals with medical, psychiatric, and neuropsychiatric conditions. RCTs were searched in PubMed, Embase, Scopus, Ovid, and Google Scholar. Data were synthesized via a meta-analysis. Subgroup and meta-regression analyses were performed. The sample size was 9,070. Compared with placebo, SSRIs showed statistically significant improvements in QoL in cancer (d = 0.30), major depressive disorder (d = 0.27), premenstrual dysphoric disorder (d = 0.38), type 2 diabetes mellitus (d = 0.48), persistent depressive disorder (d = 0.32), and menopausal symptoms (d = 0.40). Paroxetine exhibited the highest effect size. No significant improvements were noted in chronic obstructive pulmonary disease (d = 0.65, P = 0.09), congestive heart failure (d = 0.46, P = 0.27), and irritable bowel syndrome (d = 0.26, P = 0.127). The reduction in depressive symptoms improved QoL. Small-study effects, high attrition rates, and demographic imbalances are limiting factors to recommend SSRIs to improve QoL. Future research should focus on QoL domains and pharmacological properties of each SSRI.
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Affiliation(s)
- Dimy Fluyau
- Department of Psychiatry and Behavioral Sciences, Emory School of Medicine, Emory University, Atlanta, Georgia
| | - Vasanth Kattalai Kailasam
- Department of Psychiatry, College of Medicine at Chicago, University of Illinois, Rockford, Illinois
| | - Paul Kim
- Department of Psychiatry and Behavioral Sciences, Emory School of Medicine, Emory University, Atlanta, Georgia
| | - Neelambika Revadigar
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA
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3
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Liu C, Ye X, Chen M. Sertraline medications plus dialectical behavior therapy for depressed adolescents with nonsuicidal self-injury behaviors. Suicide Life Threat Behav 2025; 55:e13132. [PMID: 39400437 PMCID: PMC11716346 DOI: 10.1111/sltb.13132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/14/2024] [Accepted: 10/02/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVE The study aims to investigate the efficacy of sertraline medication plus dialectical behavior therapy (DBT) in reducing nonsuicidal self-injury (NSSI) behavior and depression among adolescents. METHODS Participants were 100 adolescents with depression and NSSI behaviors, 50 of whom received sertraline medication plus DBT and 50 of whom received sertraline medication plus cognitive behavioral therapy (CBT) for 12 weeks. RESULTS During 6 months post intervention, 26 (57.8%) participants did not report having engaged in any form of NSSI in the sertraline + DBT group and 15 (32.6%) in the sertraline + CBT group, showing significant difference. The sertraline + DBT group and the sertraline + CBT group exhibited significant difference regarding the proportions of cutting skin and biting self. The scores of anxiety, depression, aggression against self in four modified overt aggression scale categories, and Personal and Social Performance were notably lower in the sertraline + DBT group than those in the sertraline + CBT group at 6 months post intervention. CONCLUSION Sertraline medication plus DBT could decrease NSSI episodes and improve symptoms of anxiety and depression for adolescents, and these changes were comparable to those of CBT. More importantly, DBT was demonstrated better clinical improvements at 6-month follow-up.
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Affiliation(s)
- Chaoqun Liu
- PsychiatryWenzhou Seventh People's HospitalWenzhouZhejiangChina
| | - Xinwu Ye
- PsychiatryWenzhou Seventh People's HospitalWenzhouZhejiangChina
| | - Minshan Chen
- PsychiatryWenzhou Seventh People's HospitalWenzhouZhejiangChina
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Li Y, Chen Y, Jiang Y, Wang W, Guo L, Fan B, Liu Y, Zhang H, Lin X, Teopiz KM, McIntyre RS, Lu C, Han X. Associations of childhood trauma with remission and treatment response after 12 weeks of selective serotonin reuptake inhibitor treatment in patients with major depressive disorder. Gen Hosp Psychiatry 2025; 92:12-19. [PMID: 39662212 DOI: 10.1016/j.genhosppsych.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/20/2024] [Accepted: 12/01/2024] [Indexed: 12/13/2024]
Abstract
OBJECTIVE To explore the associations of childhood trauma and its subtypes with remission and treatment response after 12 weeks of selective serotonin reuptake inhibitor (SSRI) treatment among patients with major depressive disorder (MDD). METHODS Data were from patients with MDD in the Depression Cohort in China. At baseline, the Childhood Trauma Questionnaire-Short Form was used to assess childhood trauma, including physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect. After 12 weeks of SSRI treatment, depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). Remission was defined as a PHQ-9 score < 5, and response was defined as a ≥ 50 % decline in the PHQ-9 score from baseline. RESULTS The sample included 572 patients with MDD (mean [SD] age, 27.4 [7.2] years; 30.6 % male). After receiving 12 weeks of SSRI treatment, 32.2 % of patients achieved remission and 49.1 % of patients responded to treatment. After fully adjusting for confounders, patients with childhood trauma (OR, 0.55; 95 % CI, 0.36 to 0.84), physical abuse (OR, 0.43; 95 % CI, 0.23 to 0.79), emotional abuse (OR, 0.40; 95 % CI, 0.24 to 0.67), or sexual abuse (OR, 0.49; 95 % CI, 0.24 to 0.99) had a lower likelihood of remission, but those with physical neglect or emotional neglect did not. The response showed similar results. CONCLUSIONS Among patients with MDD, childhood abuse (i.e., physical abuse, emotional abuse, and sexual abuse), but not childhood neglect (i.e., physical neglect and emotional neglect), was associated with a lower likelihood of remission and response after 12 weeks of SSRI treatment.
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Affiliation(s)
- Yanzhi Li
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Yan Chen
- Department of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Yingchen Jiang
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Wanxin Wang
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Lan Guo
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Beifang Fan
- Department of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Yifeng Liu
- Department of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Huimin Zhang
- Department of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Xinyi Lin
- Department of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China
| | - Kayla M Teopiz
- Brain and Cognition Discovery Foundation, Toronto, ON, Canada
| | - Roger S McIntyre
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Ciyong Lu
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Sun Yat-sen University, Guangzhou 510080, China.
| | - Xue Han
- Department of Psychiatry, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China.
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You S, Hao X, Cao F, Lou J, Cao J, Liu Y, Guo Y, Li H, Li A, Xu J, Wu Q, Gu X, Feng Y, Peng Y, Ma L, Zhou Z, Wu R, Mi W, Tong L. Effects of volatile anaesthetics on incidence of postoperative depression and anxiety symptoms in elderly patients: A retrospective analysis of a prospective cohort study. J Psychiatr Res 2025; 181:179-187. [PMID: 39615081 DOI: 10.1016/j.jpsychires.2024.11.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 08/03/2024] [Accepted: 11/21/2024] [Indexed: 01/22/2025]
Abstract
Studies have suggested volatile anaesthetics may alleviate depression and anxiety symptoms in patients. However, there is a paucity of research in this area. We wanted to determine the association between volatile anaesthetics and depression/anxiety symptoms in elderly patients within 7 days after surgery. This study retrospectively analysed data from a prospective database of patients aged 65 and above who underwent non-cardiac, non-neurosurgical elective surgery in 19 tertiary hospitals across 10 provinces in China. The study period spanned from April 1, 2020 to April 30, 2022. Patients receiving volatile anaesthetics received at least one volatile anaesthetic (sevoflurane, isoflurane, desflurane), and those who received non-volatile anaesthetics did not receive any volatile anaesthetic. Binary logistic regression analyses were conducted, and propensity score-matching (PSM) and subgroup analyses were also applied. A total of 7165 patients were included in the analysis. Among them, 4957 (69.18%) cases received volatile anaesthetics. The administration of volatile anaesthetics was associated with a lower rate of postoperative depression [22.76% vs. 27.26%, odds ratio (OR): 0.75, P < 0.001], and reduced the incidence of postoperative anxiety (19.59% vs. 24.68%, OR: 0.78, P < 0.001). The risk of postoperative depression (24.78% vs.27.93%, OR: 0.85, P = 0.035), and anxiety (21.45% vs. 25.92%, OR: 0.81, P = 0.006) were both significantly decreased in the volatile anaesthetics group in the PSM cohort. The results suggest that using volatile anaesthetics maybe associated with a reduction in the incidence of depression and anxiety in elderly patients during the early postoperative period.
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Affiliation(s)
- Shaohua You
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China; Department of Pain Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Xinyu Hao
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Fuyang Cao
- Department of Anesthesiology, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China
| | - Jingsheng Lou
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Jiangbei Cao
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Yanhong Liu
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Yongxin Guo
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Hao Li
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Ao Li
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Junmei Xu
- Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Qingping Wu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaoping Gu
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Medical College of Nanjing University, Nanjing, China
| | - Yi Feng
- Department of Anesthesiology, Peking University People's Hospital, Beijing, China
| | - Yuming Peng
- Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Libin Ma
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Zhikang Zhou
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Ruiyu Wu
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Weidong Mi
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China; National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, China.
| | - Li Tong
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
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Duo LL, Rao GF. Wuling capsule combined with sertraline in the therapy of anxiety and depression with insomnia in adolescents. World J Psychiatry 2024; 14:1860-1867. [PMID: 39704352 PMCID: PMC11622017 DOI: 10.5498/wjp.v14.i12.1860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/15/2024] [Accepted: 11/11/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND The treatment of adolescent patients with anxiety, depression and insomnia is challenging, and there is no ideal treatment method. AIM To evaluate the clinical efficacy of Wuling capsule combined with sertraline in the treatment of adolescent anxiety, depression and insomnia. METHODS Eighty adolescent patients with anxiety, depression with insomnia who were admitted to our hospital from April 1, 2022 to March 30, 2024. And the subjects were randomly classified into the control group (n = 40) and the observational group (n = 40). The control group was treated with a combination of sertraline and placebo. The observation group was treated with Wuling capsule in addition to sertraline. The two groups were cured continuously for 8 weeks. Insomnia severity index (ISI), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to evaluate the clinical symptoms before treatment and at 2, 4, 6 and 8 weeks after treatment. The Treatment Emergent Symptom Scale (TESS) was used to evaluate adverse reactions during treatment. RESULTS There was no obvious difference in HAMD, HAMA and ISI scores between the two groups before treatment (P > 0.05). After treatment, the HAMD, HAMA and ISI scores of patients in both groups decreased compared with before treatment, and HAMD, HAMA and ISI scores of patients in the observation group were remarkedly lower than those in the control group at each time point after treatment (P < 0.05). Compared with the control group, the TESS score of the study group were sharply lower (t = 18.239, P < 0.001). CONCLUSION Wuling capsule can further alleviate the insomnia symptoms of adolescents with anxiety and depression, and the efficacy and safety are high. It is recommended to promote the application.
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Affiliation(s)
- Li-Li Duo
- Department of Psychiatry, Taizhou Integrated Traditional Chinese and Western Medicine Hospital, Taizhou 317500, Zhejiang Province, China
| | - Gao-Feng Rao
- Department of Rehabilitation, Taizhou Integrated Traditional Chinese and West Medicine Hospital, Taizhou 317500, Zhejiang Province, China
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Ye J, Bi X, Deng S, Wang X, Liu Z, Suo Q, Wu J, Chen H, Wang Y, Qian K, Shi R, Zhao J, Yang GY, Ye J, Tang Y. Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke. Theranostics 2024; 14:6071-6087. [PMID: 39346547 PMCID: PMC11426240 DOI: 10.7150/thno.100090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/06/2024] [Indexed: 10/01/2024] Open
Abstract
Rationale: Stroke induces metabolic changes in the body, and metabolites have become potential biomarkers for stroke. However, the specific metabolites involved in stroke and the mechanisms underlying brain injury during stroke remain unclear. Methods: Surface-enhanced Raman spectroscopy (SERS) and liquid chromatography-mass spectrometry (LC‒MS) analysis of clinical serum samples from 69 controls and 51 ischemic stroke patients who underwent reperfusion within 24 hours were performed to identify differentially abundant metabolites. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) and then intravenously injected with hypoxanthine. The infarct area was evaluated via tetrazolium chloride (TTC) staining, and behavior tests were conducted. Blood-brain barrier (BBB) leakage was assessed by Evans blue and IgG staining. Human blood vessel organoids were used to investigate the mechanism of hypoxanthine-induced pyroptosis of endothelial cells. Results: SERS and LC‒MS revealed the metabolic profiles of serum from stroke patients and controls with high sensitivity, speed and accuracy. Hypoxanthine levels were significantly elevated in the acute stage of ischemic stroke in both patients and mice (p < 0.001 after Bonferroni correction). In addition, increasing hypoxanthine increased the infarct area and aggravated BBB leakage and neurobehavioral deficits in mice after ischemic stroke. Further mechanistic studies using endothelial cells, human blood vessel organoids, and stroke mice demonstrated that hypoxanthine-mediated gasdermin E (GSDME)-dependent pyroptosis of endothelial cells occurs through intracellular Ca2+ overload. Conclusion: Our study identified hypoxanthine as an important metabolite that induces vascular injury and BBB disruption in stroke through triggering GSDME-dependent pyroptosis of endothelial cells.
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Affiliation(s)
- Jing Ye
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Xinyuan Bi
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Shiyu Deng
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Xianghui Wang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Ze Liu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Qian Suo
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Jiao Wu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
- Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Haoran Chen
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Yong Wang
- Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200030, China
| | - Kun Qian
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
- Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Rubing Shi
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Jing Zhao
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201102, China
| | - Guo-Yuan Yang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Jian Ye
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
- Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Yaohui Tang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
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Malamud J, Lewis G, Moutoussis M, Duffy L, Bone J, Srinivasan R, Lewis G, Huys QJM. The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial. Psychol Med 2024; 54:2719-2731. [PMID: 38629200 DOI: 10.1017/s0033291724000837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).
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Affiliation(s)
- Jolanda Malamud
- Applied Computational Psychiatry Lab, Mental Health Neuroscience Department, Division of Psychiatry and Max Planck Centre for Computational Psychiatry and Ageing Research, Queen Square Institute of Neurology, University College London, London, UK
| | - Gemma Lewis
- Division of Psychiatry, University College London, London, UK
| | - Michael Moutoussis
- Max Planck UCL Centre for Computational Psychiatry & Ageing Research, University College London, London, UK
- Wellcome Centre for Human Neuroimaging, Queen Square Institute of Neurology, University College London, London, UK
| | - Larisa Duffy
- Division of Psychiatry, University College London, London, UK
| | - Jessica Bone
- Division of Psychiatry, University College London, London, UK
- Research Department of Behavioural Science and Health, Institute of Epidemiology, University College London, London, UK
| | | | - Glyn Lewis
- Division of Psychiatry, University College London, London, UK
| | - Quentin J M Huys
- Applied Computational Psychiatry Lab, Mental Health Neuroscience Department, Division of Psychiatry and Max Planck Centre for Computational Psychiatry and Ageing Research, Queen Square Institute of Neurology, University College London, London, UK
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Haller J. Herbal Cannabis and Depression: A Review of Findings Published over the Last Three Years. Pharmaceuticals (Basel) 2024; 17:689. [PMID: 38931356 PMCID: PMC11206863 DOI: 10.3390/ph17060689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a review of research studies published over the last three years. We found 156 relevant research articles. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Although medical cannabis reduced depression in most studies, none of these were placebo-controlled. In clinical studies published in the same period, the placebo also ameliorated depression and, in addition, the average effect size of the placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.
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Affiliation(s)
- Jozsef Haller
- Drug Research Institute, 1137 Budapest, Hungary;
- Department of Criminal Psychology, Faculty of Law Enforcement, Ludovika University of Public Service, 1083 Budapest, Hungary
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Atiq MA, Baker MR, Voort JLV, Vargas MV, Choi DS. Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties. Psychopharmacology (Berl) 2024:10.1007/s00213-024-06599-5. [PMID: 38743110 DOI: 10.1007/s00213-024-06599-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 04/24/2024] [Indexed: 05/16/2024]
Abstract
Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the acute subjective effects (ASE) under the influence of psychedelics and their enduring therapeutic properties. However, with potential barriers to widespread clinical implementation, including the healthcare resource-intensive nature of psychedelic sessions and the exclusion of certain at-risk patient groups, there is an active search to determine whether ASE elimination can be accompanied by the retention of persisting therapeutic benefits of these class of compounds. Recognizing the aberrant underlying neural circuitry that characterizes a range of neuropsychiatric disorders, and that classic psychedelics promote neuroplastic changes that may correct abnormal circuitry, investigators are rushing to design and discover compounds with psychoplastogenic, but not hallucinogenic (i.e., ASE), therapeutic potential. These efforts have paved the discovery of 'non-psychedelic/subjective psychedelics', or compounds that lack hallucinogenic activity but with therapeutic efficacy in preclinical models. This review aims to distill the current evidence - both clinical and preclinical - surrounding the question: can the ASE of classic psychedelics be dissociated from their sustained therapeutic properties? Several plausible clinical scenarios are then proposed to offer clarity on and potentially answer this question.
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Affiliation(s)
- Mazen A Atiq
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
| | - Matthew R Baker
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - Jennifer L Vande Voort
- Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - Maxemiliano V Vargas
- Institute for Psychedelics and Neurotherapeutics, University of California, Davis, Davis, CA, USA
| | - Doo-Sup Choi
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
- Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
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11
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Archer C, Kessler D, Lewis G, Araya R, Duffy L, Gilbody S, Lewis G, Kendrick T, Peters TJ, Wiles N. What predicts response to sertraline for people with depression in primary care? a secondary data analysis of moderators in the PANDA trial. PLoS One 2024; 19:e0300366. [PMID: 38722970 PMCID: PMC11081306 DOI: 10.1371/journal.pone.0300366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 02/23/2024] [Indexed: 05/13/2024] Open
Abstract
PURPOSE Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.
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Affiliation(s)
- Charlotte Archer
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - David Kessler
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Gemma Lewis
- Division of Psychiatry, University College London, London, United Kingdom
| | - Ricardo Araya
- Health Services and Population Research Department, King’s College London, London, United Kingdom
| | - Larisa Duffy
- Division of Psychiatry, University College London, London, United Kingdom
| | - Simon Gilbody
- Department of Health Sciences, University of York, York, United Kingdom
- Hull York Medical School, University of York, York, United Kingdom
| | - Glyn Lewis
- Division of Psychiatry, University College London, London, United Kingdom
| | - Tony Kendrick
- Faculty of Medicine, Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, United Kingdom
| | - Tim J. Peters
- Bristol Dental School, University of Bristol, Bristol, United Kingdom
| | - Nicola Wiles
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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12
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Mohan P, Chatterjee K, Sinha S, Saini R, Sharma A, Waikole S. Smoking blunts sertraline response in depression: A prospective observational cohort study. Med J Armed Forces India 2024; 80:145-152. [PMID: 38525466 PMCID: PMC10954491 DOI: 10.1016/j.mjafi.2021.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 10/15/2021] [Indexed: 10/19/2022] Open
Abstract
Background Smoking is common in patients of depression and is known to affect response to antidepressants. This study was undertaken to evaluate the effect of smoking on the antidepressant effect of sertraline. Method Patients with depression were divided into smoker and nonsmoker cohorts and followed up for 8 weeks. Serum sertraline levels were estimated using the high-performance liquid chromatography system. Response to treatment was evaluated with the Hamilton Depression Rating Scale (HAM-D). Results Serum sertraline levels did not differ between smokers and nonsmokers at 4 and 8 weeks. Nonsmokers responded better to sertraline than smokers after 8 weeks. Adverse drug reaction profile did not vary between the two groups and was not impacted by serum sertraline levels. Nonsmokers showed a greater fall in the HAM-D score than smokers. Conclusion This study found depression among smokers to be less responsive to sertraline. This was not explained by serum sertraline levels. Treatment of depression in smokers with sertraline might require higher doses and duration, with more frequent reviews.
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Affiliation(s)
- Prafull Mohan
- Classified Specialist (Pharmacology) & Commanding Officer, 421 Field Hospital, C/o 99 APO, India
| | - Kaushik Chatterjee
- Professor & Head, Department of Psychiatry, Armed Forces Medical College, Pune, India
| | - Sharmila Sinha
- Professor & Head, Department of Pharmacology, Armed Forces Medical College, Pune, India
| | - R.K. Saini
- Senior Adviser (Psychiatry), Command Hospital (Eastern Command), Kolkata, India
| | - A.K. Sharma
- Ex-Professor & Head, Department of Pharmacology, Armed Forces Medical College, Pune, India
| | - Suraj Waikole
- Resident, Department of Pharmacology, Armed Forces Medical College, Pune, India
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13
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Rai D, Webb D, Lewis A, Cotton L, Norris JE, Alexander R, Baldwin DS, Brugha T, Cochrane M, Del Piccolo MC, Glasson EJ, Hatch KK, Kessler D, Langdon PE, Leonard H, MacNeill SJ, Mills N, Morales MV, Morgan Z, Mukherjee R, Realpe AX, Russell A, Starkstein S, Taylor J, Turner N, Thorn J, Welch J, Wiles N. Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial. Trials 2024; 25:37. [PMID: 38212784 PMCID: PMC10782796 DOI: 10.1186/s13063-023-07847-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 11/30/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.
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Affiliation(s)
- Dheeraj Rai
- Population Health Sciences, University of Bristol, Bristol, UK.
- NIHR Bristol Biomedical Research Centre, Bristol, UK.
- Avon & Wiltshire Partnership Mental Health NHS Trust, Bath, UK.
| | - Doug Webb
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Amanda Lewis
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Leonora Cotton
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Jade Eloise Norris
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Regi Alexander
- Hertfordshire Partnership NHS Foundation Trust, Hatfield, UK
| | - David S Baldwin
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | | | - Madeleine Cochrane
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | | | - Emma J Glasson
- Telethon Kids Institute, The University of Western Australia, Perth, Australia
- Discipline of Psychiatry, Medical School, The University of Western Australia, Perth, Australia
| | - Katherine K Hatch
- Discipline of Psychiatry, Medical School, The University of Western Australia, Perth, Australia
| | - David Kessler
- Population Health Sciences, University of Bristol, Bristol, UK
- NIHR Bristol Biomedical Research Centre, Bristol, UK
| | - Peter E Langdon
- Centre for Research in Intellectual and Developmental Disabilities, University of Warwick, Coventry, UK
- Coventry and Warwickshire Partnership NHS Trust, Coventry, UK
| | - Helen Leonard
- Telethon Kids Institute, The University of Western Australia, Perth, Australia
- Discipline of Psychiatry, Medical School, The University of Western Australia, Perth, Australia
| | - Stephanie J MacNeill
- Population Health Sciences, University of Bristol, Bristol, UK
- NIHR Bristol Biomedical Research Centre, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Nicola Mills
- Population Health Sciences, University of Bristol, Bristol, UK
- NIHR Bristol Biomedical Research Centre, Bristol, UK
| | - Maximiliano Vazquez Morales
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | | | - Raja Mukherjee
- Surrey and Borders Partnership NHS Foundation Trust, Leatherhead, UK
| | - Alba X Realpe
- Population Health Sciences, University of Bristol, Bristol, UK
- NIHR Bristol Biomedical Research Centre, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Ailsa Russell
- Centre for Applied Autism Research, Department of Psychology, University of Bath, Bath, UK
| | - Sergio Starkstein
- Discipline of Psychiatry, Medical School, The University of Western Australia, Perth, Australia
| | - Jodi Taylor
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Nicholas Turner
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Joanna Thorn
- Population Health Sciences, University of Bristol, Bristol, UK
- Bristol Trials Centre, University of Bristol, Bristol, UK
| | - Jack Welch
- Dorset County Hospital NHS Foundation Trust, Dorchester, UK
| | - Nicola Wiles
- Population Health Sciences, University of Bristol, Bristol, UK
- NIHR Bristol Biomedical Research Centre, Bristol, UK
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14
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Kandola A, Edwards K, Muller MAE, Dührkoop B, Hein B, Straatman J, Hayes JF. Digitally managing depression: A fully remote randomised attention-placebo controlled trial. Digit Health 2024; 10:20552076241260409. [PMID: 38854919 PMCID: PMC11162123 DOI: 10.1177/20552076241260409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2024] [Indexed: 06/11/2024] Open
Abstract
Background Depression is a common and disabling condition. Digital apps may augment or facilitate care, particularly in under-served populations. We tested the efficacy of juli, a digital self-management app for depression in a fully remote randomised controlled trial. Methods A pragmatic randomised controlled trial that included participants aged > 18 who self-identified as having depression and scored > 5 on the Patient Health Questionnaire-8. Participants were randomly assigned (1:1) to receive juli for 8 weeks or a limited attention-placebo control app. Our primary outcome was the difference in Patient Health Questionnaire-8 scores at 8 weeks. Secondary outcomes were remission, minimal clinically important difference, worsening of depression, and health-related quality of life. Analyses were per-protocol (primary), and modified and full intention-to-treat (secondary). The trial was registered at ISRCTN (ISRCTN12329547). Results Between May 2021 and January 2023, we randomised 908 participants. 662 completed the week 2 outcome assessment and were included in the modified intention-to-treat analysis, and 456 completed the week 8 outcome assessments (per-protocol). In the per-protocol analysis, the juli group had a greater reduction in Patient Health Questionnaire-8 score (10.78, standard deviation 6.26) than the control group (11.88, standard deviation 5.73) by week 8 (baseline adjusted β-coefficient -0.94, 95% CI: -1.87 to -0.22, p = 0.045). Achieving remission and a minimal clinically important difference was more likely in the juli group at 8 weeks (adjusted odds ratios 2.22, 95% CI: 1.45-3.39, p < 0.001 and 1.56, 95% CI: 1.08-2.27, p = 0.018, respectively). There were no between-group differences in health-related quality of life or worsening of depression. Modified and full intention-to-treat analyses found similar results, but the primary outcome was non-significant. Conclusion The use of juli for 8 weeks resulted in a small reduction in symptoms of depression compared with an attention-placebo control. The juli app is a digital self-management tool that could increase the accessibility of evidence-based depression treatments.
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Affiliation(s)
- Aaron Kandola
- MRC Unit of Lifelong Health and Aging, University College London - UCL, UK
- juli Health, Hull, MA, USA
| | - Kyra Edwards
- Division of Psychiatry, University College London - UCL, UK
| | | | | | | | | | - Joseph F Hayes
- juli Health, Hull, MA, USA
- Division of Psychiatry, University College London - UCL, UK
- Camden and Islington NHS Foundation Trust, London, UK
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15
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Patil AS, Koul S. Role of Biosynthesis and Catabolism of Neurotransmitters in Drug Discovery for Anxiety and Depression. Curr Pharm Des 2024; 30:2587-2596. [PMID: 39075953 DOI: 10.2174/0113816128309913240704095334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/23/2024] [Accepted: 06/03/2024] [Indexed: 07/31/2024]
Abstract
The purpose of this review is to correlate the probable causes of anxiety disorders with the imbalance of neurotransmitters in the brain and also highlight the drugs for these mental disorders that have been discovered based on the biosynthesis and catabolism of these brain chemicals. Peer-reviewed journal's articles, news and books published in English between 1997 and 2023 describing the role of neurotransmitters in anxiety disorders were searched in Google Scholar, Research Gate and PubMed databases. The contents were carefully analyzed by the authors and understood and compiled to build a concise perspective on the role of biosynthesis and catabolism of neurotransmitters in anxiety and depression. Anxiety disorders are reported to be common patterns of psychological symptoms that impact multiple areas of life. Anxiety and depression are prevalent worldwide and are significantly contributing towards the global health burden. Genetic determinants are believed to play an important role in these disorders. According to modern medicine, one of the most important aspects that is known to be crucial for these disorders is the imbalance of neurotransmitters in the brain. The biosynthesis and catabolism of neurotransmitters have been extensively targeted for innovative drug discovery approaches at various steps that have led to the discovery of many drugs for these psychological disorders. The biosynthetic and catabolic reaction cycles of neurotransmitters and the discovery of drugs based on these hypotheses are discussed. To the best of the authors' knowledge, this review compiles already known descriptive knowledge on "relation of neurotransmitter imbalance with anxiety disorders" in a precise way that will provide readers with an overview of the vast literature.
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Affiliation(s)
- Ashish Suresh Patil
- School of Consciousness, Dr. Vishwanath Karad MIT World Peace University, Kothrud, Pune, Maharashtra, 411038, India
| | - Summon Koul
- School of Consciousness, Dr. Vishwanath Karad MIT World Peace University, Kothrud, Pune, Maharashtra, 411038, India
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16
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Payet JM, Stevens L, Russo AM, Jaehne EJ, van den Buuse M, Kent S, Lowry CA, Baratta MV, Hale MW. The Role of Dorsal Raphe Nucleus Serotonergic Systems in Emotional Learning and Memory in Male BALB/c Mice. Neuroscience 2023; 534:1-15. [PMID: 37852412 DOI: 10.1016/j.neuroscience.2023.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/04/2023] [Accepted: 10/06/2023] [Indexed: 10/20/2023]
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for a variety of anxiety-, trauma- and stressor-related disorders. Although they are efficacious, therapeutic improvements require several weeks of treatment and are often associated with an initial exacerbation of symptoms. The dorsal raphe nucleus (DR) has been proposed as an important target for the modulation of emotional responses and the therapeutic effects of SSRIs. Using a fear-conditioning paradigm we aimed to understand how SSRIs affect emotional learning and memory, and their effects on serotonergic circuitry. Adult male BALB/c mice were treated with vehicle (n = 16) or the SSRI fluoxetine (18 mg/kg/d) acutely (n = 16), or chronically (21d, n = 16), prior to fear conditioning. Treatment was stopped, and half of the mice (n = 8/treatment group) were exposed to cued fear memory recall 72 h later. Activation of DR serotonergic neurons during fear conditioning (Experiment 1) or fear memory recall (Experiment 2), was measured using dual-label immunohistochemistry for Tph2 and c-Fos. Acute and chronic fluoxetine treatment reduced associative fear learning without affecting memory recall and had opposite effects on anxiety-like behaviour. Acute fluoxetine decreased serotonergic activity in the DR, while chronic treatment led to serotonergic activity that was indistinguishable from that of control levels in DRD and DRV subpopulations. Chronic fluoxetine facilitated fear extinction, which was associated with rostral DRD inhibition. These findings provide further evidence that SSRIs can alter aspects of learning and memory processes and are consistent with a role for discrete populations of DR serotonergic neurons in regulating fear- and anxiety-related behaviours.
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Affiliation(s)
- Jennyfer M Payet
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia
| | - Laura Stevens
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia
| | - Adrian M Russo
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia
| | - Emily J Jaehne
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia; Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
| | - Maarten van den Buuse
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia
| | - Stephen Kent
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia
| | - Christopher A Lowry
- Department of Integrative Physiology and Centre for Neuroscience, University of Colorado Boulder, Boulder, Colorado, USA
| | - Michael V Baratta
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado, USA
| | - Matthew W Hale
- Department of Psychology, Counselling and Therapy, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia.
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17
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Ishrat Husain M, Rodie DJ, Perivolaris A, Sanches M, Crawford A, Fitzgibbon KP, Levinson A, Geist R, Kurdyak P, Mitchell B, Oslin D, Sunderji N, Mulsant BH, for the PARTNERs Study Group. A Collaborative-Care Telephone-Based Intervention for Depression, Anxiety, and at-Risk Drinking in Primary Care: The PARTNERs Randomized Clinical Trial. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2023; 68:732-744. [PMID: 36855791 PMCID: PMC10517649 DOI: 10.1177/07067437231156243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
BACKGROUND Collaborative care (CC) could improve outcomes in primary care patients with common mental conditions. We assessed the effectiveness of a transdiagnostic model of telephone-based CC (tCC) delivered by lay providers to primary care patients with depression, anxiety, or at-risk drinking. METHODS PARTNERS was a pragmatic trial in 502 primary care adults presenting with depressive symptoms, anxiety symptoms, or at-risk drinking randomized to (1) usual care by primary care providers (PCPs) enhanced with the results of computer-assisted telephone-based assessments (at baseline and 4, 8, and 12 months later) (enhanced usual care [eUC]) or (2) tCC consisting of eUC plus frequent telephone coaching and psychoeducation provided by mental health technicians who also communicated to the PCP recommendations from a psychiatrist for evidence-based pharmacotherapy, psychotherapy, or, when indicated, referrals to mental health services. The primary analysis compared the change on the 9-item Patient Health Questionnaire (PHQ-9) in participants presenting with depression (n = 366) randomized to tCC versus eUC. Secondary analyses compared changes on the Generalized Anxiety Disorder-7 scale (GAD-7) in those presenting with anxiety (n = 298); or change in the number of weekly drinks in those presenting with at-risk drinking (n = 176). RESULTS There were no treatment or time×treatment effects between tCC and eUC on PHQ-9 scores for patients with depression during the 12-month follow-up. However, there was a treatment effect (tCC > eUC) on GAD-7 scores in those with anxiety and a time×treatment interaction effect on the number of weekly drinks (tCC > eUC) in those with at-risk drinking. CONCLUSION Implementing transdiagnostic tCC for common mental disorders using lay providers appears feasible in Canadian primary care. While tCC was not better than eUC for depression, there were some benefits for those with anxiety or at-risk drinking. Future studies will need to confirm whether tCC differentially benefits patients with depression, anxiety, or at-risk drinking.
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Affiliation(s)
- M. Ishrat Husain
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - David J. Rodie
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | | | - Marcos Sanches
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Allison Crawford
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | | | - Andrea Levinson
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Rose Geist
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Hospital for Sick Children, Toronto, ON, Canada
| | - Paul Kurdyak
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | | | - David Oslin
- Department of Psychiatry, University of Pennsylvania and the Department of Veteran Affairs, Philadelphia, PA, USA
| | - Nadiya Sunderji
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Waypoint Centre for Mental Health Care, Penetanguishene, ON, Canada
| | - Benoit H. Mulsant
- Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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18
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Landrø NI, Harmer CJ, Blackwell SE, Bø R, Dawson G, Goodwin G, Hagen HS, Kingslake J, Klovning A, Klungsøyr O, Schjøtt-Pedersen O, Sæther AK, Torgersen KS, Vaaler A, Andreassen OA, Røssberg JI. Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial. Contemp Clin Trials 2023; 133:107326. [PMID: 37652355 DOI: 10.1016/j.cct.2023.107326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 08/18/2023] [Accepted: 08/28/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. METHODS A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). DISCUSSION The clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.
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Affiliation(s)
- Nils Inge Landrø
- Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Norway.
| | - Catherine J Harmer
- Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Norway; Department of Psychiatry, Oxford University, UK; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford OX3 7JX, UK
| | - Simon E Blackwell
- Mental Health Research and Treatment Centre, Department of Psychology, Ruhr-Universität Bochum, Germany
| | - Ragnhild Bø
- Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Norway
| | | | | | | | | | - Atle Klovning
- Department of General Practice, Institute of Health and Society, University of Oslo, Norway
| | - Ole Klungsøyr
- Institute of Clinical Medicine, University of Oslo, Norway
| | | | | | | | - Arne Vaaler
- Department of Acute Psychiatry, St Olavs Hospital, Trondheim, Norway; Department of Mental Health, Faculty of Medicine, Norwegian University of Science and Technology, Norway
| | - Ole A Andreassen
- Institute of Clinical Medicine, University of Oslo, Norway; NORMENT Centre, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Norway
| | - Jan Ivar Røssberg
- Institute of Clinical Medicine, University of Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Norway
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Dahle NE, Matthew C, Roskvist RP, Moir F, Arroll B. Emoqol-100: Development and validation of a single question for low mood in primary care. A retrospective audit. BJGP Open 2023; 7:BJGPO.2023.0011. [PMID: 37160336 PMCID: PMC10646210 DOI: 10.3399/bjgpo.2023.0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/21/2023] [Accepted: 04/25/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Patients with depression need to be diagnosed and managed effectively in primary care. However, current inventories for case-finding low mood are time-consuming when considering the limited time available during appointments. AIM To validate the diagnostic accuracy of a single question on the emotional quality of life (Emoqol-100) as a measure of depression in symptomatic patients. DESIGN & SETTING A retrospective clinical audit, validating the Emoqol-100 compared with the 9-item Patient Health Questionnaire (PHQ-9) and Burns Depression Scale Today (BDST) in South Auckland, New Zealand. METHOD Consecutive patients with suspected low mood, seen over 22 months in a single primary care clinic by one of the authors, were eligible for this retrospective audit (n = 160). The index test was the verbally asked Emoqol-100: 'How is your emotional quality of life now, with 100 being perfect and 0 being the worst imaginable?' The reference standard was the PHQ-9 (n = 426 visits) with a cut-off point of ≥10 or BDST (n = 513 visits) with a cut-off point of ≥6. RESULTS The Emoqol-100 range 0-20 had a likelihood ratio (LR) of 25.2 for low mood compared with the BDST as the reference standard; and for Emoqol-100 scores of 21-40, 41-60, 61-80, and 81-100 the LRs were 3.6, 1.7, 0.35, and 0.09, respectively. For the PHQ-9, these were 10.1, 2.9, 1.3, 0.40, and 0.2, respectively. Any score ≤60 was associated with a low mood. CONCLUSION The Emoqol-100 appears to have high validity, so when it is low (≤60), it is suggestive of a high PHQ-9 or BDST score, and a mood issue probably exists. Emoqol-100 could be helpful for busy primary care professionals and other clinicians.
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Affiliation(s)
- Nina Edel Dahle
- Centre for Clinical Research, Uppsala University, Falun, Sweden
- Primary Health Care Center Britsarvet-Grycksbo, County of Dalarna, Falun, Sweden
| | - Carolyn Matthew
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | | | - Fiona Moir
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | - Bruce Arroll
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
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20
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Jiang X, Zheng H, Yang R, Wang S, Zhong H. Retrospective analysis of clinical characteristics and treatment of children and adolescents with depression. Front Psychiatry 2023; 14:1036314. [PMID: 37575578 PMCID: PMC10412874 DOI: 10.3389/fpsyt.2023.1036314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 05/29/2023] [Indexed: 08/15/2023] Open
Abstract
Objective To analyze the demographic and clinical characteristics and treatment among children and adolescents with depression in different age groups of onset. Methods 635 children and adolescents with depression in a hospital from January 2014 to December 2021 were collected by e-case, and grouped according to age of onset, including 115 cases in childhood 8-12, 359 cases in early adolescence 13-1 and 161 cases in late adolescence 16-18, and the general conditions, clinical characteristics, and treatment were compared between the three groups. Results Females had more onset and were more likely to have psychotic symptoms in childhood, short duration and hospitalization in early adolescence increased year by year, and males had more onset and less hospitalization in late adolescence. There were no statistical differences in medication regimen, suicide, length of hospitalization, or family history between the three groups. Conclusion Children and adolescents with depression have their unique clinical characteristics at different age of onset and need to enhance prevention and individualized treatment.
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Affiliation(s)
- Xiaolu Jiang
- Department of Child and Adolescents, Affiliated Psychological Hospital of Anhui Medical University, Hefei, Anhui, China
| | | | - Rong Yang
- School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, China
| | - Shuo Wang
- School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, China
| | - Hui Zhong
- Department of Child and Adolescents, Affiliated Psychological Hospital of Anhui Medical University, Hefei, Anhui, China
- Department of Child and Adolescents, Fourth People’s Hospital, Hefei, Anhui, China
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21
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Smith EG, Grigorian HL. A System for Rapidly Yet Rigorously Evaluating the Quality of Randomized Controlled Trials. J Clin Psychopharmacol 2023; 43:306-312. [PMID: 37378832 DOI: 10.1097/jcp.0000000000001724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
ABSTRACT This tutorial describes a system for rapidly yet rigorously assessing the quality of randomized controlled trials (RCTs). The system has 7 criteria, represented by the acronym "BIS FOES." The BIS FOES system directs readers to assess RCTs based on the following 7 criteria: the RCT's use (or not) of effective (1) Blinding; the RCT's use (or not) of (2) Intent-to-Treat Analysis; the RCT's (3) Size and other information reflecting the effectiveness of randomization; the amount of sample lost during (4) Follow-up; the (5) Outcomes examined by the RCT (specifically, the outcome measures used by the RCT), the (6) Effects reported (ie, the statistical and clinical significance of the RCT's primary, secondary, and safety findings), and any (7) Special Considerations (ie, additional strengths, limitations, or notable features of the RCT). The first 6 criteria are of basic importance to the assessment of every RCT, whereas the Special Considerations criteria allows the system to be expanded to include virtually any other important aspect of the RCT. This tutorial explains the importance of these criteria and how to assess them. This tutorial also describes how many BIS FOES criteria can be initially assessed from the RCT Abstract while also directing readers to specific locations in the RCT article where additional important information can be found. We hope that the BIS FOES system will help healthcare trainees, but also potentially clinicians, researchers, and the general public, rapidly and thoroughly assess RCTs.
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22
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Arroll B, Roskvist R, Moir F, Harwood M, Eggleton K, Dowrick C, Cuijpers P. Antidepressants in primary care: limited value at the first visit. World Psychiatry 2023; 22:340. [PMID: 37159355 PMCID: PMC10168160 DOI: 10.1002/wps.21057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/11/2023] Open
Affiliation(s)
- Bruce Arroll
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | - Rachel Roskvist
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | - Fiona Moir
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | - Matire Harwood
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | - Kyle Eggleton
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
| | - Christopher Dowrick
- Department of Primary Care and Mental Health, University of Liverpool, Liverpool, UK
| | - Pim Cuijpers
- Department of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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23
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Gan SL, Long YQ, Wang QY, Feng CD, Lai CX, Liu CT, Ding YY, Liu H, Peng K, Ji FH. Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial. Front Psychiatry 2023; 14:1128406. [PMID: 37009103 PMCID: PMC10050377 DOI: 10.3389/fpsyt.2023.1128406] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/23/2023] [Indexed: 03/17/2023] Open
Abstract
BackgroundDepressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery.MethodsIn this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality.Main resultsA total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = −10.5, 95%CI = −19.6% to −0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = −10.8, 95%CI = −20.2% to −0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001).ConclusionPerioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).
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Affiliation(s)
- Shu-lin Gan
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Yu-qin Long
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Qin-yun Wang
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Chang-dong Feng
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Chen-xu Lai
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Chun-tong Liu
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Yun-ying Ding
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
| | - Hong Liu
- Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, United States
| | - Ke Peng
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
- *Correspondence: Ke Peng,
| | - Fu-hai Ji
- Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, China
- Fu-hai Ji,
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von Mücke-Heim IA, Urbina-Treviño L, Bordes J, Ries C, Schmidt MV, Deussing JM. Introducing a depression-like syndrome for translational neuropsychiatry: a plea for taxonomical validity and improved comparability between humans and mice. Mol Psychiatry 2023; 28:329-340. [PMID: 36104436 PMCID: PMC9812782 DOI: 10.1038/s41380-022-01762-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 08/09/2022] [Accepted: 08/18/2022] [Indexed: 01/11/2023]
Abstract
Depressive disorders are the most burdensome psychiatric disorders worldwide. Although huge efforts have been made to advance treatment, outcomes remain unsatisfactory. Many factors contribute to this gridlock including suboptimal animal models. Especially limited study comparability and replicability due to imprecise terminology concerning depressive-like states are major problems. To overcome these issues, new approaches are needed. Here, we introduce a taxonomical concept for modelling depression in laboratory mice, which we call depression-like syndrome (DLS). It hinges on growing evidence suggesting that mice possess advanced socioemotional abilities and can display non-random symptom patterns indicative of an evolutionary conserved disorder-like phenotype. The DLS approach uses a combined heuristic method based on clinical depression criteria and the Research Domain Criteria to provide a biobehavioural reference syndrome for preclinical rodent models of depression. The DLS criteria are based on available, species-specific evidence and are as follows: (I) minimum duration of phenotype, (II) significant sociofunctional impairment, (III) core biological features, (IV) necessary depressive-like symptoms. To assess DLS presence and severity, we have designed an algorithm to ensure statistical and biological relevance of findings. The algorithm uses a minimum combined threshold for statistical significance and effect size (p value ≤ 0.05 plus moderate effect size) for each DLS criterion. Taken together, the DLS is a novel, biologically founded, and species-specific minimum threshold approach. Its long-term objective is to gradually develop into an inter-model validation standard and microframework to improve phenotyping methodology in translational research.
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Affiliation(s)
- Iven-Alex von Mücke-Heim
- grid.419548.50000 0000 9497 5095Max Planck Institute of Psychiatry, Molecular Neurogenetics, Munich, Germany ,grid.419548.50000 0000 9497 5095Department of Translational Research, Max Planck Institute of Psychiatry, Munich, Germany ,grid.4372.20000 0001 2105 1091International Max Planck Research School for Translational Psychiatry, Munich, Germany
| | - Lidia Urbina-Treviño
- grid.419548.50000 0000 9497 5095Max Planck Institute of Psychiatry, Molecular Neurogenetics, Munich, Germany
| | - Joeri Bordes
- grid.4372.20000 0001 2105 1091International Max Planck Research School for Translational Psychiatry, Munich, Germany ,grid.419548.50000 0000 9497 5095Max Planck Institute of Psychiatry, Neurobiology of Stress Resilience, Munich, Germany
| | - Clemens Ries
- grid.419548.50000 0000 9497 5095Max Planck Institute of Psychiatry, Molecular Neurogenetics, Munich, Germany ,grid.4372.20000 0001 2105 1091International Max Planck Research School for Translational Psychiatry, Munich, Germany
| | - Mathias V. Schmidt
- grid.419548.50000 0000 9497 5095Max Planck Institute of Psychiatry, Neurobiology of Stress Resilience, Munich, Germany
| | - Jan M. Deussing
- grid.419548.50000 0000 9497 5095Max Planck Institute of Psychiatry, Molecular Neurogenetics, Munich, Germany
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Ahmed N, Bone JK, Lewis G, Freemantle N, Harmer CJ, Duffy L, Lewis G. The effect of sertraline on emotional processing: secondary analyses of the PANDA randomised controlled trial. Psychol Med 2022; 52:2814-2821. [PMID: 33431087 PMCID: PMC9647512 DOI: 10.1017/s0033291720004985] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 10/29/2020] [Accepted: 11/30/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND According to the cognitive neuropsychological model, antidepressants reduce symptoms of depression and anxiety by increasing positive relative to negative information processing. Most studies of whether antidepressants alter emotional processing use small samples of healthy individuals, which lead to low statistical power and selection bias and are difficult to generalise to clinical practice. We tested whether the selective serotonin reuptake inhibitor (SSRI) sertraline altered recall of positive and negative information in a large randomised controlled trial (RCT) of patients with depressive symptoms recruited from primary care. METHODS The PANDA trial was a pragmatic multicentre double-blind RCT comparing sertraline with placebo. Memory for personality descriptors was tested at baseline and 2 and 6 weeks after randomisation using a computerised emotional categorisation task followed by a free recall. We measured the number of positive and negative words correctly recalled (hits). Poisson mixed models were used to analyse longitudinal associations between treatment allocation and hits. RESULTS A total of 576 participants (88% of those randomised) completed the recall task at 2 and 6 weeks. We found no evidence that positive or negative hits differed according to treatment allocation at 2 or 6 weeks (adjusted positive hits ratio = 0.97, 95% CI 0.90-1.05, p = 0.52; adjusted negative hits ratio = 0.99, 95% CI 0.90-1.08, p = 0.76). CONCLUSIONS In the largest individual placebo-controlled trial of an antidepressant not funded by the pharmaceutical industry, we found no evidence that sertraline altered positive or negative recall early in treatment. These findings challenge some assumptions of the cognitive neuropsychological model of antidepressant action.
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Affiliation(s)
- Norin Ahmed
- Division of Psychiatry, University College London, Faculty of Brain Sciences, London, UK
| | - Jessica K. Bone
- Division of Psychiatry, University College London, Faculty of Brain Sciences, London, UK
| | - Gemma Lewis
- Division of Psychiatry, University College London, Faculty of Brain Sciences, London, UK
| | - Nick Freemantle
- Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Catherine J. Harmer
- University Department of Psychiatry, Warneford Hospital, Oxford, UK
- Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK
| | - Larisa Duffy
- Division of Psychiatry, University College London, Faculty of Brain Sciences, London, UK
| | - Glyn Lewis
- Division of Psychiatry, University College London, Faculty of Brain Sciences, London, UK
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26
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Hobbs C, Beck M, Denham F, Pettitt L, Faraway J, Munafò MR, Sui J, Kessler D, Button KS. Relationship between change in social evaluation learning and mood in early antidepressant treatment: A prospective cohort study in primary care. J Psychopharmacol 2022; 37:303-312. [PMID: 36000259 PMCID: PMC10076340 DOI: 10.1177/02698811221116928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Antidepressants are proposed to work by increasing sensitivity to positive versus negative information. Increasing positive affective learning within social contexts may help remediate negative self-schema. We investigated the association between change in biased learning of social evaluations about the self and others, and mood during early antidepressant treatment. METHOD Prospective cohort assessing patients recruited from primary care in South West England at four timepoints over the first 8 weeks of antidepressant treatment (n = 29). At each timepoint, participants completed self-report measures of depression (Beck Depression Inventory II (BDI-II) and Patient Health Questionnaire 9 (PHQ-9)), anxiety (Generalised Anxiety Disorder Questionnaire 7 (GAD-7)), and a computerised task measuring learning of social evaluations about the self, a friend and a stranger. RESULTS We did not find evidence that learning about the self was associated with a reduction in PHQ-9 (b = 0.08, 95% CI: -0.05, 0.20, p = 0.239) or BDI-II scores (b = 0.10, 95% CI: -0.18, 0.38, p = 0.469). We found some weak evidence that increased positive learning about the friend was associated with a reduction in BDI-II scores (b = 0.30, 95% CI: -0.02, 0.62, p = 0.069). However, exploratory analyses indicated stronger evidence that increased positive learning about the self (b = 0.18, 95% CI: 0.07, 0.28, p = 0.002) and a friend (b = 0.22, 95% CI: 0.10, 0.35, p = 0.001) was associated with reductions in anxiety. CONCLUSIONS Change in social evaluation learning was associated with a reduction in anxiety but not depression. Antidepressants may treat anxiety symptoms by remediating negative affective biases towards socially threatening information directed towards the self and close others. However, our findings are based on exploratory analyses within a small sample without a control group and are therefore at risk of type 1 errors and order effects. Further research with larger samples is required.
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Affiliation(s)
| | - Milly Beck
- Department of Psychology, University of Bath, Bath, UK
| | - Faye Denham
- Department of Psychology, University of Bath, Bath, UK
| | - Laura Pettitt
- Department of Psychology, University of Bath, Bath, UK
| | - Julian Faraway
- Department of Mathematical Sciences, University of Bath, Bath, UK
| | - Marcus R Munafò
- School of Psychological Science, University of Bristol, Bristol, UK.,MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.,National Institute of Health Research Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK
| | - Jie Sui
- School of Psychology, University of Aberdeen, Aberdeen, UK
| | - David Kessler
- Population Health Sciences, University of Bristol, Bristol, UK
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Lin YH, Sahker E, Shinohara K, Horinouchi N, Ito M, Lelliott M, Cipriani A, Tomlinson A, Baethge C, Furukawa TA. Assessment of blinding in randomized controlled trials of antidepressants for depressive disorders 2000-2020: A systematic review and meta-analysis. EClinicalMedicine 2022; 50:101505. [PMID: 35812993 PMCID: PMC9257339 DOI: 10.1016/j.eclinm.2022.101505] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 05/23/2022] [Accepted: 05/23/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND In double-blind randomized controlled trials (RCTs) of antidepressants, blinding can be broken due to the apparent side effects, and unsuccessful blinding can lead to overestimation of effect sizes. New generation antidepressants with less severe side effects may be less susceptible to broken blinding. However, successfulness of blinding in new generation antidepressant trials and its influence on trial effect size estimates remain unclear. METHODS Extending a previous systematic review assessing blinding successfulness in psychiatric trials (2000-2010), we searched PubMed/Medline for double-blinded antidepressant RCTs (2010-2020) for trials assessing blinding success. Our primary outcome was the degree of blinding successfulness, measured as kappa statistics between guesses and true allocations. We used random-effects meta-analysis to synthesize studies. We used meta-regression and Pearson's r to examine the relationship between blinding success and effect sizes. This study is registered with PROSPERO (CRD42021249973). FINDINGS Among 154 eligible studies, 11 (7·1%) contained information on blinding assessment between 2010 and 2020. Five studies were added from the previous review, and altogether nine of the 16 studies provided usable data. Agreement in individual studies ranged from κ=-0·14 to 0·38. The summary agreement between guesses and the truth was 0·21 (95% CI: 0·14 to 0·28) among patients and 0·17 (95% CI: 0·05 to 0·30) among assessors. Blinding success was not associated with effect size (patients: r = 0·37, p = 0·32; assessors: r = 0·28; p = 0·72). Meta-regression also failed to find a significant relationship between blinding success and depression effect sizes (β=0·06, p = 0·09). INTERPRETATION Less than 10% of the antidepressant RCTs reported blinding assessment. The results in new generation antidepressant trials indicated that patients and assessors were unlikely to be able to judge treatment allocation. There was little evidence that the extent of unblinding biased the effect size estimates of new generation antidepressants. FUNDING None.
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Affiliation(s)
- Yi-Hsuan Lin
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
| | - Ethan Sahker
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
- Population Health and Policy Research Unit, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kiyomi Shinohara
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
| | - Noboru Horinouchi
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
| | - Masami Ito
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
| | - Madoka Lelliott
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
| | - Andrea Cipriani
- Department of Psychiatry, University of Oxford, Oxford, UK
- Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK
| | - Anneka Tomlinson
- Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK
| | - Christopher Baethge
- Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany
| | - Toshi A. Furukawa
- Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan
- Corresponding author at: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
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28
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Kounali D, Button KS, Lewis G, Gilbody S, Kessler D, Araya R, Duffy L, Lanham P, Peters TJ, Wiles N, Lewis G. How much change is enough? Evidence from a longitudinal study on depression in UK primary care. Psychol Med 2022; 52:1875-1882. [PMID: 33138872 PMCID: PMC9340848 DOI: 10.1017/s0033291720003700] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 07/03/2020] [Accepted: 07/20/2020] [Indexed: 11/07/2022]
Abstract
BACKGROUND The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists. METHODS A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a 'global rating of change' scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R). RESULTS For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) -26.7 to -14.9) on the PHQ-9; 23% (95% CI -27.8 to -18.0) on the BDI-II and 26.8% (95% CI -33.5 to -20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were -1.7, -3.5 and -1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement. CONCLUSIONS An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit. FUNDING Funding. National Institute for Health Research.
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Affiliation(s)
- Daphne Kounali
- Bristol Medical School, University of Bristol, Bristol, UK
| | | | - Gemma Lewis
- Division of Psychiatry, University College London, London, UK
| | - Simon Gilbody
- Department of Health Sciences, University of York, York, UK
| | - David Kessler
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Ricardo Araya
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Larisa Duffy
- Division of Psychiatry, University College London, London, UK
| | - Paul Lanham
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Tim J. Peters
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Nicola Wiles
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Glyn Lewis
- Division of Psychiatry, University College London, London, UK
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Lee SY, Wang LJ, Yang YH, Hsu CW. The comparative effectiveness of antidepressants for youths with major depressive disorder: a nationwide population-based study in Taiwan. Ther Adv Chronic Dis 2022; 13:20406223221098114. [PMID: 35634571 PMCID: PMC9131383 DOI: 10.1177/20406223221098114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 04/14/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Guidelines recommend fluoxetine as a first-line medication for youths diagnosed with major depressive disorder (MDD). However, little is known about the long-term effectiveness of different antidepressants in juveniles in the real world. This study aimed to compare the effectiveness of antidepressants in youths with MDD. Methods: Youths (<20 years old) with a diagnosis of MDD who were new users of antidepressants were selected from a nationwide population-based cohort in Taiwan between 1997 and 2013. We divided a total of 16,981 users (39.9% male; mean age: 16.6 years) into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, venlafaxine, citalopram, escitalopram, bupropion, fluvoxamine, mirtazapine and moclobemide). Regarding treatment outcomes (hospitalisation and medication discontinuation), Cox proportional hazards regression models were applied to estimate the hazards of such outcomes. Results: Compared with the youths treated with fluoxetine, the bupropion-treated group demonstrated lower rates of hospitalisation and discontinuation. Mirtazapine-treated group demonstrated a higher hospitalisation risk mainly when administered for single depressive episodes. Furthermore, patients treated with sertraline and fluvoxamine had higher discontinuation rates. Among the younger teenage subgroups (< 16 years), significantly higher rates of discontinuation were observed in those treated with sertraline, escitalopram and fluvoxamine. Among the older teenage subgroups (⩾ 16 years), bupropion was superior to fluoxetine in preventing hospitalisation and discontinuation. Conclusion: We concluded that bupropion might surpass fluoxetine with regard to hospitalisation prevention and drug therapy maintenance among youths with MDD, while mirtazapine users demonstrated a higher hospitalisation risk. Our findings might serve as a reference for clinicians in future studies.
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Affiliation(s)
- Sheng-Yu Lee
- Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung
- Department of Psychiatry, College of Medicine, Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yao-Hsu Yang
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi County
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi County
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan
| | - Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niaosong District, Kaohsiung 83301
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan
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30
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Buckman JEJ, Saunders R, Stott J, Cohen ZD, Arundell LL, Eley TC, Hollon SD, Kendrick T, Ambler G, Watkins E, Gilbody S, Kessler D, Wiles N, Richards D, Brabyn S, Littlewood E, DeRubeis RJ, Lewis G, Pilling S. Socioeconomic Indicators of Treatment Prognosis for Adults With Depression: A Systematic Review and Individual Patient Data Meta-analysis. JAMA Psychiatry 2022; 79:406-416. [PMID: 35262620 PMCID: PMC8908224 DOI: 10.1001/jamapsychiatry.2022.0100] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression. Objective To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis for adults treated for depression in primary care, independent of treatment and after accounting for clinical prognostic factors. Data Sources The Embase, International Pharmaceutical Abstracts, MEDLINE, PsycINFO, and Cochrane (CENTRAL) databases were searched from database inception to October 8, 2021. Study Selection Inclusion criteria were as follows: randomized clinical trials that used the Revised Clinical Interview Schedule (CIS-R; the most common comprehensive screening and diagnostic measure of depressive and anxiety symptoms in primary care randomized clinical trials), measured socioeconomic factors at baseline, and sampled patients with unipolar depression who sought treatment for depression from general physicians/practitioners or who scored 12 or more points on the CIS-R. Exclusion criteria included patients with depression secondary to a personality or psychotic disorder or neurologic condition, studies of bipolar or psychotic depression, studies that included children or adolescents, and feasibility studies. Studies were independently assessed against inclusion and exclusion criteria by 2 reviewers. Data Extraction and Synthesis Data were extracted and cleaned by data managers for each included study, further cleaned by multiple reviewers, and cross-checked by study chief investigators. Risk of bias and quality were assessed using the Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Individual Participant Data (PRISMA-IPD) reporting guidelines. Main Outcomes and Measures Depressive symptoms at 3 to 4 months after baseline. Results This systematic review and individual patient data meta-analysis identified 9 eligible studies that provided individual patient data for 4864 patients (mean [SD] age, 42.5 (14.0) years; 3279 women [67.4%]). The 2-stage random-effects meta-analysis end point depressive symptom scale scores were 28% (95% CI, 20%-36%) higher for unemployed patients than for employed patients and 18% (95% CI, 6%-30%) lower for patients who were homeowners than for patients living with family or friends, in hostels, or homeless, which were equivalent to 4.2 points (95% CI, 3.6-6.2 points) and 2.9 points (95% CI, 1.1-4.9 points) on the Beck Depression Inventory II, respectively. Financial strain and educational attainment were associated with prognosis independent of treatment, but unlike employment and housing status, there was little evidence of associations after adjusting for clinical prognostic factors. Conclusions and Relevance Results of this systematic review and meta-analysis revealed that unemployment was associated with a poor prognosis whereas home ownership was associated with improved prognosis. These differences were clinically important and independent of the type of treatment received. Interventions that address employment or housing difficulties could improve outcomes for patients with depression.
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Affiliation(s)
- Joshua E. J. Buckman
- Centre for Outcomes Research and Effectiveness (CORE), Research Department of Clinical, Educational & Health Psychology, University College London, London, United Kingdom
- iCope Camden & Islington NHS Foundation Trust, St Pancras Hospital, London, United Kingdom
| | - Rob Saunders
- Centre for Outcomes Research and Effectiveness (CORE), Research Department of Clinical, Educational & Health Psychology, University College London, London, United Kingdom
| | - Joshua Stott
- Centre for Outcomes Research and Effectiveness (CORE), Research Department of Clinical, Educational & Health Psychology, University College London, London, United Kingdom
| | | | - Laura-Louise Arundell
- Centre for Outcomes Research and Effectiveness (CORE), Research Department of Clinical, Educational & Health Psychology, University College London, London, United Kingdom
| | - Thalia C. Eley
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
| | - Steven D. Hollon
- Department of Psychology, Vanderbilt University, Nashville, Tennessee
| | - Tony Kendrick
- Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Gareth Ambler
- Statistical Science, University College London, London, United Kingdom
| | - Edward Watkins
- Department of Psychology, University of Exeter, Exeter, United Kingdom
| | - Simon Gilbody
- Department of Health Sciences, University of York, York, United Kingdom
| | - David Kessler
- Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Nicola Wiles
- Centre for Academic Primary Care, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - David Richards
- Institute of Health Research, University of Exeter College of Medicine and Health, Exeter, United Kingdom
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Norway
| | - Sally Brabyn
- Department of Health Sciences, University of York, York, United Kingdom
| | | | - Robert J. DeRubeis
- University of Pennsylvania College of Arts and Sciences, Department of Psychology, Philadelphia
| | - Glyn Lewis
- Division of Psychiatry, University College London, London, United Kingdom
| | - Stephen Pilling
- Centre for Outcomes Research and Effectiveness (CORE), Research Department of Clinical, Educational & Health Psychology, University College London, London, United Kingdom
- Camden & Islington NHS Foundation Trust, London, United Kingdom
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31
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Hengartner MP, Plöderl M. Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression. BMJ Evid Based Med 2022; 27:69-73. [PMID: 33593736 DOI: 10.1136/bmjebm-2020-111600] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/22/2021] [Indexed: 12/27/2022]
Abstract
The efficacy of antidepressants in the acute treatment of moderate-to-severe depression remains a controversial issue. The minimal important difference (MID) is relevant to judge the clinical significance of treatment effects. In this analysis paper, we discuss estimates of the MID for common depression outcome measures.For the Hamilton Depression Rating Scale 17-item Version (HDRS-17), according to both anchor-based and distribution-based approaches, MID estimates range from 3 to 8 points, and the most accurate values are likely between 3 and 5 points. For the 6-item version (HDRS-6), MID estimates range between 2 and 4 points. For both the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory II (BDI-II), MID estimates range between 3 and 9 points, with estimates of 3-6 points likely being the most accurate. Quality of life appears to be more important to patients than core depression symptoms. We thus also evaluated the Short-Form 36 (SF-36) mental component score, a popular mental-health-related quality of life measure. Its MID estimate is likely about 5 points. By contrast, the average treatment effects of antidepressants on the HDRS-17, HDRS-6, MADRS, BDI-II and SF-36 are 2 points, 1.5 points, 3 points, 2 points and 3-5 points, respectively.In conclusion, the efficacy of antidepressants in the acute treatment of moderate-to-severe depression consistently fails to exceed the lower bound of the MID estimates for common depression outcome measures. The clinical significance of antidepressants thus remains uncertain and we call for more research on quality of life measures, which are the patients' most valued outcome domains.
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Affiliation(s)
- Michael P Hengartner
- Department of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland
| | - Martin Plöderl
- Department of Crisis Intervention and Suicide Prevention, Paracelsus Medical University Salzburg, Salzburg, Salzburg, Austria
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32
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Liebmann EP, Resnick SG, Hoff RA, Katz IR. Interpreting patient reports of perceived change during treatment for depression: Findings from the Veterans Outcome Assessment survey. Psychiatry Res 2022; 309:114402. [PMID: 35114571 DOI: 10.1016/j.psychres.2022.114402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 01/07/2022] [Accepted: 01/15/2022] [Indexed: 11/29/2022]
Abstract
This study addressed ongoing questions about the meaning of patients' perceptions of change during treatment. The study used data from the Veterans Outcome Assessment survey for patients with a depressive disorder, without mental health comorbidities, treated in Department of Veterans Affairs general mental health clinics (n = 694). Perceived changes in problems/symptoms, other domains, and the quality of communication with providers were evaluated with items from the Experience of Care & Health Outcomes (ECHO) survey. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Linear regression models evaluated associations of perceived change at 3-months post-baseline with observed change in PHQ-9 scores, scores on other patient-reported outcome measures (PROMs), and ratings of communication with providers. Patients' reports of their clinical condition at follow-up together with ratings of communication accounted for approximately one-third of the variance in patients' perceptions of change. Adding change-scores based on baseline and follow-up scores on the PHQ-9 and other PROMs did not improve model fit. The findings suggest that patient reports of perceived change during treatment reflect their current clinical state and their experience of care more closely than actual changes in the PHQ-9 or other PROMs.
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Affiliation(s)
- Edward P Liebmann
- VA Connecticut Healthcare System, West Haven, CT, United States; Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
| | - Sandra G Resnick
- VA Office of Mental Health and Suicide Prevention, Northeast Program Evaluation Center, West Haven, CT, United States; Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
| | - Rani A Hoff
- VA Office of Mental Health and Suicide Prevention, Northeast Program Evaluation Center, West Haven, CT, United States; Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
| | - Ira R Katz
- Department of Veterans Affairs, VA Office of Mental Health and Suicide Prevention, Washington, DC, United States.
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33
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Arroll B, Frischtak H, Roskvist R, Mount V, Sundram F, Fletcher S, Kingsford DW, Buttrick L, Bricker J, van der Werf B. FACT effectiveness in primary care; a single visit RCT for depressive symptoms. Int J Psychiatry Med 2022; 57:91-102. [PMID: 33892599 DOI: 10.1177/00912174211010536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Patients with depressive symptoms are common in primary care. Brief, simple therapies are needed. AIM Is a focussed acceptance and commitment therapy (FACT) intervention more effective than the control group for patients with depressive symptoms in primary care at one week follow up?Design and setting: A randomised, blinded controlled trial at a single primary care clinic in Auckland, New Zealand. METHODS Patients presenting to their primary care practice for any reason were recruited from the clinic waiting room. Eligible patients who scored ≥2 on the PHQ-2 indicating potential depressive symptoms were randomised using a remote computer to intervention or control groups. Both groups received a psychosocial assessment using the "work-love-play" questionnaire. The intervention group received additional FACT-based behavioural activation activities. The primary outcome was the mean PHQ-8 score at one week. RESULTS 57 participants entered the trial and 52 had complete outcome data after one week. Baseline PHQ-8 scores were similar for intervention (11.0) and control (11.7). After one week, the mean PHQ-8 score was significantly lower in the intervention group (7.4 vs 10.1 for control; p<0.039 one sided and 0.078 two sided). The number needed to treat to achieve a PHQ-8 score ≤6 was 4.0 on intention to treat analysis (p = 0.043 two sided). There were no significant differences observed on the secondary outcomes. CONCLUSION This is the first effectiveness study to examine FACT in any population. The results suggest that it is effective compared with control, at one week, for patients with depressive symptoms in primary care.
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Affiliation(s)
- B Arroll
- Department of General Practice and Primary Healthcare, University of Auckland, Auckland, New Zealand
| | - H Frischtak
- Department of General Practice and Primary Healthcare, University of Auckland, Auckland, New Zealand
| | - R Roskvist
- Department of General Practice and Primary Healthcare, University of Auckland, Auckland, New Zealand
| | - V Mount
- Department of General Practice and Primary Healthcare, University of Auckland, Auckland, New Zealand
| | - F Sundram
- Department of Psychological Medicine, University of Auckland, Auckland, New Zealand
| | - S Fletcher
- Department of General Practice, The University of Melbourne, Melbourne, Australia
| | - D W Kingsford
- Interior Health Authority, Kelowna, British Columbia, Canada
| | - L Buttrick
- Department of General Practice and Primary Healthcare, University of Auckland, Auckland, New Zealand
| | - J Bricker
- Fred Hutchinson Center, Seattle, WA, USA
| | - B van der Werf
- Department of Epidemiology and Biostatistics, Faculty of Medical and Health Sciences, School of Population Health, University of Auckland, Auckland, New Zealand
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Ch S, Sudha S, Reddy CG, T P, KSBS KS, Dasari P, Battula P, T N, A S. A Comparative Study on Safety and Efficacy of Desvenlafaxine Versus Sertraline in Depression. Cureus 2022; 14:e22717. [PMID: 35371643 PMCID: PMC8971119 DOI: 10.7759/cureus.22717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/28/2022] [Indexed: 11/10/2022] Open
Abstract
Background Depression is one of the most predominant mental health issues that are prevalent now. Therefore, many clinical trials were being conducted to find the safest, most effective, and tolerable anti-depressant. This study aims to compare desvenlafaxine and sertraline regarding their safety and efficacy in treating depression. Methodology The patients who were diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria were included in the study and were divided into two groups. The severity of depression in these patients was evaluated using Beck Depression Inventory and Hamilton depression scale (HAM-D) before and after the treatment (four weeks). Results About 64% of the study sample were males, and 36% were females, with 77% of the patients in the desvenlafaxine group taking 100 mg dosage and about 74% patients taking 50 mg dosage in the sertraline group. The patients in both groups showed statistically significant (p < 0.00001) improvement after using these drugs. Conclusion Both desvenlafaxine and sertraline showed their efficacy in treating depression by improving the clinical outcome in patients. Sertraline was marginally better in clinical results. Finally, it is advisable to carry out more randomized trials to improve the patient’s quality of life.
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Carhart-Harris RL, Wagner AC, Agrawal M, Kettner H, Rosenbaum JF, Gazzaley A, Nutt DJ, Erritzoe D. Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine? J Psychopharmacol 2022; 36:6-11. [PMID: 33888025 PMCID: PMC8801625 DOI: 10.1177/02698811211008567] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Favourable regulatory assessments, liberal policy changes, new research centres and substantial commercial investment signal that psychedelic therapy is making a major comeback. Positive findings from modern trials are catalysing developments, but it is questionable whether current confirmatory trials are sufficient for advancing our understanding of safety and best practice. Here we suggest supplementing traditional confirmatory trials with pragmatic trials, real-world data initiatives and digital health solutions to better support the discovery of optimal and personalised treatment protocols and parameters. These recommendations are intended to help support the development of safe, effective and cost-efficient psychedelic therapy, which, given its history, is vulnerable to excesses of hype and regulation.
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Affiliation(s)
- Robin L Carhart-Harris
- Centre for Psychedelic Research, Imperial College London, London, UK,Robin L Carhart-Harris, Centre for Psychedelic Research, Imperial College London, Burlington Danes Building, London W12 0NN, UK.
| | - Anne C Wagner
- Remedy, Toronto, Canada,Department of Psychology, Ryerson University, Toronto, Canada
| | - Manish Agrawal
- Maryland Oncology and Hematology, Rockville, USA,Aquilino Cancer Center, Rockville, USA
| | - Hannes Kettner
- Centre for Psychedelic Research, Imperial College London, London, UK
| | | | - Adam Gazzaley
- Neuroscape, Department of Neurology, Physiology and Psychiatry, University of California San Francisco, San Francisco, USA
| | - David J Nutt
- Centre for Psychedelic Research, Imperial College London, London, UK
| | - David Erritzoe
- Centre for Psychedelic Research, Imperial College London, London, UK
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36
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Hengartner MP, Neuner-Jehle S, Senn O. Swiss GPs' preferences for antidepressant treatment in mild depression: vignette-based quantitative analysis. BMC FAMILY PRACTICE 2021; 22:261. [PMID: 34969372 PMCID: PMC8717647 DOI: 10.1186/s12875-021-01621-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/21/2021] [Indexed: 01/04/2023]
Abstract
Background GPs frequently prescribe antidepressants in mild depression. The aim of this study was to examine, how often Swiss GPs recommend antidepressants in various clinical presentations of mild depression and which factors contribute to antidepressant treatment recommendations. Methods We conducted an online survey among Swiss GPs with within-subject effect analysis. Alternating case vignettes described a typical female case of mild depression according to International Classification of Diseases, 10th edition criteria, with and without anxiety symptoms and sleep problems. GPs indicated for each vignette their preferred treatments (several recommendations were possible). Additionally, we assessed GP characteristics, attitudes towards depression treatments, and elements of clinical decision-making. Results Altogether 178 GPs completed the survey. In the initial description of a case with mild depression, 11% (95%-CI: 7%-17%) of GPs recommended antidepressants. If anxiety symptoms were added to the same case, 29% (23%-36%) recommended antidepressants. If sleep problems were mentioned, 47% (40%-55%) recommended antidepressants, and if both sleep problems and anxiety symptoms were mentioned, 63% (56%-70%) recommended antidepressants. Several factors were independently associated with increased odds of recommending antidepressants, specifically more years of practical experience, an advanced training in psychosomatic and psychosocial medicine, self-dispensation, and a higher perceived effectiveness of antidepressants. By contrast, a higher perceived influence of patient characteristics and the use of clinical practice guidelines were associated with reduced odds of recommending antidepressants. Conclusions Consistent with depression practice guidelines, Swiss GPs rarely recommended antidepressants in mild depression if no co-indications (i.e., sleep problems and anxiety symptoms) were depicted. However, presence of sleep problems and anxiety symptoms, many years of practical experience, overestimation of antidepressants’ effectiveness, self-dispensation, an advanced training in psychosomatic and psychosocial medicine, and non-use of clinical practice guidelines may independently lead to antidepressant over-prescribing. Supplementary Information The online version contains supplementary material available at 10.1186/s12875-021-01621-7.
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Affiliation(s)
- Michael P Hengartner
- Department of Applied Psychology, Zurich University of Applied Sciences (ZHAW), PO Box 707, CH-8037, Zurich, Switzerland.
| | - Stefan Neuner-Jehle
- Institute of Primary Care, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Oliver Senn
- Institute of Primary Care, University of Zurich and University Hospital Zurich, Zurich, Switzerland
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Duffy L, Clarke CS, Lewis G, Marston L, Freemantle N, Gilbody S, Hunter R, Kendrick T, Kessler D, King M, Lanham P, Mangin D, Moore M, Nazareth I, Wiles N, Bacon F, Bird M, Brabyn S, Burns A, Donkor Y, Hunt A, Pervin J, Lewis G. Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess 2021; 25:1-62. [PMID: 34842135 DOI: 10.3310/hta25690] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND There has been a steady increase in the number of primary care patients receiving long-term maintenance antidepressant treatment, despite limited evidence of a benefit of this treatment beyond 8 months. OBJECTIVE The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial investigated the clinical effectiveness and cost-effectiveness of antidepressant medication in preventing relapse in UK primary care. DESIGN This was a Phase IV, double-blind, pragmatic, multisite, individually randomised parallel-group controlled trial, with follow-up at 6, 12, 26, 39 and 52 weeks. Participants were randomised using minimisation on centre, type of antidepressant and baseline depressive symptom score above or below the median using Clinical Interview Schedule - Revised (two categories). Statisticians were blind to allocation for the outcome analyses. SETTING General practices in London, Bristol, Southampton and York. PARTICIPANTS Individuals aged 18-74 years who had experienced at least two episodes of depression and had been taking antidepressants for ≥ 9 months but felt well enough to consider stopping their medication. Those who met an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of depression or with other psychiatric conditions were excluded. INTERVENTION At baseline, participants were taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg. They were randomised to either remain on their current medication or discontinue medication after a tapering period. MAIN OUTCOME MEASURES The primary outcome was the time, in weeks, to the beginning of the first depressive episode after randomisation. This was measured by a retrospective Clinical Interview Schedule - Revised that assessed the onset of a depressive episode in the previous 12 weeks, and was conducted at 12, 26, 39 and 52 weeks. The depression-related resource use was collected over 12 months from medical records and patient-completed questionnaires. Quality-adjusted life-years were calculated using the EuroQol-5 Dimensions, five-level version. RESULTS Between 9 March 2017 and 1 March 2019, we randomised 238 participants to antidepressant continuation (the maintenance group) and 240 participants to antidepressant discontinuation (the discontinuation group). The time to relapse of depression was shorter in the discontinuation group, with a hazard ratio of 2.06 (95% confidence interval 1.56 to 2.70; p < 0.0001). By 52 weeks, relapse was experienced by 39% of those who continued antidepressants and 56% of those who discontinued antidepressants. The secondary analysis revealed that people who discontinued experienced more withdrawal symptoms than those who remained on medication, with the largest difference at 12 weeks. In the discontinuation group, 37% (95% confidence interval 28% to 45%) of participants remained on their randomised medication until the end of the trial. In total, 39% (95% confidence interval 32% to 45%) of participants in the discontinuation group returned to their original antidepressant compared with 20% (95% confidence interval 15% to 25%) of participants in maintenance group. The health economic evaluation demonstrated that participants randomised to discontinuation had worse utility scores at 3 months (-0.037, 95% confidence interval -0.059 to -0.015) and fewer quality-adjusted life-years over 12 months (-0.019, 95% confidence interval -0.035 to -0.003) than those randomised to continuation. The discontinuation pathway, besides giving worse outcomes, also cost more [extra £2.71 per patient over 12 months (95% confidence interval -£36.10 to £37.07)] than the continuation pathway, although the cost difference was not significant. CONCLUSIONS Patients who discontinue long-term maintenance antidepressants in primary care are at increased risk of relapse and withdrawal symptoms. However, a substantial proportion of patients can discontinue antidepressants without relapse. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants and improve shared decision-making. The participants may not have been representative of all people on long-term maintenance treatment and we could study only a restricted range of antidepressants and doses. Identifying patients who will not relapse if they discontinued antidepressants would be clinically important. TRIAL REGISTRATION Current Controlled Trials ISRCTN15969819 and EudraCT 2015-004210-26. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 69. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Larisa Duffy
- Division of Psychiatry, University College London, London, UK
| | - Caroline S Clarke
- Research Department of Primary Care and Population Health, University College London, London, UK.,PRIMENT Clinical Trials Unit, University College London, London, UK
| | - Gemma Lewis
- Division of Psychiatry, University College London, London, UK
| | - Louise Marston
- Research Department of Primary Care and Population Health, University College London, London, UK.,PRIMENT Clinical Trials Unit, University College London, London, UK
| | - Nick Freemantle
- PRIMENT Clinical Trials Unit, University College London, London, UK.,Comprehensive Clinical Trials Unit, University College London, London, UK
| | - Simon Gilbody
- Department of Health and Social Care Sciences, University of York, York, UK
| | - Rachael Hunter
- Research Department of Primary Care and Population Health, University College London, London, UK.,PRIMENT Clinical Trials Unit, University College London, London, UK
| | - Tony Kendrick
- Primary Care Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - David Kessler
- Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Michael King
- Research Department of Primary Care and Population Health, University College London, London, UK.,PRIMENT Clinical Trials Unit, University College London, London, UK
| | - Paul Lanham
- Division of Psychiatry, University College London, London, UK
| | - Dee Mangin
- Department of Family Medicine, McMaster University, Hamilton, ON, Canada.,Department of General Practice, University of Otago, Christchurch, New Zealand
| | - Michael Moore
- Primary Care Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - Irwin Nazareth
- Research Department of Primary Care and Population Health, University College London, London, UK.,PRIMENT Clinical Trials Unit, University College London, London, UK
| | - Nicola Wiles
- Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Faye Bacon
- Division of Psychiatry, University College London, London, UK
| | - Molly Bird
- Division of Psychiatry, University College London, London, UK
| | - Sally Brabyn
- Department of Health and Social Care Sciences, University of York, York, UK
| | - Alison Burns
- Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Yvonne Donkor
- Division of Psychiatry, University College London, London, UK
| | - Anna Hunt
- Primary Care Population Sciences and Medical Education, University of Southampton, Southampton, UK
| | - Jodi Pervin
- Department of Health and Social Care Sciences, University of York, York, UK
| | - Glyn Lewis
- Division of Psychiatry, University College London, London, UK
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Lewis G, Marston L, Duffy L, Freemantle N, Gilbody S, Hunter R, Kendrick T, Kessler D, Mangin D, King M, Lanham P, Moore M, Nazareth I, Wiles N, Bacon F, Bird M, Brabyn S, Burns A, Clarke CS, Hunt A, Pervin J, Lewis G. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med 2021; 385:1257-1267. [PMID: 34587384 DOI: 10.1056/nejmoa2106356] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting. METHODS We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings. RESULTS A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group. CONCLUSIONS Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.).
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Affiliation(s)
- Gemma Lewis
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Louise Marston
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Larisa Duffy
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Nick Freemantle
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Simon Gilbody
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Rachael Hunter
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Tony Kendrick
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - David Kessler
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Dee Mangin
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Michael King
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Paul Lanham
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Michael Moore
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Irwin Nazareth
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Nicola Wiles
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Faye Bacon
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Molly Bird
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Sally Brabyn
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Alison Burns
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Caroline S Clarke
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Anna Hunt
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Jodi Pervin
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
| | - Glyn Lewis
- From the Division of Psychiatry, Faculty of Brain Sciences (Gemma Lewis, L.D., M.K., P.L., F.B., M.B., Glyn Lewis), the Research Department of Primary Care and Population Health and Priment Clinical Trials Unit (L.M., R.H., I.N., C.S.C.), and the Institute of Clinical Trials and Methodology (N.F.), University College London, London, the Department of Health Sciences and Hull York Medical School, University of York, York (S.G., S.B., J.P.), Primary Care Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton (T.K., M.M., A.H.), and Population Health Sciences (D.K.) and the Centre for Academic Mental Health (N.W., A.B.), Bristol Medical School, University of Bristol, Bristol - all in the United Kingdom; and the Department of Family Medicine, McMaster University, Hamilton, ON, Canada (D.M.)
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Rajyaguru P, Kwong ASF, Braithwaite E, Pearson RM. Maternal and paternal depression and child mental health trajectories: evidence from the Avon Longitudinal Study of Parents and Children. BJPsych Open 2021; 7:e166. [PMID: 34556196 PMCID: PMC8485341 DOI: 10.1192/bjo.2021.959] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The relationships between offspring depression profiles across adolescence and different timings of parental depression during the perinatal period remain unknown. AIMS To explore different timings of maternal and paternal perinatal depression in relation to patterns of change in offspring depressive mood over a 14 year period. METHOD Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental antenatal depression (ANTD) was assessed at 18 weeks gestation, and postnatal depression (PNTD) at 8 weeks postpartum. Population-averaged trajectories of offspring depressive symptoms were estimated using the Short Mood and Feelings Questionnaire (SMFQ) on nine occasions between 10 and 24 years of age. RESULTS Full data were available for 5029 individuals. Offspring exposed to both timings of maternal depression had higher depressive symptoms across adolescence compared with offspring not exposed to ANTD or PNTD, characterised by higher depressive symptoms at age 16 (7.07 SMFQ points (95% CI = 6.19, 7.95; P < 0.001)) and a greater rate of linear change (0.698 SMFQ points (95% CI = 0.47, 0.93; P = 0.002)). Isolated maternal ANTD and to a lesser extent PNTD were also both associated with higher depressive symptoms at age 16, yet isolated maternal PNTD showed greater evidence for an increased rate of linear change across adolescence. A similar pattern was observed for paternal ANTD and PNTD, although effect sizes were attenuated. CONCLUSIONS This study adds to the literature demonstrating that exposure to two timings of maternal depression (ANTD and PNTD) is strongly associated with greater offspring trajectories of depressive symptoms.
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Affiliation(s)
- Priya Rajyaguru
- Centre for Academic Mental Health, University of Bristol, Bristol, and Oxford Health NHS Foundation Trust, UK
| | - Alex S F Kwong
- Population Health Sciences, Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK
| | - Elizabeth Braithwaite
- Department of Psychology, School of Health, Psychology and Social Care, Manchester Metropolitan University, Manchester, UK
| | - Rebecca M Pearson
- Population Health Sciences, Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit, University of Bristol, and National Institute for Health Research Bristol Biomedical Research Centre, Bristol, UK
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Spence O, Reeves G, dosReis S. Evaluating the association between antidepressant dose trajectories and treatment augmentation in pediatric depression. Pharmacoepidemiol Drug Saf 2021; 31:176-186. [PMID: 34529312 DOI: 10.1002/pds.5358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 09/08/2021] [Accepted: 09/13/2021] [Indexed: 11/08/2022]
Abstract
PURPOSE To identify antidepressant dose trajectories in the first 6-months of antidepressant initiation and to evaluate the association between antidepressant dose trajectories and augmentation with another psychotropic medication. METHODS Using the IQVIA PharMetrics® Plus database, we identified 5655 commercially insured youth (3-18 years) with depression who newly initiated an antidepressant anytime from January 2007 to June 2015. No antidepressant use within 1 year prior to the index prescription defined new use. Latent class growth analysis of antidepressant dosing in the 6 months after initiation defined the exposure groups. The outcome was any regimen change, that is, antidepressant augmentation with another psychotropic or discontinuation of the antidepressant, with and without switching to another psychotropic. Baseline covariates measured in the 6 months before antidepressant initiation included demographic factors, psychiatric comorbidities, and health service use. Multinomial logistic regression tested the association between antidepressant dose trajectories and the odds of an antidepressant regimen change. RESULTS Five dose trajectories were sharp decline (n = 897; 16%), slow decline (n = 1029; 18%), stable minimum dose (n = 1397; 25%), stable maximum dose (n = 1783; 32%), and increasing high dose (n = 549; 10%). Relative to the stable minimum dose group, the sharp and slow decline groups were more likely to discontinue the antidepressant, either switch to another psychotropic (OR [odds ratio]: 5.91; 95%CI: 3.23-10.80 and OR: 1.67; 95%CI: 1.04-2.68, respectively) or stop all psychotropic medication (OR: 6.64; 95%CI: 4.24-10.39 and OR: 1.62; 95%CI: 1.22-2.13, respectively). However, the stable maximum and increasing high-dose groups were less likely to discontinue, either switch (OR: 0.38; 95%CI: 0.24-0.61 and OR: 0.30; 95%CI: 0.16-0.59, respectively) or stop all psychotropic medications (OR: 0.15; 95%CI: 0.12-0.20 and OR: 0.02; 95%CI: 0.01-0.03 respectively) than augment with another psychotropic. CONCLUSIONS The findings from this cross-sectional study demonstrate an association between antidepressant dose trajectories within 6 months of initiating treatment and the odds of augmenting with another psychotropic.
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Affiliation(s)
- O'Mareen Spence
- Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
| | - Gloria Reeves
- Division of Child and Adolescent Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Susan dosReis
- Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
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Revisiting Treatment Options for Depressed Patients with Generalised Anxiety Disorder. Adv Ther 2021; 38:61-68. [PMID: 34417993 PMCID: PMC8437852 DOI: 10.1007/s12325-021-01861-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 07/12/2021] [Indexed: 12/20/2022]
Abstract
Symptoms of anxiety and depression often coexist, and evidence suggests that this has a genetic basis, among other possible causes. However, the current classification of comorbid generalised anxiety disorder (GAD) and depression (anxious depression) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition; DSM-5) does not fully reflect the high prevalence of anxiety symptoms in people with depression and the International Classification of Diseases (10th and 11th revisions) has tended to identify anxious depression with minor disorders seen in primary care. As a result, few dedicated therapeutic trials have been conducted in patients with anxious depression, and specific treatment guidelines and recommendations are lacking. Fortunately, there is considerable therapeutic overlap between anxiety and depression, such that many agents with antidepressant efficacy are also effective for symptoms of GAD. The initial treatment of a patient with depression and symptoms of anxiety should be with an agent that is approved for both major depressive disorder and GAD, such as a selective serotonin reuptake inhibitor. There is an obvious need for greater recognition of anxious depression in order to boost the volume of high-quality clinical data, which should translate over time into better, more specific treatment recommendations and improved outcomes.
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Van Tiem J, Moeckli J, Suiter N, Fuhrmeister L, Pham K, Dindo L, Turvey C. "A link to the outside:" Patient perspectives on a mobile texting program to improve depression self-management. PATIENT EDUCATION AND COUNSELING 2021; 104:2154-2158. [PMID: 33627234 DOI: 10.1016/j.pec.2021.02.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/16/2020] [Accepted: 02/09/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND The effectiveness of technology-assisted interventions designed to ameliorate depressive symptoms and improve antidepressant medication adherence is hampered by diminished usage over time and poor integration with clinical care. OBJECTIVE This manuscript presents patient perspectives on a texting and secure messaging intervention designed to engage providers and patients during a targeted transition period when patients were initiating a new antidepressant medication. PATIENT INVOLVEMENT Development of the intervention was guided by feedback from a presentation and discussion with an engagement panel of local stakeholders, including patients, who meet quarterly with research investigators. METHODS Semi-structured, qualitative, telephone interviews were conducted with 21 participants. Interviews were designed to identify the themes of self-determination and planned behavior in using the text messaging intervention. Qualitative analysis of participants' experiences used inductive and deductive coding, as well as pile sorting. RESULTS The intervention prompted participants to reflect about how they manage their mood, engage in behaviors guided by their values, and commit to making positive changes in how they acted in real-time. Elements of the intervention facilitated participant conversations with trusted friends and family over time about what had influenced their actions and feelings. DISCUSSION The texting intervention appeared to help participants live a life consistent with their values. However, we were unable to recruit mental health providers to participate. PRACTICAL VALUE Technology to promote self-reflection and an "observing self" may work best when done in dialogue with important others, including mental health providers. Future directions of this research should find ways to understand provider buy-in, or lack thereof, in e-health interventions.
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Affiliation(s)
- Jen Van Tiem
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System (152), Iowa City, IA, USA; Iowa City Rural Health Resource Center, Iowa City VA Health Care System (152), Iowa City, IA, USA.
| | - Jane Moeckli
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System (152), Iowa City, IA, USA; Iowa City Rural Health Resource Center, Iowa City VA Health Care System (152), Iowa City, IA, USA.
| | - Natalie Suiter
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System (152), Iowa City, IA, USA; Iowa City Rural Health Resource Center, Iowa City VA Health Care System (152), Iowa City, IA, USA.
| | - Lindsey Fuhrmeister
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System (152), Iowa City, IA, USA; Iowa City Rural Health Resource Center, Iowa City VA Health Care System (152), Iowa City, IA, USA.
| | - Kassi Pham
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System (152), Iowa City, IA, USA; Iowa City Rural Health Resource Center, Iowa City VA Health Care System (152), Iowa City, IA, USA.
| | - Lilian Dindo
- Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, TX, USA; Houston Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
| | - Carolyn Turvey
- Center for Access and Delivery Research and Evaluation (CADRE), Iowa City VA Health Care System (152), Iowa City, IA, USA; Iowa City Rural Health Resource Center, Iowa City VA Health Care System (152), Iowa City, IA, USA; Department of Psychiatry, Carver College of Medicine, University of Iowa, 451 Newton Road, 200 Medicine Administration Building, Iowa City, IA, USA.
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Edinoff AN, Fort JM, Woo JJ, Causey CD, Burroughs CR, Cornett EM, Kaye AM, Kaye AD. Selective Serotonin Reuptake Inhibitors and Clozapine: Clinically Relevant Interactions and Considerations. Neurol Int 2021; 13:445-463. [PMID: 34564289 PMCID: PMC8482107 DOI: 10.3390/neurolint13030044] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 07/29/2021] [Accepted: 08/12/2021] [Indexed: 12/21/2022] Open
Abstract
The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.
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Affiliation(s)
- Amber N Edinoff
- Department of Psychiatry and Behavioral Medicine, Louisiana State University Health Science Center Shreveport, 1501 Kings Hwy, Shreveport, LA 71103, USA
| | - Juliana M Fort
- Department of Psychiatry and Behavioral Medicine, Louisiana State University Health Science Center Shreveport, 1501 Kings Hwy, Shreveport, LA 71103, USA
| | - Joshua J Woo
- School of Medicine, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA
| | - Christopher D Causey
- School of Medicine, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA
| | - Caroline R Burroughs
- School of Medicine, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA
| | - Elyse M Cornett
- Department of Anesthesiology, Louisiana State University Health Science Center Shreveport, Shreveport, LA 71103, USA
| | - Adam M Kaye
- Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA
| | - Alan D Kaye
- Department of Anesthesiology, Louisiana State University Health Science Center Shreveport, Shreveport, LA 71103, USA
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Bauer-Staeb C, Kounali DZ, Welton NJ, Griffith E, Wiles NJ, Lewis G, Faraway JJ, Button KS. Effective dose 50 method as the minimal clinically important difference: Evidence from depression trials. J Clin Epidemiol 2021; 137:200-208. [PMID: 33892086 PMCID: PMC8485844 DOI: 10.1016/j.jclinepi.2021.04.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 03/24/2021] [Accepted: 04/13/2021] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity. STUDY DESIGN AND SETTINGS The present analysis used secondary data from 2 randomized controlled trials for depression (n = 1,122) to calibrate the Global Rating of Change with the PHQ-9 and GAD-7. The MCID was defined as a change in scores corresponding to a 50% probability of patients "feeling better", given their baseline severity, referred to as Effective Dose 50 (ED50). RESULTS MCID estimates depended on baseline severity and ranged from no change for very mild up to 14 points (52%) on the PHQ-9 and up to 10 points (48%) on the GAD-7 for very high severity. The average MCID estimates were 3.7 points (23%) and 3.3 (28%) for the PHQ-9 and GAD-7 respectively. CONCLUSION The ED50 method generates MCID estimates across the spectrum of baseline severity, offering greater precision but at the cost of greater complexity relative to population average estimates. This has important implications for evaluations of treatments and clinical practice where users can use these results to tailor the MCID to specific populations according to baseline severities.
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Affiliation(s)
| | | | - Nicky J Welton
- Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Emma Griffith
- Department of Psychology, University of Bath, Bath, United Kingdom; Avon and Wiltshire Mental Health Partnership NHS Trust, Bath, United Kingdom
| | - Nicola J Wiles
- Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Glyn Lewis
- Division of Psychiatry, University College London, London, United Kingdom
| | - Julian J Faraway
- Department of Mathematical Sciences, University of Bath, Bath, United Kingdom
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Zazula R, Husain MI, Mohebbi M, Walker AJ, Chaudhry IB, Khoso AB, Ashton MM, Agustini B, Husain N, Deakin J, Young AH, Berk M, Kanchanatawan B, Ng CH, Maes M, Berk L, Singh AB, Malhi GS, Dean OM. Minocycline as adjunctive treatment for major depressive disorder: Pooled data from two randomized controlled trials. Aust N Z J Psychiatry 2021; 55:784-798. [PMID: 33092404 DOI: 10.1177/0004867420965697] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. METHODS Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery-Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery-Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. RESULTS A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms - differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen's D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 - anxiety severity - differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen's D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status - differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen's D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. CONCLUSION The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. TRIAL REGISTRATIONS NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.
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Affiliation(s)
- Robson Zazula
- Latin American Institute for the Science of Life and Nature, Federal University of Latin American Integration, Foz do Iguacu, Brazil.,Health Sciences Graduate Program, Londrina State University, Londrina, Brazil.,Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia
| | - Muhammad Ishrat Husain
- Department of Psychiatry, University of Toronto, Toronto, Canada.,Centre for Addiction and Mental Health, Toronto, Canada
| | - Mohammadreza Mohebbi
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia.,Deakin University, Faculty of Health, Biostatistics Unit, Geelong, Australia
| | - Adam J Walker
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia
| | - Imran B Chaudhry
- Department of Psychiatry, Ziauddin University, Karachi, Pakistan.,Pakistan Institute of Living and Learning, Karachi, Pakistan.,University of Manchester, Manchester, UK
| | - Ameer B Khoso
- Pakistan Institute of Living and Learning, Karachi, Pakistan
| | - Melanie M Ashton
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia
| | - Bruno Agustini
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia
| | | | - Jfw Deakin
- University of Manchester, Manchester, UK
| | - Allan H Young
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.,South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent, UK
| | - Michael Berk
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia.,Florey Institute for Neuroscience and Mental Health, University of Melbourne, Australia.,The Melbourne Clinic, Department of Psychiatry, University of Melbourne, Australia.,Orygen the National Centre of Excellence in Youth Mental Health, Parkville, Australia
| | | | - Chee H Ng
- The Melbourne Clinic, Department of Psychiatry, University of Melbourne, Australia
| | - Michael Maes
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia.,Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand
| | - Lesley Berk
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia.,Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
| | - Ajeet B Singh
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia
| | - Gin S Malhi
- The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, New South Wales, Australia.,Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Australia.,CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, Australia
| | - Olivia M Dean
- Deakin University, iMPACT, the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, Australia.,Florey Institute for Neuroscience and Mental Health, University of Melbourne, Australia
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Gougoulaki M, Lewis G, Nutt DJ, Peters TJ, Wiles NJ, Lewis G. Sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitor antidepressants: Secondary analyses of the GENPOD trial. J Psychopharmacol 2021; 35:919-927. [PMID: 33637001 PMCID: PMC8358567 DOI: 10.1177/0269881120986417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Differences in serotonergic neurotransmission could lead to sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitors (SSRIs). AIMS We investigated whether women have greater reductions in depressive symptoms than men after treatment with an SSRI (citalopram) compared with a noradrenaline reuptake inhibitor (reboxetine) control, and after antidepressant treatment irrespective of class. We also investigated tolerability and the influence of menopausal status. METHODS Secondary analyses of the GENPOD (GENetic and clinical Predictors Of treatment response in Depression) trial. Six hundred and one people with depression were recruited from UK primary care and randomized to citalopram or reboxetine. Beck Depression Inventory (BDI-II) score at 6 weeks was the primary outcome. Secondary outcomes included BDI-II score at 12 weeks, and physical symptoms and treatment discontinuation. We calculated main effects and interaction terms using linear and logistic regression models. RESULTS There was no evidence that women experienced greater reductions in depressive symptoms than men when treated with citalopram compared with reboxetine. We also found no evidence of sex differences at six or 12 weeks (irrespective of antidepressant class): men scored -0.31 (95% confidence interval (CI) -2.23 to 1.62) BDI-II points lower than women at six weeks and -0.44 (95% CI -2.62 to 1.74) points lower at 12 weeks. There was no evidence of sex differences in physical symptoms or treatment discontinuation and no evidence for an influence of menopausal status. CONCLUSION Citalopram was not more effective in women compared with men and there was no difference in tolerability. Women and men had similar prognosis after SSRI treatment and similar prognosis regardless of antidepressant class. Findings were unaltered by menopausal status.
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Affiliation(s)
| | - Glyn Lewis
- Division of Psychiatry, Faculty of Brain Sciences, University College London, London, UK
| | - David J Nutt
- Department of Psychiatry, Division of Brain Science, Imperial College, London, UK
| | - Tim J Peters
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Nicola J Wiles
- Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Gemma Lewis
- Division of Psychiatry, Faculty of Brain Sciences, University College London, London, UK,Gemma Lewis, Division of Psychiatry, UCL, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UK.
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Buckman JEJ, Saunders R, Stott J, Arundell LL, O'Driscoll C, Davies MR, Eley TC, Hollon SD, Kendrick T, Ambler G, Cohen ZD, Watkins E, Gilbody S, Wiles N, Kessler D, Richards D, Brabyn S, Littlewood E, DeRubeis RJ, Lewis G, Pilling S. Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis. Epidemiol Psychiatr Sci 2021; 30:e42. [PMID: 34085616 PMCID: PMC7610920 DOI: 10.1017/s2045796021000342] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/04/2021] [Accepted: 05/09/2021] [Indexed: 11/21/2022] Open
Abstract
AIMS To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.
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Affiliation(s)
- J. E. J. Buckman
- Research Department of Clinical, Educational & Health Psychology, Centre for Outcomes Research and Effectiveness (CORE), University College London, 1-19 Torrington Place, LondonWC1E 7HB, UK
- iCope – Camden & Islington NHS Foundation Trust, St Pancras Hospital, LondonNW1 0PE, UK
| | - R. Saunders
- Research Department of Clinical, Educational & Health Psychology, Centre for Outcomes Research and Effectiveness (CORE), University College London, 1-19 Torrington Place, LondonWC1E 7HB, UK
| | - J. Stott
- Research Department of Clinical, Educational & Health Psychology, Centre for Outcomes Research and Effectiveness (CORE), University College London, 1-19 Torrington Place, LondonWC1E 7HB, UK
| | - L.-L. Arundell
- Research Department of Clinical, Educational & Health Psychology, Centre for Outcomes Research and Effectiveness (CORE), University College London, 1-19 Torrington Place, LondonWC1E 7HB, UK
| | - C. O'Driscoll
- Research Department of Clinical, Educational & Health Psychology, Centre for Outcomes Research and Effectiveness (CORE), University College London, 1-19 Torrington Place, LondonWC1E 7HB, UK
| | - M. R. Davies
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, LondonSE5 8AF, UK
| | - T. C. Eley
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, LondonSE5 8AF, UK
| | - S. D. Hollon
- Department of Psychology, Vanderbilt University, Nashville, TN37240, USA
| | - T. Kendrick
- Faculty of Medicine, Primary Care, Population Sciences and Medical Education, University of Southampton, SouthamptonSO16 5ST, UK
| | - G. Ambler
- Statistical Science, University College London, LondonWC1E 7HB, UK
| | - Z. D. Cohen
- Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - E. Watkins
- Department of Psychology, University of Exeter, ExeterEX4 4QG, UK
| | - S. Gilbody
- Department of Health Sciences, University of York, YorkYO10 5DD, UK
| | - N. Wiles
- Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, BristolBS8 2BN, UK
| | - D. Kessler
- Centre for Academic Primary Care, Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, Bristol, UK
| | - D. Richards
- Institute of Health Research, University of Exeter College of Medicine and Health, ExeterEX1 2LU, UK
- Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Inndalsveien 28, 5063Bergen, Norway
| | - S. Brabyn
- Department of Health Sciences, University of York, YorkYO10 5DD, UK
| | - E. Littlewood
- Department of Health Sciences, University of York, YorkYO10 5DD, UK
| | - R. J. DeRubeis
- Department of Psychology, School of Arts and Sciences, 425 S. University Avenue, PhiladelphiaPA, 19104-60185, USA
| | - G. Lewis
- Division of Psychiatry, University College London, LondonW1T 7NF, UK
| | - S. Pilling
- Research Department of Clinical, Educational & Health Psychology, Centre for Outcomes Research and Effectiveness (CORE), University College London, 1-19 Torrington Place, LondonWC1E 7HB, UK
- Camden & Islington NHS Foundation Trust, 4 St Pancras Way, LondonNW1 0PE, UK
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48
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The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial. Neuropsychopharmacology 2021; 46:1307-1314. [PMID: 33637837 PMCID: PMC8134561 DOI: 10.1038/s41386-021-00981-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 11/25/2022]
Abstract
Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients.
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49
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Walker A, Naughton MT, Shaw L, Jeklin AT, Martin C, Dabscheck E. Depression scores improve with continuous positive airway pressure in specialized sleep clinics: real-world data. J Clin Sleep Med 2021; 17:1201-1209. [PMID: 33590822 DOI: 10.5664/jcsm.9164] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
STUDY OBJECTIVES To assess changes in Hospital Anxiety and Depression Scale (HADS) scores after continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea. METHODS Consecutive patients attending the Alfred Health sleep clinic, diagnosed with obstructive sleep apnea, and prescribed CPAP were recruited. The primary outcome was a change in the HADS depression (HADS-D) and anxiety (HADS-A) subscales from the time of diagnosis to follow-up. Secondary analysis compared high (> 4 hours) and low (< 4 hours) CPAP adherence groups and change in depression cases, defined by HADS-D ≥ 8, and anxiety cases, defined by HADS-A ≥ 11. RESULTS We included 108 participants in the final analysis. Adherence groups were well matched in baseline mood, sleepiness, and apnea variables. Overall age (mean ± standard deviation) was 56.1 ± 12.8 years, and there was a median (interquartile ratio) apnea-hypopnea-index of 42.7 (27.5-58.1) or median (interquartile ratio) oxygen-desaturation-index of 43.0 (26.0-74.0). The median duration of CPAP therapy was 1.3 years. The HADS-D decreased after CPAP by -1.4 (adjusted 95% confidence interval, -2.1 to -0.6; P = .001). Patients with high-CPAP adherence (n = 84) had a tendency towards a greater reduction in HADS-D (-1.5) compared with those with low-CPAP adherence (n = 24; -0.3; adjusted P = .19). Depression cases (HADS-D ≥ 8) decreased by 13.1% in the high-CPAP-adherence group (P = .03) and increased by 4.1% in the low-CPAP-adherence group (P = .71). The HADS-A decreased after CPAP by -1.8 (adjusted 95% confidence interval, -1.8 to -0.4; P = .004). There was no significant difference between adherence groups or anxiety cases (HADS-A > 11). CONCLUSIONS Specialized obstructive sleep apnea treatment with CPAP reduces depression scores, with a trend toward greater reduction in those with high CPAP adherence.
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Affiliation(s)
- Anne Walker
- Department of Thoracic Medicine, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia.,University of Adelaide, Adelaide, Australia
| | - Matthew T Naughton
- Department of Respiratory Medicine, Alfred Health, Melbourne, Australia.,School of Medicine, Monash University, Victoria, Melbourne, Australia
| | - Lachlan Shaw
- School of Medicine, Monash University, Victoria, Melbourne, Australia
| | - Andrew T Jeklin
- School of Medicine, Monash University, Victoria, Melbourne, Australia
| | - Catherine Martin
- Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
| | - Eli Dabscheck
- Department of Respiratory Medicine, Alfred Health, Melbourne, Australia.,School of Medicine, Monash University, Victoria, Melbourne, Australia
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50
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Kwong ASF, Pearson RM, Adams MJ, Northstone K, Tilling K, Smith D, Fawns-Ritchie C, Bould H, Warne N, Zammit S, Gunnell DJ, Moran PA, Micali N, Reichenberg A, Hickman M, Rai D, Haworth S, Campbell A, Altschul D, Flaig R, McIntosh AM, Lawlor DA, Porteous D, Timpson NJ. Mental health before and during the COVID-19 pandemic in two longitudinal UK population cohorts. Br J Psychiatry 2021; 218:334-343. [PMID: 33228822 PMCID: PMC7844173 DOI: 10.1192/bjp.2020.242] [Citation(s) in RCA: 305] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/10/2020] [Accepted: 11/10/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences. AIMS To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic. METHOD Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale. RESULTS Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23-26%) compared with a pre-pandemic level of 13% (95% CI 12-14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression. CONCLUSIONS These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.
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Affiliation(s)
- Alex S. F. Kwong
- MRC Integrative Epidemiology Unit, University of Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, UK; and Division of Psychiatry, University of Edinburgh, UK
| | - Rebecca M. Pearson
- MRC Integrative Epidemiology Unit, University of Bristol, UK; and Population Health Sciences, Bristol Medical School, University of Bristol, UK
| | | | - Kate Northstone
- Population Health Sciences, Bristol Medical School, University of Bristol, UK
| | - Kate Tilling
- MRC Integrative Epidemiology Unit, University of Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, UK; and Division of Psychiatry, University of Edinburgh, UK
| | - Daniel Smith
- MRC Integrative Epidemiology Unit, University of Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, UK; and Division of Psychiatry, University of Edinburgh, UK
| | | | - Helen Bould
- Population Health Sciences, Bristol Medical School, University of Bristol, UK; and Gloucestershire Health and Care NHS Foundation Trust, UK
| | - Naomi Warne
- Population Health Sciences, Bristol Medical School, University of Bristol, UK
| | - Stanley Zammit
- Population Health Sciences, Bristol Medical School, University of Bristol, UK; and MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK
| | - David J. Gunnell
- Population Health Sciences, Bristol Medical School, University of Bristol, UK; and National Institute of Health Research Biomedical Research Centre, University of Bristol, UK
| | - Paul A. Moran
- Population Health Sciences, Bristol Medical School, University of Bristol, UK; National Institute of Health Research Biomedical Research Centre, University of Bristol, UK; and Avon and Wiltshire Mental Health Partnership NHS Trust, UK
| | - Nadia Micali
- Great Ormond Street Institute of Child Health, University College London, UK; Department of Psychiatry, Faculty of Medicine, University of Geneva, Switzerland; and Department of Paediatrics Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva, Switzerland
| | - Abraham Reichenberg
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Matthew Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, UK
| | - Dheeraj Rai
- Population Health Sciences, Bristol Medical School, University of Bristol, UK; National Institute of Health Research Biomedical Research Centre, University of Bristol, UK; and Avon and Wiltshire Mental Health Partnership NHS Trust, UK
| | - Simon Haworth
- 1MRC Integrative Epidemiology Unit, University of Bristol, UK; and Population Health Sciences, Bristol Medical School, University of Bristol, UK
| | - Archie Campbell
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, UK; and Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, UK
| | - Drew Altschul
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, UK
| | - Robin Flaig
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, UK; and Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, UK
| | | | - Deborah A. Lawlor
- MRC Integrative Epidemiology Unit at the University of Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, UK; and National Institute of Health Research Biomedical Research Centre, University of Bristol, UK
| | - David Porteous
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, UK
| | - Nicholas J. Timpson
- MRC Integrative Epidemiology Unit at the University of Bristol, UK; and Population Health Sciences, Bristol Medical School, University of Bristol, UK
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