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Yıldız GN, Çiftçi B. Interplay between insomnia, anxiety, and depression. World J Psychiatry 2025; 15:104796. [DOI: 10.5498/wjp.v15.i6.104796] [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: 01/01/2025] [Revised: 03/11/2025] [Accepted: 04/07/2025] [Indexed: 05/29/2025] Open
Abstract
Insomnia, anxiety, and depression have become critical mental health issues exacerbated by the coronavirus disease 2019 pandemic, highlighting the importance of understanding their interrelationships. This article evaluates the study by Li et al, which investigates the links between insomnia, anxiety, and depression while examining the mediating role of cognitive failures and the moderating effect of neuroticism. The study employed a cross-sectional design with 1011 participants, using validated scales to measure insomnia severity, neuroticism, cognitive failures, and mental health indicators. Li et al found that approximately 40% of participants exhibited symptoms of anxiety, depression, and insomnia, with most cases being mild. The results demonstrated that cognitive failures play a mediating role in the relationship between insomnia and both anxiety and depression. Furthermore, neuroticism moderated the relationship between insomnia and cognitive failures, with a stronger effect observed in individuals with lower levels of neuroticism. These findings underscore the importance of considering personality traits and cognitive processes in understanding mental health outcomes. This study emphasizes the critical need for interventions aimed at reducing cognitive failures and enhancing emotional stability to mitigate the impact of insomnia on mental health. Strategies to improve sleep quality, boost cognitive resilience, and regulate emotional responses could significantly enhance individuals’ mental well-being. Moreover, integrating personality assessments into mental health services could facilitate more effective and personalized interventions. This article provides an original perspective on the effects of the coronavirus disease 2019 pandemic on global mental health. The content of the article addresses the complex relationships between sleep disorders, cognitive function losses, and neuroticism in light of data compiled from existing literature and current research. In addition, how these relationships have deepened during the pandemic and the effectiveness of proposed treatment methods for these phenomena are discussed in comparison with previous studies. The arguments in the article offer new perspectives and suggestions aimed at filling gaps in the literature, and make an important contribution to both clinical practice and public health policies. Li et al’s study provides a comprehensive framework for understanding the connections between insomnia, cognitive failures, and neuroticism, as well as their influence on anxiety and depression. The findings offer valuable implications for public health strategies, emphasizing the necessity of holistic approaches to address post-pandemic mental health challenges.
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Affiliation(s)
- Güzel Nur Yıldız
- Department of Dialysis, Muş Alparslan University, Muş 40199, Türkiye
| | - Bahar Çiftçi
- Department of Fundamental Nursing, Ataturk University, Erzurum 25240, Türkiye
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Sforza M, Morin CM, Dang-Vu TT, Pomares FB, Perrault AA, Gouin JP, Bušková J, Janků K, Vgontzas A, Fernandez-Mendoza J, Bastien CH, Riemann D, Baglioni C, Carollo G, Casoni F, Zucconi M, Castronovo V, Galbiati A, Ferini-Strambi L. Cognitive-behavioural therapy for insomnia mechanism of action: Exploring the homeostatic K-complex involvement. J Sleep Res 2024:e14452. [PMID: 39739397 DOI: 10.1111/jsr.14452] [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: 07/05/2024] [Revised: 11/13/2024] [Accepted: 12/11/2024] [Indexed: 01/02/2025]
Abstract
Investigating the mechanisms of action of cognitive-behavioural therapy for insomnia (CBT-I), the first-line treatment for chronic insomnia disorder (ID), can contribute to the overall understanding of insomnia and its treatment. To date, no study has examined the relationship between K-complexes (KC) and CBT-I, despite the known homeostatic and protective function of this relevant sleep brainwave. This retrospective multicentre study aims to explore the relationship between electroencephalographic (EEG) indices and CBT-I, with a particular focus on evaluating an index of sleep homeostasis identified by KC. This research is designed to assess the predictive value of this index for treatment outcomes and to examine its variations before and after intervention. Ninety eight patients with ID underwent a 6-8 week in-person CBT-I programme, with pre-and post-treatment evaluation conducted using polysomnography (PSG) and the Insomnia Severity Index (ISI). The main outcome was determined by calculating the slope of the linear equation indexing the KC density (number of KC/minutes of N2) in each non-artifacted NREM stage 2 epoch throughout the night (KCSlope). Furthermore, the sample was categorised into Responders (ISIdecrease ≥8) and non-Responders (ISIdecrease <8). The results indicate that the KC Slope is effective not only to predict treatment response (one-way ANOVA, F = 7.831 p = 0.007; Responders = -2.954*10-5 ± 3.346*10-5, non-Responders = -5.583*10-5 ± 5.305*10-5; adjusted for PSG wake after sleep onset at the baseline), but also to detect a statistically significant improvement in sleep pressure following CBT-I (Wilcoxon signed-rank test W = 3074.000 p = 0.022; KCSlope pre-treatment = -4.054*10-5 ± 4.446*10-5, KCSlope post-treatment = -4.797*10-5 ± 5.710*10-5). These findings suggest that CBT-I increases sleep pressure in patients with chronic insomnia, highlighting a novel and relevant biomarker in this context.
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Affiliation(s)
- Marco Sforza
- Vita-Salute San Raffaele University, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
| | - Charles M Morin
- School of Psychology and Centre de Recherche CERVO, Université Laval, Québec, Quebec, Canada
| | - Thien Thanh Dang-Vu
- School of Health, Concordia University, Centre de recherches de l'Institut universitaire de gériatrie de Montréal (CRIUGM), CIUSSS Centre-Sud-de-l'île-de-Montréal, Montreal, Quebec, Canada
| | - Florence B Pomares
- School of Health, Concordia University, Centre de recherches de l'Institut universitaire de gériatrie de Montréal (CRIUGM), CIUSSS Centre-Sud-de-l'île-de-Montréal, Montreal, Quebec, Canada
| | - Aurore A Perrault
- School of Health, Concordia University, Centre de recherches de l'Institut universitaire de gériatrie de Montréal (CRIUGM), CIUSSS Centre-Sud-de-l'île-de-Montréal, Montreal, Quebec, Canada
| | - Jean-Philippe Gouin
- School of Health, Concordia University, Centre de recherches de l'Institut universitaire de gériatrie de Montréal (CRIUGM), CIUSSS Centre-Sud-de-l'île-de-Montréal, Montreal, Quebec, Canada
| | - Jitka Bušková
- Third Faculty of Medicine, Charles University, National Institute of Mental Health, Prague, Czech Republic
| | - Karolina Janků
- National Institute of Mental Health, Klecany, Czech Republic
| | - Alexandros Vgontzas
- College of Medicine, Penn State Health Milton S. Hershey Medical Center, Sleep Research &Treatment Center, Department of Psychiatry, Pennsylvania State University, Hershey, Pennsylvania, USA
| | - Julio Fernandez-Mendoza
- College of Medicine, Penn State Health Milton S. Hershey Medical Center, Sleep Research &Treatment Center, Department of Psychiatry, Pennsylvania State University, Hershey, Pennsylvania, USA
| | - Celyne H Bastien
- School of Psychology and Centre de Recherche CERVO, Université Laval, Québec, Quebec, Canada
| | - Dieter Riemann
- Department of Psychiatry and Psychotherapy, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Chiara Baglioni
- Human Sciences Department, University of Rome Guglielmo Marconi, Rome, Italy
| | - Giacomo Carollo
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
| | - Francesca Casoni
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
| | - Marco Zucconi
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
| | - Vincenza Castronovo
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
| | - Andrea Galbiati
- Vita-Salute San Raffaele University, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
| | - Luigi Ferini-Strambi
- Vita-Salute San Raffaele University, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology-Sleep Disorders Center, Milan, Italy
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Steinmetz L, Simon L, Baumeister H, Spiegelhalder K, Terhorst Y. Treatment effect heterogeneity of cognitive behavioral therapy for insomnia - A meta-analysis. Sleep Med Rev 2024; 77:101966. [PMID: 38850594 DOI: 10.1016/j.smrv.2024.101966] [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: 02/15/2024] [Revised: 05/18/2024] [Accepted: 05/30/2024] [Indexed: 06/10/2024]
Abstract
Investigation of the heterogeneity of the treatment effect (HTE) might guide the optimization of cognitive behavioral therapy for insomnia (CBT-I). This study examined HTE in CBT-I thereby analyzing if treatment setting, control group, different CBT-I components, and patient characteristics drive HTE. Randomized controlled trials investigating CBT-I were included. Bayesian random effect meta-regressions were specified to examine variances between the intervention and control groups regarding post-treatment symptom severity. Subgroup analyses analyzing treatment setting and control groups and covariate analysis analyzing treatment components and patient characteristics were specified. No significant HTE in CBT-I was found for the overall data set, settings and control groups. The covariate analyses yielded significant results for baseline severity and the treatment component relaxation therapy. Thus, this study identified potential causes for HTE in CBT-I for the first time, showing that it might be worthwhile to further examine possibilities for precision medicine in CBT-I.
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Affiliation(s)
- Lisa Steinmetz
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.
| | - Laura Simon
- Department of Clinical Psychology and Psychotherapy, Institute of Psychology and Education, Ulm University, Ulm, Germany
| | - Harald Baumeister
- Department of Clinical Psychology and Psychotherapy, Institute of Psychology and Education, Ulm University, Ulm, Germany
| | - Kai Spiegelhalder
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Yannik Terhorst
- Department of Clinical Psychology and Psychotherapy, Institute of Psychology and Education, Ulm University, Ulm, Germany; Department of Psychology, Ludwig Maximilian University of Munich, Germany
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Wang S, Jülich ST, Lei X. Latent profile of the insomnia severity index: A longitudinal study. Sleep Med 2024; 115:202-209. [PMID: 38368737 DOI: 10.1016/j.sleep.2024.02.027] [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: 12/15/2023] [Revised: 02/01/2024] [Accepted: 02/13/2024] [Indexed: 02/20/2024]
Abstract
STUDY OBJECTIVES To identify the distinct classification of insomnia symptoms and to explore their association with sleep problems and depression. METHODS Latent profile analysis was used to examine patterns of insomnia symptoms in two samples. Discovery and replication samples comprised 1043 (Mean age at baseline = 18.95 ± 0.93 years, 62.2% females) and 729 (Mean age at baseline = 18.71 ± 1.02 years, 66.4% females) college students, respectively. Participants completed measures of sleep problems (insomnia symptoms, sleep quality, susceptibility to insomnia, perceived consequences of insomnia, dream recall frequency, and percentage of recurring nightmares) and other psychological variables (rumination and depression). Binary logistic regression was used to analyze the effects of different types of insomnia symptoms at baseline on sleep problems and depression two years later. RESULTS Four classes of insomnia symptoms were identified, and classified as "non-insomnia" (class 1, 45.7%), "mild subjective symptoms but severe subjective feelings" (class 2, 23.9%), "severe subjective symptoms but mild subjective feelings" (class 3, 22.0%), and "high insomnia risk" (class 4, 8.4%), respectively. Compared with the group classified as non-insomnia group, other classifications significantly predicted insomnia two years later, only class 4 significantly predicted depression, and class 3 significantly predicted susceptibility to insomnia, after adjusting gender, insomnia, depression, and susceptibility to insomnia at baseline. CONCLUSIONS The findings highlighted the importance of identifying the patterns of insomnia symptoms, and the need for tailored intervention to improve sleep problems. Additionally, when screening for insomnia symptoms, simplified screening using Insomnia Severity Index (ISI) dimensions or items should be considered.
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Affiliation(s)
- Shuo Wang
- Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing, 400715, China; Key Laboratory of Cognition and Personality, Southwest University, Ministry of Education, Chongqing, 400715, China
| | - Simon Theodor Jülich
- Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing, 400715, China; Key Laboratory of Cognition and Personality, Southwest University, Ministry of Education, Chongqing, 400715, China
| | - Xu Lei
- Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing, 400715, China; Key Laboratory of Cognition and Personality, Southwest University, Ministry of Education, Chongqing, 400715, China.
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Bakker MH, Oldejans NA, Hugtenburg JG, van der Horst HE, Slottje P. Insomnia management in Dutch general practice: a routine care database study. Scand J Prim Health Care 2023; 41:306-316. [PMID: 37470474 PMCID: PMC10478592 DOI: 10.1080/02813432.2023.2237073] [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: 03/15/2023] [Accepted: 07/11/2023] [Indexed: 07/21/2023] Open
Abstract
OBJECTIVE To explore insomnia management in general practice, with a focus on sleep medication prescription. DESIGN Descriptive analysis of anonymized routine general practice care data extracted from electronic medical records (EMRs), including demographics, free text annotations from sleep consultations and sleep medication prescriptions covering one year before up to two years after the registration of the International Classification for Primary Care (ICPC) code P06 'Sleep disturbance'. SETTING Twenty-one general practices in an urban area of the Netherlands. PATIENTS Adults (18-85 year) with a first sleep consultation with their GP. OUTCOMES Documented non-pharmacological and sleep medication treatment. RESULTS Of the 1,089 patients who consulted their general practitioner (GP) for sleep disturbance for the first time, about 50% had one more sleep consultation during the two years follow-up. Over two years including the first consultation, GPs documented a non-pharmacological intervention for 48.4% of the patients and prescribed sleep medication to 77.0%. 64.6% of the patients received a sleep medication prescription in the first consultation. Among patients receiving medication (N = 838); 59.6% received more than one prescription; 76.8% received one or more short-acting benzodiazepine receptor agonist (BZRA), 39.5% one or more unrecommended drugs and 14.7% >180 pills of BZRAs in two years. CONCLUSION Although the guidelines advocate non-pharmacological treatment and warn against unwarranted sleep medication, it is still very common in Dutch general practice to prescribe medication, even at the first sleep consultation. Prescriptions frequently include unrecommended and off-label drugs or repeated BZRA prescriptions.
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Affiliation(s)
- Mette H. Bakker
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands
| | - Nina A. Oldejans
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Jacqueline G. Hugtenburg
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands
- Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Henriëtte E. van der Horst
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands
| | - Pauline Slottje
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands
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O’Regan D, Garcia-Borreguero D, Gloggner F, Wild I, Leontiou C, Ferini-Strambi L. Mapping the insomnia patient journey in Europe and Canada. Front Public Health 2023; 11:1233201. [PMID: 37711247 PMCID: PMC10497771 DOI: 10.3389/fpubh.2023.1233201] [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: 06/01/2023] [Accepted: 08/11/2023] [Indexed: 09/16/2023] Open
Abstract
Introduction Insomnia affects daily functioning and overall health, and is thus associated with significant individual, societal, and economic burden. The experience of patients living with insomnia, their perception of the condition, and its impact on their quality of life is not well documented. The objective of this study was to map the patient journey in insomnia and identify unmet needs. Methods Participants were individuals with insomnia, and healthcare professionals (HCPs) who treat insomnia, in the United Kingdom, France, Germany, Italy, and Canada. Qualitative interviews (50 patients, 70 HCPs) and a quantitative survey (700 patients, 723 HCPs) were conducted to inform the patient-journey mapping and obtain information on the emotions, perceptions, and experiences of patients and HCPs. Results The patient journey comprises seven phases. The first defines the onset of insomnia symptoms. Phase 2 represents self-initiated behavior change to improve sleep (e.g., sleep hygiene, reducing caffeine, exercise). The next phase is characterized by use of over-the-counter (OTC) treatments, which generally fail to provide lasting relief. Phase 4 describes the first HCP consultation (occurring several months to several years after onset) and typically occurs at a crisis point for the patient; patients may be looking for an immediate solution (e.g., medication), which may not align with their HCP's recommendation. The following stage comprises sleep hygiene/behavioral changes (±OTC treatment) under HCP guidance for many patients, although offering prescription treatments without a sleep hygiene stage under supervision is more common in some countries. Phase 6 describes prescription medication initiation, where patients fluctuate between relief/hopefulness and a sense of failure, while HCPs try to balance the need to provide relief for the patient while maintaining best medical practice and minimizing adverse effects. The final phase (living with long-term insomnia) represents an indefinite period during which sleep issues remain unresolved for many patients, with most of them continuing to use prescription treatments for longer than indicated and creating their own variable, self-managed regimens combining multiple modalities. Conclusion This patient journey analysis for insomnia revealed seven distinct phases, highlighting different touchpoints where insomnia management could be optimized.
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Affiliation(s)
- David O’Regan
- Sleep Disorders Centre, Guy’s Hospital, London, United Kingdom
- Faculty of Life Sciences and Medicine, King’s College, London, United Kingdom
| | | | | | - Imane Wild
- Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland
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Shin JW, Kim S, Shin YJ, Park B, Park S. Comparison of Acceptance and Commitment Therapy (ACT) and Cognitive Behavior Therapy (CBT) for Chronic Insomnia: A Pilot Randomized Controlled Trial. Nat Sci Sleep 2023; 15:523-531. [PMID: 37431325 PMCID: PMC10329838 DOI: 10.2147/nss.s409981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/22/2023] [Indexed: 07/12/2023] Open
Abstract
Purpose Acceptance and Commitment Therapy (ACT) is part of the third wave of cognitive behavior therapy, and has six core components: acceptance, cognitive defusion, self as context, being present, values, and committed behavior. This study aimed to examine the efficacy of ACT for insomnia compared with cognitive behavior therapy for insomnia (CBT-I) in patients with chronic primary insomnia. Methods The study recruited patients with chronic primary insomnia from a university hospital between August 2020 and July 2021. Thirty patients were enrolled and randomly assigned to receive either ACT (n = 15) or CBT-I (n = 15). Interventions were performed over four weeks, with four sessions of face-to-face therapy and four sessions of online therapy. The outcomes were measured using a sleep diary and a questionnaire. Results Post-intervention, the ACT and CBT-I groups had significantly improved sleep quality, insomnia severity, depression, beliefs about sleep, sleep onset latency (SOL), and sleep efficacy (SE) (p < 0.05). However, anxiety was significantly reduced in the ACT group (p = 0.015), but not in the CBT-I group. Conclusion ACT had a significant effect on primary insomnia and secondary symptoms, especially anxiety related to insomnia. These findings suggest that ACT could be a potential intervention for individuals who do not respond to CBT-I, who have high anxiety regarding sleep problems.
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Affiliation(s)
- Jung-Won Shin
- Department of Neurology, Memory Center, Bundang CHA Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Seonyeop Kim
- Graduate School of Clinical Counselling Psychology, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Yoon Jung Shin
- Graduate School of Clinical Counselling Psychology, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Bomi Park
- Graduate School of Clinical Counselling Psychology, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Sunyoung Park
- Graduate School of Clinical Counselling Psychology, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
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Bakker MH, Hugtenburg JG, Smits MG, van der Horst HE, Slottje P. Off-label low dose amitriptyline for insomnia disorder: Patient-reported outcomes. Pharmacoepidemiol Drug Saf 2023; 32:435-445. [PMID: 36309966 DOI: 10.1002/pds.5561] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/15/2022] [Accepted: 10/26/2022] [Indexed: 11/12/2022]
Abstract
PURPOSE Low dose amitriptyline is prescribed off-label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to assess patient-reported treatment effect and side effects of low dose amitriptyline for insomnia in routine care data. METHODS Cross-sectional study: Seven hundred fifty-two consecutive patients with insomnia disorder having sleep maintenance problems were treated in an outpatient sleep clinic with low dose amitriptyline (10-20 mg based on self-titration). Treatment was intended to improve sleep maintenance. Before the planned follow-up consultation (approximately 6 weeks after start treatment) patients completed an online treatment evaluation questionnaire. Treatment (dose, adherence), sleep, fatigue, satisfaction and side effects were assessed by multiple-choice questions with room for free-text elaboration. RESULTS 53.7% of the patients reported to use amitriptyline up to 10 mg/day, 42.9% used a self-increased dose of mostly 20 mg/day, while 3.5% had discontinued treatment. 73.9% of the total study population reported improvement of sleep maintenance, 31.3% improved sleep onset, 35.2% improved daytime fatigue, and 45.8% reported to be (very) satisfied with treatment results. 66.1% reported at least one side effect. The reported side effects were generally the already known side effects of amitriptyline. CONCLUSION These patient-reported outcomes support the clinical observations that low dose amitriptyline improves sleep maintenance on the short term and that it is generally well tolerated. This further justifies randomized controlled trials in patients with insomnia disorder and sleep maintenance problems to assess the effectiveness and safety of low dose amitriptyline on the short and long term.
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Affiliation(s)
- Mette H Bakker
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Research programme Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - Jacqueline G Hugtenburg
- Research programme Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
- Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Marcel G Smits
- Multidisciplinary Expertise Centre for Sleep-Wake Disorders and Chronobiology, Gelderse Vallei Hospital, Ede, Netherlands
| | - Henriëtte E van der Horst
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Research programme Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - Pauline Slottje
- Department of General Practice, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Research programme Quality of Care, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
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Hrozanova M, Meisingset I, Kallestad H, Pallesen S, Nordstoga AL, Skarpsno ES. Group-delivered cognitive behavioural therapy versus waiting list in the treatment of insomnia in primary care: study protocol for a pragmatic, multicentre randomized controlled trial. BMC PRIMARY CARE 2023; 24:61. [PMID: 36864376 PMCID: PMC9979487 DOI: 10.1186/s12875-023-02018-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 02/23/2023] [Indexed: 03/04/2023]
Abstract
BACKGROUND Insomnia is common in the general population and is a risk factor for ill-health, which highlights the importance of treating insomnia effectively and cost-efficiently. Cognitive-behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment due to its long-term effectiveness and few side-effects, but its availability is limited. The aim of this pragmatic, multicentre randomized controlled trial is to investigate the effectiveness of group-delivered CBT-I in primary care compared to a waiting-list control group. METHODS A pragmatic multicentre randomized controlled trial will be conducted with about 300 participants recruited across 26 Healthy Life Centres in Norway. Participants will complete online screening and provide consent before enrolment. Those who meet the eligibility criteria will be randomized to a group-delivered CBT-I or to a waiting list according to a 2:1 ratio. The intervention consists of four two-hour sessions. Assessments will be performed at baseline, 4 weeks, 3- and 6 months post-intervention, respectively. The primary outcome is self-reported insomnia severity at 3 months post-intervention. Secondary outcomes include health-related quality of life, fatigue, mental distress, dysfunctional beliefs and attitudes about sleep, sleep reactivity, 7-day sleep diaries, and data obtained from national health registries (sick leave, use of relevant prescribed medications, healthcare utilization). Exploratory analyses will identify factors influencing treatment effectiveness, and we will conduct a mixed-method process evaluation to identify facilitators and barriers of participants' treatment adherence. The study protocol was approved by the Regional Committee for Medical and Health Research ethics in Mid-Norway (ID 465241). DISCUSSION This large-scale pragmatic trial will investigate the effectiveness of group-delivered cognitive behavioural therapy versus waiting list in the treatment of insomnia, generating findings that are generalizable to day-to-day treatment of insomnia in interdisciplinary primary care services. The trial will identify those who would benefit from the group-delivered therapy, and will investigate the rates of sick leave, medication use, and healthcare utilization among adults who undergo the group-delivered therapy. TRIAL REGISTRATION The trial was retrospectively registered in the ISRCTN registry (ISRCTN16185698).
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Affiliation(s)
- Maria Hrozanova
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
| | - Ingebrigt Meisingset
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.,Unit for Physiotherapy Services, Trondheim Municipality, Trondheim, Norway
| | - Håvard Kallestad
- Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.,Department of Mental Health Care, St. Olavs Hospital, Trondheim, Norway
| | - Ståle Pallesen
- Department of Psychosocial Science, University of Bergen, Bergen, Norway.,Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway
| | - Anne Lovise Nordstoga
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.,Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim, Norway
| | - Eivind Schjelderup Skarpsno
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.,Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim, Norway
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Shin JW, Kim S, Park B, Shin YJ, Park S. Improving mental health and daytime function in adult insomnia patients predict cognitive behavioral therapy for insomnia effectiveness: A case-control study. Sleep Med X 2023; 5:100071. [PMID: 37090917 PMCID: PMC10119957 DOI: 10.1016/j.sleepx.2023.100071] [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] [Received: 07/18/2022] [Revised: 02/16/2023] [Accepted: 03/23/2023] [Indexed: 04/03/2023] Open
Abstract
Objective This study investigated demographic, sleep related symptoms and mental health status as predictors of clinically significant treatment responses to cognitive behavioral therapy in adults who have good adherence for the cognitive behavioral therapy for insomnia (CBT-I) program in primary insomnia. Methods A total of 42 adults with primary insomnia disorder were treated with CBT-I at a university hospital from June 2020 to January 2021. Demographic variables were surveyed and sleep-related symptoms were measured using self-reported questionnaires before and after the intervention, comprising a 6-week interval. The treatment responder group was defined as patients with an Insomnia Severity Index change score >7 compared to baseline. Logistic regression and paired t-test examined whether these factors predicted treatment outcomes for CBT-I. Results Demographic variables did not predict treatment outcomes. Higher levels of anxiety were associated with a higher likelihood of treatment response (odds ratio [OR] = 1.234; confidence interval [CI]: 1.008-1.511). More severe insomnia at baseline was associated with a greater likelihood of treatment response (OR = 1.450; CI: 1.121-1.875). The lesser the dysfunctional beliefs and attitudes about sleep, the more effective the treatment response (OR = 0.943; CI: 0.904-0.984). Unlike the group of treatment responders, daytime function, depressive mood, and anxiety status did not improve in the group of treatment non-responders after CBT-I intervention. Conclusions Patients with severe insomnia and anxiety at baseline should be treated more aggressively with CBT-I. During treatment, patients' mental health problems and daytime activities should be continuously monitored, in order to help improve these problems which might strengthen the effectiveness of CBT-I.
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Affiliation(s)
- Jung-Won Shin
- Department of Neurology, Memory center, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
- Corresponding author. Department of Neurology, CHA Bundang Medical Center, CHA University, 59 Yatap-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-712, Republic of Korea.
| | - Seonyeop Kim
- Graduate School of Clinical Counselling Psychology, CHA university, Seongnam, Republic of Korea
| | - Bomi Park
- Graduate School of Clinical Counselling Psychology, CHA university, Seongnam, Republic of Korea
| | - Yoon Jung Shin
- Graduate School of Clinical Counselling Psychology, CHA university, Seongnam, Republic of Korea
| | - Sunyoung Park
- Graduate School of Clinical Counselling Psychology, CHA university, Seongnam, Republic of Korea
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Abstract
Cognitive behavioral therapy for insomnia (CBT-I) is the universally recommended treatment of choice for insomnia disorder based on its safety and posttreatment durability of benefit. However, CBT-I does not help all patients achieve remission. The second most evidence-based treatment, hypnotic pharmacotherapy (PCT), does not resolve perpetuating factors of insomnia, resulting in potential waning of benefit and dependence. This article presents a rationale that supports consideration of hypnotic augmentation of CBT-I (COMB), along with a review of select randomized controlled trials relevant to clinical decision-making.
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12
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Guided Internet-Based Cognitive Behavioral Therapy for Insomnia: Prognostic and Treatment-Predictive Factors. Diagnostics (Basel) 2023; 13:diagnostics13040781. [PMID: 36832269 PMCID: PMC9955838 DOI: 10.3390/diagnostics13040781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/08/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Understanding which factors predict the outcome of internet-based cognitive behavioral therapy for insomnia (iCBT-I) may help to tailor this intervention to the patient's needs. We have conducted a secondary analysis of a randomized, controlled trial comparing a multicomponent iCBT-I (MCT) and an online sleep restriction therapy (SRT) for 83 chronic insomnia patients. The difference in the Insomnia Severity Index from pre- to post-treatment and from pre-treatment to follow-up at 6 months after treatment was the dependent variable. Prognostic and treatment-predictive factors assessed at baseline were analyzed with multiple linear regression. The shorter duration of insomnia, female gender, high health-related quality of life, and the higher total number of clicks had prognostic value for a better outcome. Other factors were found to be prognostic for outcome at the follow-up assessment: treatment with benzodiazepines, sleep quality, and personal significance of sleep problems. A high level of dysfunctional beliefs and attitudes about sleep (DBAS) was a moderator for better effects in the MCT at post-treatment assessment. Various prognostic factors (e.g., duration of insomnia, gender, or quality of life) may influence the success of treatment. The DBAS scale may be recommended to select patients for MCT rather than SRT.
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13
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Porosnicu Rodriguez KA, Salas RME, Schneider L. Insomnia. Neurol Clin 2022; 41:1-19. [DOI: 10.1016/j.ncl.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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14
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Proteomics Reveals Molecular Changes in Insomnia Patients with More Dreams. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:6181943. [PMID: 35432581 PMCID: PMC9012652 DOI: 10.1155/2022/6181943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/10/2022] [Accepted: 03/18/2022] [Indexed: 11/17/2022]
Abstract
Background Insomnia is a sleep disorder and the cause of many healthy problems. However, there are few studies on patients with insomnia and dreaminess at present. Therefore, this study is aimed at exploring the pathological molecular mechanisms and potential diagnostic and therapeutic targets related to insomnia patients with more dreams. Methods Sleep characteristics of 36 primary insomnia patients with more dreams and 36 well sleeping participants were assessed using polysomnography (PSG) and Pittsburgh Sleep Quality Index (PSQI). Serum samples from 9 insomnia patients and 9 controls were randomly selected for proteomic detection. Differentially expressed proteins (DEPs) between the two groups were identified; enrichment analysis and PPI network were performed. The top 10 most connected proteins in the PPI network were subjected to targeted drug prediction and screened key proteins. Proteins with targeted drugs were recognized as key proteins and subjected to ELISA detection. Results Insomnia patients had a distinct REM behavior disorder signature compared with controls. Proteomic sequencing identified 76 DEPs. Enrichment analysis found that DEPs were significantly enriched in the complement and coagulation cascades. Metabolic responses were also activated in insomnia patients. Among the hub proteins screened in the PPI network, APOA1, APOB, F2, and SPARC may be targeted by many herbal medicines and considered as key proteins. ELISA assays validated their differential expression between insomnia and controls. Conclusion In this study, we identified the potential key proteins of insomnia patients with more dreams. The pathological process may associate with inflammation and metabolic response. These results provide molecular targets for diagnostic and therapeutic targets. The results of our analysis suggest that the expression changes of key proteins have a good predictive diagnostic role for the occurrence of insomnia with more dreams in patients.
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15
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Kao CH, D'Rozario AL, Lovato N, Wassing R, Bartlett D, Memarian N, Espinel P, Kim JW, Grunstein RR, Gordon CJ. Insomnia subtypes characterised by objective sleep duration and NREM spectral power and the effect of acute sleep restriction: an exploratory analysis. Sci Rep 2021; 11:24331. [PMID: 34934082 PMCID: PMC8692344 DOI: 10.1038/s41598-021-03564-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 12/06/2021] [Indexed: 02/08/2023] Open
Abstract
Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.
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Affiliation(s)
- Chien-Hui Kao
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia
| | - Angela L D'Rozario
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia.,School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
| | - Nicole Lovato
- Adelaide Institute for Sleep Health, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
| | - Rick Wassing
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia.,Faculty of Medicine and Health, The University Sydney, Camperdown, Sydney, NSW, 2050, Australia
| | - Delwyn Bartlett
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia.,Faculty of Medicine and Health, The University Sydney, Camperdown, Sydney, NSW, 2050, Australia
| | - Negar Memarian
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia.,British Columba Children's Hospital Research Institute, Vancouver, Canada
| | - Paola Espinel
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia
| | - Jong-Won Kim
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia.,Department of Healthcare IT, Inje University, Inje, South Korea
| | - Ronald R Grunstein
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia.,Faculty of Medicine and Health, The University Sydney, Camperdown, Sydney, NSW, 2050, Australia.,Sleep and Severe Mental Illness Clinic, CPC-RPA Clinic, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Christopher J Gordon
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, Australia. .,Faculty of Medicine and Health, The University Sydney, Camperdown, Sydney, NSW, 2050, Australia.
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Bakker MH, Hugtenburg JG, van Straten A, van der Horst HE, Slottje P. Effectiveness of low-dose amitriptyline and mirtazapine for insomnia disorder: study protocol of a randomised, double-blind, placebo-controlled trial in general practice (the DREAMING study). BMJ Open 2021; 11:e047142. [PMID: 34475156 PMCID: PMC8413934 DOI: 10.1136/bmjopen-2020-047142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION For over more than a decade, low-dose amitriptyline and mirtazapine are prescribed off-label for insomnia. However, placebo-controlled evidence on these antidepressants for insomnia is still lacking. Therefore, the present trial aims to assess the effectiveness of low-dose amitriptyline (10-20 mg/day) and mirtazapine (7.5-15 mg/day) in patients with insomnia disorder with difficulty maintaining sleep or early-morning awakening problems in general practice. METHODS AND ANALYSIS The Drug REdiscovery: low-dose Amitriptyline and Mirtazapine for INsomnia disorder in General practice (DREAMING) study is a randomised, double-blind, placebo-controlled trial in about 50 general practices. Adults (18-85 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders-5) who ask their general practitioner (GP) for sleep medication when non-pharmacological treatment is deemed not effective, are eligible. EXCLUSION CRITERIA isolated sleep initiation problem, contraindications for or drug-drug interactions with either amitriptyline or mirtazapine. Participants (n=156) will be randomly assigned to three parallel treatment groups of 16-week treatment with either amitriptyline (one or two tablets of 10 mg/day) or mirtazapine (one or two tablets of 7.5 mg/day) or placebo (one or two tablets) alongside usual GP care. All participants start and end with single dose, but dose can be doubled following GP consultation in week 3. Questionnaire assessments will be conducted at baseline, week 6, 12, 20 and 52. The primary study outcome is self-reported insomnia severity at 6 weeks, measured with the Insomnia Severity Index (ISI) in an intention to treat analysis. Secondary outcomes include subjective sleep quality quantified by sleep indices, daytime functioning and symptoms, safety and treatment evaluation and other sleep care consumption. ETHICS AND DISSEMINATION The Medical Ethics Committee of the VU Medical Centre Amsterdam approved this trial. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders. TRIAL REGISTRATION NUMBER NTR7449.
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Affiliation(s)
- Mette H Bakker
- General Practice, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
| | | | | | | | - Pauline Slottje
- General Practice, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
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Galbiati A, Sforza M, Leitner C, Castelnovo A, D'Este G, Ferini-Strambi L, Manconi M, Castronovo V. Objective total sleep time and effectiveness of cognitive-behavioral therapy for insomnia: methodological issues. Sleep Med 2021; 85:105-106. [PMID: 34298227 DOI: 10.1016/j.sleep.2021.06.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Andrea Galbiati
- "Vita-Salute" San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology - Sleep Disorders Center, Milan, Italy.
| | - Marco Sforza
- "Vita-Salute" San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology - Sleep Disorders Center, Milan, Italy
| | - Caterina Leitner
- "Vita-Salute" San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology - Sleep Disorders Center, Milan, Italy
| | - Anna Castelnovo
- Sleep Medicine, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Lugano, Switzerland; Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
| | - Giada D'Este
- "Vita-Salute" San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology - Sleep Disorders Center, Milan, Italy
| | - Luigi Ferini-Strambi
- "Vita-Salute" San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology - Sleep Disorders Center, Milan, Italy
| | - Mauro Manconi
- Sleep Medicine, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Lugano, Switzerland; Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
| | - Vincenza Castronovo
- IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, Neurology e Sleep Disorders Center, Milan, Italy
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Depressive and stress symptoms in insomnia patients predict group cognitive-behavioral therapy for insomnia long-term effectiveness: A data-driven analysis. J Affect Disord 2021; 289:117-124. [PMID: 33979721 DOI: 10.1016/j.jad.2021.04.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/09/2021] [Accepted: 04/15/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Insomnia Disorder is characterized by high degree of phenotypic heterogeneity, that might influence treatment response. METHODS 123 of 294 insomnia patients initially recruited (66.7% females, age=40.59±11.89) were assessed before and after group Cognitive-Behavioral Therapy for Insomnia (CBT-I), as well as at follow-up (7.8±1.6 years after the end-of-treatment). By use of latent class analysis (LCA) we identified insomnia subtypes according with baseline scores of insomnia severity and features, anxiety, depression, stress and sleepiness symptoms, circadian rhythm, and treatment effectiveness (Delta score of Insomnia Severity Index-ISI between baseline and end-of-treatment). RESULTS By LCA we revealed three classes: "PURE INSOMNIA", "INSOMNIA+ANXIETY+DEPRESSION+STRESS", and "INSOMNIA+ANXIETY". The improvements in insomnia severity was maintained up to 10 years after the end-of-treatment, but with differences between classes (p<0.05). Class "INSOMNIA+ANXIETY+DEPRESSION+STRESS" showed at the end-of-treatment the largest percentage of responders (63.5% = Insomnia Severity Index decrease ≥8). However, at follow up the effect was less and 48.1% had a moderate or severe insomnia (Insomnia Severity Index >14). LIMITATIONS The lack of a control group and the absence of a complete clinical assessment at the follow-up limit the interpretability of our results. CONCLUSIONS Our data driven analysis suggest insomnia heterogeneity can be categorized into sub-classes by depression, anxiety, and stress symptoms. In addition, insomnia patients with stress and depression symptoms maintained highest percentage of clinical depression at the end-of-treatment and insomnia at follow-up, in comparison with others classes. Stress and depression symptoms should be considered risk factors that play an important role in the long-term outcome of CBT-I.
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19
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Sweetman A, Lechat B, Catcheside PG, Smith S, Antic NA, O’Grady A, Dunn N, McEvoy RD, Lack L. Polysomnographic Predictors of Treatment Response to Cognitive Behavioral Therapy for Insomnia in Participants With Co-morbid Insomnia and Sleep Apnea: Secondary Analysis of a Randomized Controlled Trial. Front Psychol 2021; 12:676763. [PMID: 34017296 PMCID: PMC8129160 DOI: 10.3389/fpsyg.2021.676763] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 04/13/2021] [Indexed: 01/16/2023] Open
Abstract
OBJECTIVE Co-morbid insomnia and sleep apnea (COMISA) is a common and debilitating condition that is more difficult to treat compared to insomnia or sleep apnea-alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia (CBTi) is effective in patients with COMISA, however, those with more severe sleep apnea and evidence of greater objective sleep disturbance may be less responsive to CBTi. Polysomnographic sleep study data has been used to predict treatment response to CBTi in patients with insomnia-alone, but not in patients with COMISA. We used randomized controlled trial data to investigate polysomnographic predictors of insomnia improvement following CBTi, versus control in participants with COMISA. METHODS One hundred and forty five participants with insomnia (ICSD-3) and sleep apnea [apnea-hypopnea index (AHI) ≥ 15] were randomized to CBTi (n = 72) or no-treatment control (n = 73). Mixed models were used to investigate the effect of pre-treatment AHI, sleep duration, and other traditional (AASM sleep macrostructure), and novel [quantitative electroencephalography (qEEG)] polysomnographic predictors of between-group changes in Insomnia Severity Index (ISI) scores from pre-treatment to post-treatment. RESULTS Compared to control, CBTi was associated with greater ISI improvement among participants with; higher AHI (interaction p = 0.011), less wake after sleep onset (interaction p = 0.045), and less N3 sleep (interaction p = 0.005). No quantitative electroencephalographic, or other traditional polysomnographic variables predicted between-group ISI change (all p > 0.09). DISCUSSION Among participants with COMISA, higher OSA severity predicted a greater treatment-response to CBTi, versus control. People with COMISA should be treated with CBTi, which is effective even in the presence of severe OSA and objective sleep disturbance.
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Affiliation(s)
- Alexander Sweetman
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Bastien Lechat
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- College of Science and Engineering, Flinders University, Adelaide, SA, Australia
| | - Peter G. Catcheside
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Simon Smith
- Institute for Social Science Research, The University of Queensland, Brisbane, QLD, Australia
| | - Nick A. Antic
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- Sleep Health Service, Repatriation General Hospital and Respiratory and Sleep Services, Southern Adelaide Local Health Network, Adelaide, SA, Australia
| | - Amanda O’Grady
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Nicola Dunn
- Thoracic Program, The Prince Charles Hospital, Chermside, QLD, Australia
| | - R. Doug McEvoy
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Leon Lack
- The Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- College of Education Psychology and Social Work, Flinders University, Adelaide, SA, Australia
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20
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Sun Y, Zhao R, Liu R, Li T, Ni S, Wu H, Cao Y, Qu Y, Yang T, Zhang C, Sun Y. Integrated Screening of Effective Anti-Insomnia Fractions of Zhi-Zi-Hou-Po Decoction via Drosophila melanogaster and Network Pharmacology Analysis of the Underlying Pharmacodynamic Material and Mechanism. ACS OMEGA 2021; 6:9176-9187. [PMID: 33842786 PMCID: PMC8028125 DOI: 10.1021/acsomega.1c00445] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/11/2021] [Indexed: 05/05/2023]
Abstract
Insomnia is an anabatic epidemiology, while the mechanism is extremely complicated; it remains one of the major scientific challenges in life sciences. Because of the advantage of having a similar genetic background and circadian rhythm as those of humans, the Drosophila melanogaster model organism is hugely popular in sleep-related drug screening studies. Seven-day-old virgin D. melanogaster was used to establish the sleep deprivation model by repeated light stimulation at night. Using PySolo activity monitoring system and Drosophila activity as indices, the effective fractions of Zhi-Zi-Hou-Po decoction (ZZHPD) for insomnia were screened; the content of monoamine neurotransmitters dopamine (DA), 5-hydroxyindole-3-acetic acid (5-HIAA), Homovanillic acid (HVA), and 5-hydroxytryptamine (5-HT) in the brain of D. melanogaster were determined by high-performance liquid chromatography-electro-chemical detection. The herb-compound-target-disease target network were further constructed through network pharmacology to identify the potential targets and pathways of ZZHPD in the intervention of insomnia. Finally, the molecular docking method was used for evaluating the binding characteristics of important compounds from ZZHPD with related targets. The results showed that a certain dose of ZZHPD and its petroleum ether, dichloromethane, ethyl acetate, and n-butanol fractions could improve sleep. The dichloromethane fraction from ZZHPD extracts showed the best anti-insomnia effect among all extracts. It can also reduce the content of DA and HVA in the brain of D. melanogaster and increase 5-HT and 5-HIAA levels. The network pharmacology showed that the main active ingredients in ZZHPD included magnolol, honokiol, hesperidin, and so forth. According to the screening conditions, there were 71 targets and the result of KEGG enrichment analysis revealed that 73 pathways were associated with insomnia, which were primarily involved in inflammatory response, central neurotransmitter regulation, and apoptosis to relieve insomnia. The molecular docking results clarified that naringenin and apigenin have an intimate relationship with GABAA receptor, histamine H1, orexin receptor type 2, and interleukin-6. The mechanism of relieving insomnia is the result of the interaction of multi-components, multi-targets, and multi-pathways, which provides a certain theoretical basis for the treatment of insomnia and related diseases as well as clinical research.
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