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Kezuka D, Isogaya Y, Matsubara K, Suzuki C, Suzuki E. Comparison of bipolar disorder patients' evaluation of their treatment in 2015 and 2022. PCN REPORTS : PSYCHIATRY AND CLINICAL NEUROSCIENCES 2025; 4:e70109. [PMID: 40321469 PMCID: PMC12045783 DOI: 10.1002/pcn5.70109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 04/08/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025]
Affiliation(s)
- Dai Kezuka
- Division of PsychiatryTohoku Medical and Pharmaceutical UniversitySendaiJapan
- Department of PsychiatryTohoku Medical and Pharmaceutical University HospitalSendaiJapan
| | - Yuko Isogaya
- Department of PsychiatryTohoku Medical and Pharmaceutical University HospitalSendaiJapan
| | - Koki Matsubara
- Department of PsychiatryTohoku Medical and Pharmaceutical University HospitalSendaiJapan
| | - Chiho Suzuki
- The Japanese Alliance of Bipolar DisorderTokyoJapan
| | - Eiji Suzuki
- Division of PsychiatryTohoku Medical and Pharmaceutical UniversitySendaiJapan
- Department of PsychiatryTohoku Medical and Pharmaceutical University HospitalSendaiJapan
- The Japanese Alliance of Bipolar DisorderTokyoJapan
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Fico G, Bort M, Gonzalez-Campos M, D'Alessandro G, De Prisco M, Oliva V, Anmella G, Sommerhoff C, Vieta E, Murru A. Predominant Polarity for Enhanced Phenotyping and Personalized Treatment of Bipolar Disorder: A Narrative Review on Recent Findings. Curr Psychiatry Rep 2025; 27:221-230. [PMID: 40032711 PMCID: PMC12003578 DOI: 10.1007/s11920-025-01592-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2025] [Indexed: 03/05/2025]
Abstract
PURPOSE OF REVIEW This paper explores Predominant Polarity (PP) in Bipolar Disorder (BD), defined as the predominance of either manic or depressive episodes over a patient's course of illness. We examine its clinical relevance, neurobiological foundations, and potential for guiding personalized treatment strategies. The review seeks to determine whether PP is a reliable course specifier and how it can be utilized to improve clinical outcomes. RECENT FINDINGS PP has a significant impact on prognosis and treatment planning in BD. Manic and depressive PP are associated with distinct clinical and neurobiological profiles of BD, while individuals without a clear predominance of either episode type represent a more severe to-treat subgroup of patients. The development of the Polarity Index (PI) facilitates treatment decisions based on PP. PP offers a valuable framework for refining BD treatment and understanding its complexity. Future research should focus on refining PP definitions, validating neurobiological markers, and integrating these insights into comprehensive treatment models to improve patient outcomes.
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Affiliation(s)
- Giovanna Fico
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Bort
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
| | - Meritxell Gonzalez-Campos
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
| | - Giulia D'Alessandro
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Psychiatric Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56121, Pisa, Italy
| | - Michele De Prisco
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
| | - Vincenzo Oliva
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
| | - Gerard Anmella
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
| | - Constanza Sommerhoff
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
| | - Eduard Vieta
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain.
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain.
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain.
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
| | - Andrea Murru
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences (UBNeuro), University of Barcelona (UB), C. Casanova, 143, Barcelona, Catalonia, 08036, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), c. Villarroel, 170, Barcelona, Catalonia, 08036, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
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Gitlin M, Bauer M. Lithium: current state of the art and future directions. Int J Bipolar Disord 2024; 12:40. [PMID: 39609318 PMCID: PMC11604892 DOI: 10.1186/s40345-024-00362-7] [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: 08/26/2024] [Accepted: 11/18/2024] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND Lithium is our oldest continuously prescribed medication in psychopharmacology, with its history as an agent for treating mood disorders extending from the 19th century. Although clinicians prescribe it less frequently than in the past, its utility in treating bipolar disorder is unquestionable. Novel potential indications for its use in psychiatry have created excitement about broader roles for lithium in treating and preventing other disorders. CONTENT Lithium is effective both in treating acute mania, as an adjunctive antidepressant, and as a maintenance treatment in bipolar disorder. Lithium has also shown some efficacy in treating and preventing unipolar depression, but less clearly than for bipolar maintenance treatment and acute mania. Common side effects include nausea, polyuria, tremor, weight gain and cognitive dulling. These side effects are typically manageable with reasonable clinical strategies. Lithium affects renal, thyroid and parathyroid function. With clinical monitoring, these effects are easily managed although infrequent cases of severe renal insufficiency may occur with long term use. Although not all studies are positive, a consistent database suggests the efficacy of lithium in decreasing suicide attempts and suicides, likely due to its effect on impulsivity and aggression as well as its prophylaxis against depressive and manic recurrences. Recent data have suggested lithium's potential efficacy for a number of new clinical indications. Lithium's neuroprotective effects suggest potential efficacy in preventing mild cognitive impairment (MCI) and dementia as well as in aiding recovery from strokes. Higher (but still trace) lithium levels in drinking water are associated with lower rates of dementia. It is still not clear how much lithium-and what serum lithium levels- are required for either of these effects. Other preliminary research suggests that lithium may also have antiviral effects and may decrease cancer risk. CONCLUSIONS Lithium continues to be the mainstay treatment of mood disorders in general and in bipolar disorder specifically. Other potential clinical uses for lithium in psychiatry have re-invigorated excitement for research in other areas such as suicide, preventing cognitive impairment and possibly preventing viral infections and diminishing cancer risk.
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Affiliation(s)
- Michael Gitlin
- Department of Psychiatry, Geffen School of Medicine at UCLA, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA, 90095, USA.
| | - Michael Bauer
- Department of Psychiatry, Carl Gustav Carus University Hospital, Medical Faculty, Technische Universität Dresden, Dresden, Germany
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Lin YW, Chen YCB, Hung KC, Liang CS, Tseng PT, Carvalho AF, Vieta E, Solmi M, Lai ECC, Lin PY, Hsu CW, Tu YK. Efficacy and acceptability of lurasidone for bipolar depression: a systematic review and dose-response meta-analysis. BMJ MENTAL HEALTH 2024; 27:e301165. [PMID: 39557452 PMCID: PMC11574478 DOI: 10.1136/bmjment-2024-301165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 10/22/2024] [Indexed: 11/20/2024]
Abstract
QUESTION The optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose-response relationship for efficacy, acceptability, and metabolic/endocrine profiles. STUDY SELECTION AND ANALYSIS Five databases and grey literature published until 1 August 2024, were systematically reviewed. The outcomes included efficacy (changes in depression, anxiety, clinical global impression, disability and quality of life), acceptability (dropout, manic switch, suicidality and side effects) and metabolic/endocrine profiles (changes in body weight, glucose, lipid and prolactin levels). Effect sizes were calculated using a one-step dose-response meta-analysis, expressed as standardised mean differences (SMDs), risk ratios (RRs) and mean differences (MDs) with 95% CIs. FINDINGS Five randomised clinical trials (2032 patients, mean treatment duration 6 weeks) indicated that the optimal therapeutic dose of lurasidone (40-60 mg) improved depression (50 mg: SMD -0.60 (95% CI -0.30, -0.89)), anxiety (50 mg: -0.32 (95% CI -0.21, -0.42)), clinical global impression (50 mg: -0.67 (95% CI -0.30, -1.03)) and disability (50 mg: -0.38 (95% CI -0.08, -0.69)). Side effects increased with higher doses (50 mg: RR 1.15 (95% CI 1.05, 1.25); 100 mg: 1.18 (95% CI 1.02, 1.36)), but dropout, manic switch and suicidality did not show a dose-effect relationship. Weight increased at doses<60 mg (40 mg: MD 0.38 (95% CI 0.16, 0.60) kg), while blood glucose levels rose at doses>70 mg (100 mg: 3.16 (95% CI 0.76, 5.57) mg/dL). Prolactin levels increased in both males (50 mg: 3.21 (95% CI 1.59, 4.84) ng/mL; 100 mg: 5.61 (95% CI 2.42, 8.81)) and females (50 mg: 6.64 (95% CI 3.50, 9.78); 100 mg: 5.33 (95% CI 0.67, 10.00)). CONCLUSIONS A daily dose of 40-60 mg of lurasidone is a reasonable choice for bipolar depression treatment. TRIAL REGISTRATION NUMBER INPLASY202430069.
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Affiliation(s)
- Yu-Wei Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yang-Chieh Brian Chen
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chuan Hung
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Sung Liang
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan
| | - Ping-Tao Tseng
- Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
- Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan
- Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan
| | - Andre F Carvalho
- Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clinic, IDIBAPS, CIBERSAM, Institute of Neuroscience, University of Barcelona, Barcelona, Catalonia, Spain
| | - Marco Solmi
- Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada
- Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute (OHRI), Clinical Epidemiology Program, University of Ottawa, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
| | - Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Population Health Data Center, National Cheng Kung University, Tainan, Taiwan
| | - Pao-Yen Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Kang Tu
- Institute of Health Data Analytics & Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
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Rybakowski JK. Lithium: Fifteen Years Later. Neuropsychobiology 2024; 83:205-213. [PMID: 39510063 DOI: 10.1159/000542490] [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: 07/20/2024] [Accepted: 11/02/2024] [Indexed: 11/15/2024]
Abstract
BACKGROUND The 75th anniversary of introducing lithium into modern psychiatry is recognized, attested by the 1949 paper of John Cade. About this event, my editorial in the special 2010 issue of Neuropsychobiology was titled "Lithium: Sixty Years Thereafter." Since then, fifteen more years have brought further information about lithium. This paper makes a narrative review of the most important articles published in this period. SUMMARY The selected key literature of 2010-2024 addressed lithium prophylactic efficacy in bipolar disorder (BD), including pediatric, recurrent depression, and lithium augmentation of antidepressants in treatment-resistant depression (TRD). Novel data have been obtained for lithium adverse effects (kidney, thyroid) and beneficial outcomes of long-term lithium administration (anti-suicidal, neuroprotective, antiviral, and others). The results on the mechanisms of lithium action covered genetic investigations of the Consortium of Lithium Genetics (ConLiGen) and in vitro studies with induced pluripotent stem cells and lymphoblastoid cell lines. The underutilization of lithium nowadays was emphasized, and the ways to overcome it were considered. KEY MESSAGES Lithium remains the choice drug for recurrence prevention in BD, also in adolescents, and a significant option for augmentation of antidepressants in TRD. The adverse side effects should be carefully followed and managed according to current guidelines. There are also beneficial lithium impacts, of which anti-suicidal and anti-dementia seem the most important. Most of the results of neurobiological studies on lithium mechanisms may be related to lithium response and some (e.g., immunomodulatory) to the pathogenesis of BD. Better education about lithium could make more patients the beneficiary of this drug.
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Affiliation(s)
- Janusz K Rybakowski
- Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
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Belzeaux R, Gressier F, Boudieu L, Arnould A, Moreau E, Pastol J, Tzavara E, Sutter-Dallay AL, Samalin L. French Society for Biological Psychiatry and Neuropsychopharmacology and French-speaking Marcé Society guidelines for the management of mood disorders in women before, during, and after pregnancy. Arch Womens Ment Health 2024; 27:595-605. [PMID: 38367037 DOI: 10.1007/s00737-024-01440-6] [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: 10/13/2023] [Accepted: 02/01/2024] [Indexed: 02/19/2024]
Abstract
PURPOSE The French Society for Biological Psychiatry and Neuropsychopharmacology and the French-speaking Marcé Society have joined forces to establish expert recommendations on the prescription of psychotropic drugs before, during, and after pregnancy in women with major depressive disorder (MDD) and bipolar disorder (BD). METHODS To elaborate recommendations, we used the RAND/UCLA Appropriateness Method, which combines scientific evidence and expert clinicians' opinions. A written survey was completed by 48 psychiatrists, who have expertise in the management of mood disorders and/or in perinatal psychiatry. Key recommendations are provided by the scientific committee based on data analysis and interpretation of the results of the survey. RESULTS The recommendations address the following three areas that are deemed essential in women with mood disorders, with an emphasis on screening, treatment options, and monitoring: (i) management of mood disorders in women of childbearing age, (ii) management during pregnancy, (iii) management during the post-partum period. As first-line strategies, experts recommend treating mood symptoms during pregnancy and maintaining a pharmacological treatment, even in euthymic or stabilized patients. First-line options include only medications with no teratogenic risk, and during breastfeeding, only medications without evidence of adverse effects in nursing infants. CONCLUSION The expert consensus guidelines will help facilitate treatment decisions for clinicians in the daily assessment and management of mood disorders in women of childbearing age, during pregnancy, and in the post-partum period.
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Affiliation(s)
- Raoul Belzeaux
- French Society for Biological Psychiatry and Neuropsychopharmacology, Saint Germain en Laye, France.
- Pôle Universitaire de Psychiatrie, CHU de Montpellier, 39 Avenue C. Flahaut, 34090, Montpellier, France.
| | - Florence Gressier
- Société Marcé Francophone, Chatenay Malabry, France
- Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Hôpital de Bicêtre, Université Paris-Saclay, Equipe Moods, INSERM, UMR-1018, CESP, Le Kremlin Bicêtre, France
| | - Ludivine Boudieu
- Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal, (UMR 6602), Clermont-Ferrand, France
| | - Adeline Arnould
- French Society for Biological Psychiatry and Neuropsychopharmacology, Saint Germain en Laye, France
- Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal, (UMR 6602), Clermont-Ferrand, France
| | - Elsa Moreau
- French Society for Biological Psychiatry and Neuropsychopharmacology, Saint Germain en Laye, France
- Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Julia Pastol
- French Society for Biological Psychiatry and Neuropsychopharmacology, Saint Germain en Laye, France
- Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - Eleni Tzavara
- Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France
- Université Paris Cité, CNRS, UMR 8002 INCC, Paris, France
| | - Anne Laure Sutter-Dallay
- Société Marcé Francophone, Chatenay Malabry, France
- BPHRC INSERM 1219, HEALTHY Team, Bordeaux University, Bordeaux, France
- Perinatal Psychiatry Network, University Department of Child and Adolescent Psychiatry, Charles Perrens Hospital, Bordeaux, France
| | - Ludovic Samalin
- French Society for Biological Psychiatry and Neuropsychopharmacology, Saint Germain en Laye, France
- Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal, (UMR 6602), Clermont-Ferrand, France
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7
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Kriner P, Brieger P, Pogarell O, Schüle C, Mußmann L, Korbmacher J, Seemüller F. Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project. Front Psychiatry 2024; 15:1425549. [PMID: 39015883 PMCID: PMC11250482 DOI: 10.3389/fpsyt.2024.1425549] [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: 04/30/2024] [Accepted: 06/07/2024] [Indexed: 07/18/2024] Open
Abstract
Objectives Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. Methods We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Results Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Conclusion Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials should be conducted in the future to prospectively investigate different implementation strategies.
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Affiliation(s)
- Paul Kriner
- Department of Psychiatry and Psychotherapy, kbo-Lech-Mangfall-Klinik Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany
| | - Peter Brieger
- Department of Psychiatry and Psychotherapy, kbo-Isar-Amper-Klinikum, Haar, Germany
| | - Oliver Pogarell
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
| | - Cornelius Schüle
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
| | - Lisa Mußmann
- Bavarian Institute for Data, Analysis and Quality Assurance, Munich, Germany
| | - Julie Korbmacher
- Bavarian Institute for Data, Analysis and Quality Assurance, Munich, Germany
| | - Florian Seemüller
- Department of Psychiatry and Psychotherapy, kbo-Lech-Mangfall-Klinik Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
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8
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Bortolozzi A, Fico G, Berk M, Solmi M, Fornaro M, Quevedo J, Zarate CA, Kessing LV, Vieta E, Carvalho AF. New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview. Pharmacol Rev 2024; 76:323-357. [PMID: 38697859 PMCID: PMC11068842 DOI: 10.1124/pharmrev.120.000007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 05/05/2024] Open
Abstract
Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.
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Affiliation(s)
- Analia Bortolozzi
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Giovanna Fico
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Michael Berk
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Marco Solmi
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Michele Fornaro
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Joao Quevedo
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Carlos A Zarate
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Lars V Kessing
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Eduard Vieta
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
| | - Andre F Carvalho
- Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona, Spain (A.B.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.B., G.F., E.V.); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain (A.B., G.F., E.V.); Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain (G.F., E.V.); IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia (M.B., A.F.C.); Department of Psychiatry, University of Ottawa, Ontario, Canada (M.S.); The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, Canada (M.S.); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany (M.S.); Section of Psychiatry, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University of Naples, Naples, Italy (M.F.); Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, Texas (J.Q.); Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.); Copenhagen Affective Disorders Research Centre (CADIC), Psychiatric Center Copenhagen, Rigshospitalet, Denmark (L.V.K.); and Department of Clinical Medicine, University of Copenhagen, Denmark (L.V.K.)
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9
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Korkmaz ŞA, Gürler S. Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study. Curr Med Res Opin 2024; 40:855-861. [PMID: 38557295 DOI: 10.1080/03007995.2024.2337685] [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: 01/18/2024] [Accepted: 03/28/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVE Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. METHODS The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. RESULTS Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. CONCLUSIONS In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.
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Affiliation(s)
| | - Sümeyye Gürler
- Department of Psychiatry, Ankara Bilkent City Hospital, Ankara, Turkey
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10
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Kessing LV, Christensen EM, Krarup SK, Kyster N, Pedersen L, Legind C, Hansen L, Vejstrup B, Faurholt-Jepsen M, Baandrup L, Knorr U. An algorithm for pharmacological treatment of mania during hospitalisation. DANISH MEDICAL JOURNAL 2024; 71:A08230525. [PMID: 38704837 DOI: 10.61409/a08230525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
Current evidence for pharmacological treatment of mania during hospitalisation is insufficient as there are no larger well-designed randomised trials of comparative medical treatments of mania during inpatient stays. Moreover, there is considerable variation in pharmacological medication in clinical practice during hospitalisation for mania. Based on a hospital data overview, a systematic search of the literature and a three-day consensus meeting, this narrative review proposed an algorithm for optimised pharmacological treatment of mania during hospitalisation and its subsequent scientific evaluation.
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Affiliation(s)
- Lars Vedel Kessing
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
- Department of Clinical Medicine, University of Copenhagen
| | | | - Sarah Krarup Krarup
- Psychiatric Center North Zealand, Mental Health Services, Capital Region of Denmark, Denmark
| | - Natacha Kyster
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
| | - Lykke Pedersen
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
| | - Christian Legind
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
- Department of Clinical Medicine, University of Copenhagen
| | - Line Hansen
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
| | - Birgitte Vejstrup
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
| | - Maria Faurholt-Jepsen
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
- Department of Clinical Medicine, University of Copenhagen
| | - Lone Baandrup
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
- Department of Clinical Medicine, University of Copenhagen
| | - Ulla Knorr
- Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark
- Department of Clinical Medicine, University of Copenhagen
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11
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Ardila CM, López-Valencia A, González-Arroyave D. Severe Sinus Dysfunction in the Context of Chronic Lithium Intoxication and Poorly Controlled Hypothyroidism. Cureus 2024; 16:e55127. [PMID: 38558727 PMCID: PMC10979516 DOI: 10.7759/cureus.55127] [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] [Accepted: 02/28/2024] [Indexed: 04/04/2024] Open
Abstract
Cardiotoxicity associated with lithium is not a common event; however, it is potentially life-threatening, manifesting electrocardiographically with sinoatrial blocks, high-degree atrioventricular blocks, QT prolongation, and ventricular tachyarrhythmias. This case report presents a patient with severe sinus dysfunction in a clinically severe presentation secondary to cardiogenic shock. The patient sought medical attention for a one-week history of non-anginal chest pain, dizziness without syncope, generalized weakness, and somnolence progressing to bedridden status in the days preceding hospital admission. Laboratory findings revealed elevated blood levels of lithium and thyroid-stimulating hormone (TSH), along with concomitant Acute Kidney Injury Network (AKIN) II acute kidney injury. Subsequently, the patient was admitted to the intensive care unit, where persistent extreme sinus bradycardia of 30 bpm (beats per minute) with sinus pauses without ischemic changes was observed. The patient received supportive treatment, including renal replacement therapy, resulting in complete recovery of hemodynamic status without the need for long-term cardiac conduction devices.
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12
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Cutler AJ, Laliberté F, Germain G, MacKnight SD, Boudreau J, Wade SW, Parikh M. Healthcare resource utilization and costs associated with first versus subsequent use of cariprazine for bipolar I disorder. J Med Econ 2024; 27:1472-1484. [PMID: 39531329 DOI: 10.1080/13696998.2024.2419721] [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: 03/15/2024] [Revised: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024]
Abstract
AIMS To evaluate the healthcare resource utilization (HRU) and costs of patients who initiated cariprazine as their first versus subsequent atypical antipsychotic (AA) following a bipolar I disorder (BP-I) diagnosis. METHODS Adults with a BP-I diagnosis (first claim = index), commercial, Medicare Supplemental, or Medicaid insurance, and ≥1 outpatient cariprazine dispensing were identified from Merative MarketScan database. Cohorts included patients who initiated cariprazine as either their first or subsequent AA after initial BP-I diagnosis. Characteristics were balanced between cohorts using inverse probability of treatment weighting (IPTW). Outcomes evaluated post-index included all-cause and mental health (MH)-related HRU (hospitalizations, emergency department [ED] visits, outpatient visits), total healthcare costs (medical + pharmacy), and treatment patterns. HRU and healthcare costs were reported per patient-year (PPY) and compared between cohorts using rate ratios and 95% CIs estimated using nonparametric bootstrap procedures. Treatment patterns were analyzed descriptively, with standardized differences ≥10% considered important. RESULTS After IPTW, cohorts included 1,409 patients who initiated cariprazine first and 1,621 patients who initiated cariprazine subsequently; the average (standard deviation, SD) observation period was 678 (373) and 758 (389) days for first and subsequent initiators, respectively. Patients who initiated cariprazine first had 23% fewer all-cause hospitalizations and 28% fewer MH-related hospitalizations PPY (each comparison, p < 0.001). Rates of all-cause and MH-related outpatient visits were significantly lower in patients who initiated cariprazine first versus subsequently (each comparison, p < 0.001), while rates of ED visits were similar. Relative to subsequent initiators, first initiators incurred $2,587 and $2,130 lower all-cause and MH-related total healthcare costs PPY, respectively (each comparison, p < 0.05). Before starting cariprazine, first initiators used fewer BP-I-related medications on average than subsequent initiators (2.6 vs 3.9; standardized difference = 23.9%). LIMITATIONS Potential coding inaccuracies and residual confounding. CONCLUSIONS In this real-world database analysis, patients with BP-I who initiated cariprazine as their first AA had lower rates of HRU and incurred lower costs than patients who initiated cariprazine as a subsequent AA.
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Affiliation(s)
- Andrew J Cutler
- Department of Psychiatry, SUNY Upstate Medical University, Lakewood Ranch, FL, USA
| | | | | | | | | | - Sally W Wade
- Wade Outcomes Research and Consulting, Salt Lake City, UT, USA
| | - Mousam Parikh
- Health Economics and Outcomes Research, AbbVie, Florham Park, NJ, USA
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13
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Thomaidis GV, Papadimitriou K, Michos S, Chartampilas E, Tsamardinos I. A characteristic cerebellar biosignature for bipolar disorder, identified with fully automatic machine learning. IBRO Neurosci Rep 2023; 15:77-89. [PMID: 38025660 PMCID: PMC10668096 DOI: 10.1016/j.ibneur.2023.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 05/19/2023] [Accepted: 06/29/2023] [Indexed: 12/01/2023] Open
Abstract
Background Transcriptomic profile differences between patients with bipolar disorder and healthy controls can be identified using machine learning and can provide information about the potential role of the cerebellum in the pathogenesis of bipolar disorder.With this aim, user-friendly, fully automated machine learning algorithms can achieve extremely high classification scores and disease-related predictive biosignature identification, in short time frames and scaled down to small datasets. Method A fully automated machine learning platform, based on the most suitable algorithm selection and relevant set of hyper-parameter values, was applied on a preprocessed transcriptomics dataset, in order to produce a model for biosignature selection and to classify subjects into groups of patients and controls. The parent GEO datasets were originally produced from the cerebellar and parietal lobe tissue of deceased bipolar patients and healthy controls, using Affymetrix Human Gene 1.0 ST Array. Results Patients and controls were classified into two separate groups, with no close-to-the-boundary cases, and this classification was based on the cerebellar transcriptomic biosignature of 25 features (genes), with Area Under Curve 0.929 and Average Precision 0.955. The biosignature includes both genes connected before to bipolar disorder, depression, psychosis or epilepsy, as well as genes not linked before with any psychiatric disease. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed participation of 4 identified features in 6 pathways which have also been associated with bipolar disorder. Conclusion Automated machine learning (AutoML) managed to identify accurately 25 genes that can jointly - in a multivariate-fashion - separate bipolar patients from healthy controls with high predictive power. The discovered features lead to new biological insights. Machine Learning (ML) analysis considers the features in combination (in contrast to standard differential expression analysis), removing both irrelevant as well as redundant markers, and thus, focusing to biological interpretation.
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Affiliation(s)
- Georgios V. Thomaidis
- Greek National Health System, Psychiatric Department, Katerini General Hospital, Katerini, Greece
| | - Konstantinos Papadimitriou
- Greek National Health System, G. Papanikolaou General Hospital, Organizational Unit - Psychiatric Hospital of Thessaloniki, Thessaloniki, Greece
| | | | - Evangelos Chartampilas
- Laboratory of Radiology, AHEPA General Hospital, University of Thessaloniki, Thessaloniki, Greece
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14
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Greil W, de Bardeci M, Müller-Oerlinghausen B, Nievergelt N, Stassen H, Hasler G, Erfurth A, Cattapan K, Rüther E, Seifert J, Toto S, Bleich S, Schoretsanitis G. Controversies regarding lithium-associated weight gain: case-control study of real-world drug safety data. Int J Bipolar Disord 2023; 11:34. [PMID: 37840048 PMCID: PMC10577117 DOI: 10.1186/s40345-023-00313-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/27/2023] [Indexed: 10/17/2023] Open
Abstract
BACKGROUND The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). METHODS We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: "Arzneimittelsicherheit in der Psychiatrie"; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. RESULTS We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9-5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7-28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3-8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1-5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. CONCLUSIONS Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives.
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Affiliation(s)
- Waldemar Greil
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstr. 7, 80331, Munich, Germany.
- Psychiatric Private Hospital, Sanatorium Kilchberg, Zurich, Switzerland.
| | - Mateo de Bardeci
- Psychiatric Private Hospital, Sanatorium Kilchberg, Zurich, Switzerland
- Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland
| | - Bruno Müller-Oerlinghausen
- Charité Universitätsmedizin-Berlin, Berlin, Germany
- Medical Faculty Brandenburg Theodor Fontane, Neuruppin, Germany
- Drug Commission of the German Medical Association, Berlin, Germany
| | - Nadja Nievergelt
- Psychiatric Private Hospital, Sanatorium Kilchberg, Zurich, Switzerland
| | - Hans Stassen
- Psychiatric Private Hospital, Sanatorium Kilchberg, Zurich, Switzerland
- Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland
- IFMA Preventive Health Management Inc., 80 Pine Street, 24th Floor, New York, NY, 10005, USA
| | - Gregor Hasler
- Psychiatry Research Unit, University of Fribourg, Fribourg, Switzerland
| | - Andreas Erfurth
- Klinik Hietzing, 1st Department of Psychiatry and Psychotherapeutic Medicine, Vienna, Austria
| | - Katja Cattapan
- Psychiatric Private Hospital, Sanatorium Kilchberg, Zurich, Switzerland
- University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
| | - Eckart Rüther
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstr. 7, 80331, Munich, Germany
| | - Johanna Seifert
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Sermin Toto
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Stefan Bleich
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Georgios Schoretsanitis
- Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland
- The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA
- Department of Psychiatry at the Donald and Barbara Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA
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15
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Rohde C, Köhler-Forsberg O, Nierenberg AA, Østergaard SD. Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients. Bipolar Disord 2023; 25:323-334. [PMID: 36751986 DOI: 10.1111/bdi.13308] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
OBJECTIVE While treatment with antipsychotics and antiepileptics have been associated with an increased risk of diabetes mellitus (DM), lithium may have the opposite effect via inhibition of glycogen synthase kinase-3. The aim of this study was to investigate whether treatment of bipolar disorder with lithium, antipsychotics, or antiepileptics is associated with the risk of DM in a real-world clinical setting. METHODS Using nationwide registers, we identified all patients diagnosed with bipolar disorder in Danish Psychiatric Services from January 1, 1996, to January 1, 2019 (N = 30,451). The risk of developing DM was operationalized via hospital diagnoses and redeemed prescriptions for glucose-lowering drugs. For lithium, antipsychotics, valproate, and lamotrigine, we calculated hazard rate ratios (HRR) for developing DM via adjusted Cox proportional hazards models. Potential cumulative dose-response-like associations were examined using the log-rank test. RESULTS During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, we found no clinically or statistically significant difference in the risk of developing DM among patients receiving lithium (n = 11,690; incidence rate of DM/1000 person-years (IR) = 8.87, 95% CI: 8.02-9.90; HRR = 0.94, 95% CI: 0.84-1.06) or lamotrigine (n = 11,785; IR = 7.58, 95% CI: 6.69-8.59; HRR = 0.89, 95% CI: 0.77-1.02), respectively. Conversely, for patients receiving valproate (n = 5171; IR = 12.68, 95% CI: 10.87-14.80; HRR = 1.34, 95% CI: 1.14-1.58) and antipsychotics (n = 22,719; IR = 12.00, 95% CI: 11.14-12.94; HRR = 1.65, 95% CI: 1.45-1.88), respectively, there was increased risk of developing DM. For antipsychotics, we observed a clear cumulative dose-response-like association with the risk of DM. CONCLUSIONS Treatment with valproate and antipsychotics-but not with lithium and lamotrigine-was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder.
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Affiliation(s)
- Christopher Rohde
- Department of Affective Disorders, Aarhus University Hospital Psychiatry, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Ole Köhler-Forsberg
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
| | - Andrew A Nierenberg
- Department of Affective Disorders, Aarhus University Hospital Psychiatry, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Søren Dinesen Østergaard
- Department of Affective Disorders, Aarhus University Hospital Psychiatry, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Abstract
Bipolar disorders (BDs) are recurrent and sometimes chronic disorders of mood that affect around 2% of the world's population and encompass a spectrum between severe elevated and excitable mood states (mania) to the dysphoria, low energy, and despondency of depressive episodes. The illness commonly starts in young adults and is a leading cause of disability and premature mortality. The clinical manifestations of bipolar disorder can be markedly varied between and within individuals across their lifespan. Early diagnosis is challenging and misdiagnoses are frequent, potentially resulting in missed early intervention and increasing the risk of iatrogenic harm. Over 15 approved treatments exist for the various phases of bipolar disorder, but outcomes are often suboptimal owing to insufficient efficacy, side effects, or lack of availability. Lithium, the first approved treatment for bipolar disorder, continues to be the most effective drug overall, although full remission is only seen in a subset of patients. Newer atypical antipsychotics are increasingly being found to be effective in the treatment of bipolar depression; however, their long term tolerability and safety are uncertain. For many with bipolar disorder, combination therapy and adjunctive psychotherapy might be necessary to treat symptoms across different phases of illness. Several classes of medications exist for treating bipolar disorder but predicting which medication is likely to be most effective or tolerable is not yet possible. As pathophysiological insights into the causes of bipolar disorders are revealed, a new era of targeted treatments aimed at causal mechanisms, be they pharmacological or psychosocial, will hopefully be developed. For the time being, however, clinical judgment, shared decision making, and empirical follow-up remain essential elements of clinical care. This review provides an overview of the clinical features, diagnostic subtypes, and major treatment modalities available to treat people with bipolar disorder, highlighting recent advances and ongoing therapeutic challenges.
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Affiliation(s)
- Fernando S Goes
- Precision Medicine Center of Excellence in Mood Disorders, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
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17
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Seki T, Aki M, Furukawa TA, Kawashima H, Miki T, Sawaki Y, Ando T, Katsuragi K, Kawashima T, Ueno S, Miyagi T, Noma S, Tanaka S, Kawakami K. Electronic Health Record-Nested Reminders for Serum Lithium Level Monitoring in Patients With Mood Disorder: Randomized Controlled Trial. J Med Internet Res 2023; 25:e40595. [PMID: 36947138 PMCID: PMC10139684 DOI: 10.2196/40595] [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: 06/28/2022] [Revised: 01/12/2023] [Accepted: 02/21/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Clinical guidelines recommend regular serum lithium monitoring every 3 to 6 months. However, in the real world, only a minority of patients receive adequate monitoring. OBJECTIVE This study aims to examine whether the use of the electronic health record (EHR)-nested reminder system for serum lithium monitoring can help achieve serum lithium concentrations within the therapeutic range for patients on lithium maintenance therapy. METHODS We conducted an unblinded, single-center, EHR-nested, parallel-group, superiority randomized controlled trial comparing EHR-nested reminders with usual care in adult patients receiving lithium maintenance therapy for mood disorders. The primary outcome was the achievement of therapeutically appropriate serum lithium levels between 0.4 and 1.0 mEq/L at 18 months after enrollment. The key secondary outcomes are included as follows: the number of serum lithium level monitoring except for the first and final monitoring; exacerbation of the mood disorder during the study period, defined by hospitalization, increase in lithium dose, addition of antipsychotic drugs or mood stabilizers, or addition or increase of antidepressants; adherence defined by the proportion of days covered by lithium carbonate prescription during the study period. RESULTS A total of 111 patients were enrolled in this study. A total of 56 patients were assigned to the reminder group, and 55 patients were assigned to the usual care group. At the follow-up, 38 (69.1%) patients in the reminder group and 33 (60.0%) patients in the usual care group achieved the primary outcome (odds ratio 2.14, 95% CI 0.82-5.58, P=.12). The median number of serum lithium monitoring was 2 in the reminder group and 0 in the usual care group (rate ratio 3.62; 95% CI 2.47-5.29, P<.001). The exacerbation of mood disorders occurred in 17 (31.5%) patients in the reminder group and in 16 (34.8%) patients in the usual care group (odds ratio 0.97, 95% CI 0.42-2.28, P=.95). CONCLUSIONS We found insufficient evidence for an EHR-nested reminder to increase the achievement of therapeutic serum lithium concentrations. However, the number of monitoring increased with relatively simple and inexpensive intervention. The EHR-based reminders may be useful to improve quality of care for patients on lithium maintenance therapy, and they have potentials to be applied to other problems. TRIAL REGISTRATION University Hospital Medical Information Network Clinical Trials Registry UMIN000033633; https://tinyurl.com/5n7wtyav.
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Affiliation(s)
- Tomotsugu Seki
- Department of Pharmacoepidemiology, School of Public Health, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Morio Aki
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Toshi A Furukawa
- Department of Health Promotion and Human Behavior, School of Public Health, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hirotsugu Kawashima
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Tomotaka Miki
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Yujin Sawaki
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
- National Epilepsy Center, National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
| | - Takaaki Ando
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Kentaro Katsuragi
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Takahiko Kawashima
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Senkei Ueno
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
| | - Takashi Miyagi
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
- Department of Psychiatry, Kyoto-Katsura Hospital, Kyoto, Japan
| | - Shun'ichi Noma
- Department of Psychiatry, Toyooka Hospital, Toyooka, Japan
- Department of Psychiatry, Kyoto University Hospital, Kyoto, Japan
- Noma-Kokoro Clinic, Kyoto, Japan
| | - Shiro Tanaka
- Department of Clinical Biostatistics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koji Kawakami
- Department of Pharmacoepidemiology, School of Public Health, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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18
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Stefana A, Fusar-Poli P, D’Imperio D, Choplin EG, Dakanalis A, Vieta E, Youngstrom EA. Mapping the psychoanalytic literature on bipolar disorder: a scoping review of journal articles. REVISTA BRASILEIRA DE PSIQUIATRIA (SAO PAULO, BRAZIL : 1999) 2023; 45:71-83. [PMID: 36331980 PMCID: PMC9976923 DOI: 10.47626/1516-4446-2022-2765] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 09/12/2022] [Indexed: 11/05/2022]
Abstract
OBJECTIVE To provide a review of journal articles discussing clinical cases or vignettes of psychoanalysis or psychoanalytic psychotherapy of patients affected by bipolar disorder. METHODS A thorough search of journal articles was performed in five databases to identify studies published from 1990-2021. RESULTS Twenty-four articles were included in this review, comprising a total of 29 case reports. The most common theoretical approach adopted by the authors was "object relations." Two main sets of clinical-theoretical considerations and recommendations emerge: the applicability of analytic treatment to patients with bipolar disorder - taking into account their analyzability and practical arrangements for conducting therapy - and theoretical speculations on the nature and development of the illness, as well as on the conceptualization of its different phases. CONCLUSION Our findings reveal that there is some psychoanalytic literature providing insight into the psychological dynamics and treatment of patients with bipolar disorder. Elaboration of this literature may help improve our understanding and provide more accurate and comprehensive descriptions of the intrapsychic and interpersonal dynamics of these patients, yielding potentially valuable information for clinical and research purposes, particularly with regard to reducing interpersonal conflict, and increasing insight and engagement with lifestyle changes and other behaviors likely to promote health and stability.
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Affiliation(s)
- Alberto Stefana
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Paolo Fusar-Poli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK
- Early Psychosis: Interventions and Clinical-Detection Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Daniela D’Imperio
- Scientific Institute for Research, Hospitalization and Healthcare San Camillo Hospital, Venice, Italy
| | - Emma G. Choplin
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Antonios Dakanalis
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center for Mental Health Network, University of Barcelona, Barcelona, Catalonia, Spain
| | - Eric A. Youngstrom
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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19
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Chen PH, Tsai SY, Chen PY, Pan CH, Su SS, Chen CC, Kuo CJ. Mood stabilizers and risk of all-cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study. Acta Psychiatr Scand 2023; 147:234-247. [PMID: 36367926 DOI: 10.1111/acps.13519] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVES People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all-cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. METHODS In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time-dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. RESULTS The SMRs of all-cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all-cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5-year follow-up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all-cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001). CONCLUSION In addition to having protective effects against suicide and all-cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality.
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Affiliation(s)
- Pao-Huan Chen
- Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan.,Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shang-Ying Tsai
- Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan.,Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Po-Yu Chen
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
| | - Chun-Hung Pan
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.,Department of Psychology, National Chengchi University, Taipei, Taiwan
| | - Sheng-Siang Su
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
| | - Chiao-Chicy Chen
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan.,Department of Psychiatry, Mackay Medical College, Taipei, Taiwan
| | - Chian-Jue Kuo
- Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
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20
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Jeong JH, Bahk WM, Woo YS, Yoon BH, Lee JG, Kim W, Sohn I, Park SY, Shim SH, Seo JS, Choo ILH, Yang CM, Jung MH, Jon DI, Kim MD. Korean Medication Algorithm Project for Bipolar Disorder 2022: Comparisons with Other Treatment Guidelines. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2023; 21:32-48. [PMID: 36700310 PMCID: PMC9889890 DOI: 10.9758/cpn.2023.21.1.32] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 01/27/2023]
Abstract
The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.
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Affiliation(s)
- Jong-Hyun Jeong
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Psychiatry, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Won-Myong Bahk
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Sup Woo
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Bo-Hyun Yoon
- Department of Psychiatry, Naju National Hospital, Naju, Korea
| | - Jung Goo Lee
- Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Korea
| | - Won Kim
- Department of Psychiatry, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea
| | - InKi Sohn
- Department of Psychiatry, Keyo Hospital, Uiwang, Korea
| | | | - Se-Hoon Shim
- Department of Psychiatry, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Jeong Seok Seo
- Department of Psychiatry, Chung-Ang University College of Medicine, Seoul, Korea
| | - IL Han Choo
- Department of Psychiatry, College of Medicine, Chosun University, Gwangju, Korea
| | - Chan-Mo Yang
- Department of Psychiatry, Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan, Korea
| | - Myung Hun Jung
- Department of Psychiatry, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Korea
| | - Duk-In Jon
- Department of Psychiatry, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Korea
| | - Moon-Doo Kim
- Department of Psychiatry, Jeju National University Hospital, Jeju, Korea
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21
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Goulding EH, Dopke CA, Rossom R, Jonathan G, Mohr D, Kwasny MJ. Effects of a Smartphone-Based Self-management Intervention for Individuals With Bipolar Disorder on Relapse, Symptom Burden, and Quality of Life: A Randomized Clinical Trial. JAMA Psychiatry 2023; 80:109-118. [PMID: 36542401 PMCID: PMC9857325 DOI: 10.1001/jamapsychiatry.2022.4304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 10/25/2022] [Indexed: 12/24/2022]
Abstract
Importance Bipolar disorder-specific psychotherapy combined with pharmacotherapy improves relapse risk, symptom burden, and quality of life, but psychotherapy is not easily accessible. Objective To determine if a smartphone-based self-management intervention (LiveWell) can assist individuals with bipolar disorder to maintain wellness. Design, Setting, and Participants An assessor-blind randomized clinical trial enrolled participants from March 20, 2017, to April 25, 2019, with 48-week follow-up ending on April 10, 2020. Participants were randomly assigned to usual care or usual care plus the smartphone intervention stratified by relapse risk based on initial clinical status (low risk: asymptomatic recovery; high risk: continued symptomatic, prodromal, recovering, symptomatic recovery). Participants with bipolar disorder I were recruited from clinics in the Chicago and Minneapolis-Saint Paul areas. Data were analyzed from June 19, 2020, to May 25, 2022. Interventions The smartphone-based self-management intervention consisted of an application (app), coach, and website. Over 16 weeks, participants had a coach visit followed by 6 phone calls, and they completed daily and weekly app check-ins. The app provided adaptive feedback and information for developing a personalized wellness plan, the coach provided support, and the website provided summary data and alerts. Main Outcomes and Measures The primary outcome was time to relapse. Secondary outcomes were percentage-time symptomatic, symptom severity, and quality of life. Results Of the 205 randomized participants (mean [SD] age, 42 [12] years; 125 female individuals [61%]; 5 Asian [2%], 21 Black [10%], 13 Hispanic or Latino [6%], 7 multiracial [3%], 170 White [83%], 2 unknown race [1%]), 81 (40%) were randomly assigned to usual care, and 124 (60%) were randomly assigned to usual care plus the smartphone intervention. This clinical trial did not detect a reduction in relapse risk for the smartphone intervention (hazard ratio [HR], 0.65; 95% CI, 0.39-1.09; log-rank P = .08). However, decreased relapse was observed for low-risk individuals (HR, 0.32; 95% CI, 0.12-0.88; log-rank P = .02) but not high-risk individuals (HR, 0.86; 95% CI, 0.47-1.57; log-rank P = .62). Reduced manic symptom severity was observed for low-risk individuals (mean [SE] difference, -1.4 [0.4]; P = .001) but not for high-risk individuals (mean [SE] difference, 0 [0.3]; P = .95). The smartphone-based self-management intervention decreased depressive symptom severity (mean [SE] difference, -0.80 [0.34]; P = .02) and improved relational quality of life (mean [SE] difference, 1.03 [0.45]; P = .02) but did not decrease percentage-time symptomatic (mean [SE] difference, -5.6 [4.3]; P = .20). Conclusions and Relevance This randomized clinical trial of a smartphone-based self-management intervention did not detect a significant improvement in the primary outcome of time to relapse. However, a significant decrease in relapse risk was observed for individuals in asymptomatic recovery. In addition, the intervention decreased depressive symptom severity and improved relational quality of life. These findings warrant further work to optimize the smartphone intervention and confirm that the intervention decreases relapse risk for individuals in asymptomatic recovery. Trial Registration ClinicalTrials.gov Identifier: NCT03088462.
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Affiliation(s)
- Evan H. Goulding
- Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | - Cynthia A. Dopke
- Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | | | - Geneva Jonathan
- Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | - David Mohr
- Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | - Mary J. Kwasny
- Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
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22
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Mansur RB. Antidepressants in Bipolar Depression: Still Controversial After All These Years. Psychiatr Ann 2023. [DOI: 10.3928/00485713-20230119-02] [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: 02/17/2023]
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23
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Woo YS, Bahk WM, Jeong JH, Lee JG, Kim W, Sohn I, Park SY, Shim SH, Seo JS, Choo ILH, Yang CM, Jung MH, Jon DI, Kim MD, Yoon BH. Korean Medication Algorithm Project for Bipolar Disorder 2022, Fifth Revision: An Executive Summary. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2022; 20:747-761. [PMID: 36263649 PMCID: PMC9606436 DOI: 10.9758/cpn.2022.20.4.747] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 08/30/2023]
Abstract
OBJECTIVE We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder. METHODS The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts. RESULTS For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state. CONCLUSION The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.
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Affiliation(s)
- Young Sup Woo
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Won-Myong Bahk
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong-Hyun Jeong
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung Goo Lee
- Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Korea
| | - Won Kim
- Department of Psychiatry, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea
| | - InKi Sohn
- Department of Psychiatry, Keyo Hospital, Uiwang, Korea
| | | | - Se-Hoon Shim
- Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Korea
| | - Jeong Seok Seo
- Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul, Korea
| | - IL Han Choo
- Department of Psychiatry, College of Medicine, Chosun University, Gwangju, Korea
| | - Chan-Mo Yang
- Department of Psychiatry, Wonkwang University Hospital, School of Medicine, Wonkwang University, Iksan, Korea
| | - Myung Hun Jung
- Department of Psychiatry, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Duk-In Jon
- Department of Psychiatry, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Moon-Doo Kim
- Department of Psychiatry, Jeju National University Hospital, Jeju, Korea
| | - Bo-Hyun Yoon
- Department of Psychiatry, Naju National Hospital, Naju, Korea
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24
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Maruki T, Utsumi T, Takeshima M, Fujiwara Y, Matsui M, Aoki Y, Toda H, Watanabe N, Watanabe K, Takaesu Y. Efficacy and safety of adjunctive therapy to lamotrigine, lithium, or valproate monotherapy in bipolar depression: a systematic review and meta-analysis of randomized controlled trials. Int J Bipolar Disord 2022; 10:24. [PMID: 36269465 DOI: 10.1186/s40345-022-00271-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 09/16/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The efficacy and safety of adjunctive therapy are unclear in bipolar depression. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of second-generation antipsychotic, lamotrigine, lithium, or valproate therapy used in adjunction with lamotrigine, lithium, or valproate monotherapy in bipolar depression. A literature search of major electronic databases was conducted in February 2021, and all articles published until then were eligible. Two researchers independently screened relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. RESULTS Five studies met the inclusion criteria. The meta-analysis revealed significant differences in the following outcomes: (i) remission rates from depressive episodes (risk ratio [RR]: 1.23, 95% confidence interval [CI] 1.01-1.50, p = 0.04), (ii) improvement in depressive symptoms (standardized mean difference [SMD]: 0.21, 95% CI 0.09-0.34, p = 0.001), (iii) improvement in quality of life (SMD: 0.22, 95% CI 0.06-0.37, p = 0.005), and (iv) rate of adverse events during the study period (RR: 1.12, 95% CI 1.03-1.22, p = 0.008). There was no significant difference between adjunctive therapy and monotherapy in the emergence of suicide-related behaviors, dropout rate during the study period, or rate of manic switching. CONCLUSIONS Our results suggest that adjunctive second-generation antipsychotics, lamotrigine, lithium, or valproate increase both the benefits and risks in patients with bipolar depression, although there is no significant difference in severe adverse events. Adjunctive therapy should be provided through shared decision-making while considering the patients' condition in clinical settings.
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Affiliation(s)
- Taku Maruki
- Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan
| | - Tomohiro Utsumi
- Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan
| | - Masahiro Takeshima
- Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan
| | - Yu Fujiwara
- Department of Psychiatry, School of Medicine, National Defense Medical College, Saitama, Japan
| | - Marie Matsui
- Department of Psychiatry, School of Medicine, National Defense Medical College, Saitama, Japan
| | - Yumi Aoki
- Psychiatric & Mental Health Nursing, Graduate School of Nursing Science, St. Luke's International University, Tokyo, Japan
| | - Hiroyuki Toda
- Department of Psychiatry, School of Medicine, National Defense Medical College, Saitama, Japan
| | - Norio Watanabe
- Department of Psychiatry, Soseikai General Hospital, Kyoto, Japan
| | - Koichiro Watanabe
- Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan
| | - Yoshikazu Takaesu
- Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan. .,Department of Neuropsychiatry, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.
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25
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Piras M, Perra A, Gureje O, Preti A, Carta MG. The Current Quality of Web-Based Information on the Treatment of Bipolar Disorder: A Systematic Search. J Clin Med 2022; 11:jcm11185427. [PMID: 36143075 PMCID: PMC9501527 DOI: 10.3390/jcm11185427] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/21/2022] Open
Abstract
Background: An important aspect of managing chronic disorders like bipolar disorder is to have access to relevant health information. This study investigates and compares the quality of information on the treatments of bipolar disorder that is available on English websites, as an international language, and on Italian websites, as a popular local language. Methods: A systematic review search was obtained from four search engines. We excluded unrelated materials, scientific papers, and duplicates. We analyzed popularity with PageRank; technological quality with Nibbler; readability with the Flesh Reading Ease test and Gulpease index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and on the extent of adherence to the HONCode. Results: 35 English and 31 Italian websites were included. The English websites were found to have a higher level of quality information and technological quality than the Italian ones. Overall, the websites were found to be difficult to read, requiring a high level of education. Conclusions: These results can be important to inform guidelines for the improvement of health information and help users to reach a higher level of evidence on the websites. Users should find the benefits of treatment, support for shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing treatment.
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Affiliation(s)
- Martina Piras
- Innovation Sciences and Technologies, University of Cagliari, 09124 Cagliari, Italy
- Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
| | - Alessandra Perra
- Innovation Sciences and Technologies, University of Cagliari, 09124 Cagliari, Italy
- Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
- Correspondence: ; Tel.: +39-348-144-4501
| | - Oye Gureje
- Department of Psychiatry, University College Hospital, Ibadan 200285, Nigeria
| | - Antonio Preti
- Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Mauro Giovanni Carta
- Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
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26
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Adu MK, Eboreime E, Sapara AO, Agyapong VIO. The Use of Repetitive Transcranial Magnetic Stimulations for the Treatment of Bipolar Disorder: A Scoping Review. Behav Sci (Basel) 2022; 12:263. [PMID: 36004834 PMCID: PMC9404915 DOI: 10.3390/bs12080263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/14/2022] [Accepted: 07/27/2022] [Indexed: 12/02/2022] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that involves the application of magnetic pulses on hyperactive or hypoactive cortical brain areas. rTMS is considered a high therapeutic tool in many neuropsychiatric conditions. Despite its wide and continuous usage for the treatment of psychiatric disorders, information about the use of rTMS in bipolar disorders is limited and not well-established in the literature. Objectives: This scoping review aims to explore the literature available regarding the application of rTMS for the management of bipolar disorders, to garner evidence in support of it uses in the management of bipolar disorders, and for recommendations on future clinical and research work. Method: We electronically conducted a data search in five research databases (MEDLINE, CINAHL, Psych INFO, SCOPUS, and EMBASE) using all identified keywords across all the databases to identify evidence-based studies. Articles were included if they were published randomized control designs aimed at the use of rTMS in the management of bipolar disorders. Overall, nine studies were eligible for this review. The search results are up to date as of the final date of data search-20 December 2020. Only full-text published articles written in English were reviewed. Review articles on treatment with rTMS for conditions either than bipolar disorders were excluded. Conclusion: The application of rTMS intervention for bipolar disorders looks promising despite the diversity of its outcomes and its clinical significance. However, to be able to draw a definite conclusion on the clinical effectiveness of the technique, more randomized controlled studies with well-defined stimulation parameters need to be conducted with large sample sizes in the future.
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Affiliation(s)
- Medard Kofi Adu
- Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada; (E.E.); (A.O.S.); (V.I.O.A.)
| | - Ejemai Eboreime
- Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada; (E.E.); (A.O.S.); (V.I.O.A.)
| | - Adegboyega Oyekunbi Sapara
- Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada; (E.E.); (A.O.S.); (V.I.O.A.)
| | - Vincent Israel Opoku Agyapong
- Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada; (E.E.); (A.O.S.); (V.I.O.A.)
- Department of Psychiatry, Dalhousie University, Halifax, NS B3H 2E2, Canada
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27
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Real-World Long-Term Experience on Endoxifen in Bipolar Disorder with Psychotic Symptoms. Case Rep Psychiatry 2022; 2022:3684181. [PMID: 35818415 PMCID: PMC9271003 DOI: 10.1155/2022/3684181] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 11/29/2022] Open
Abstract
Evidence suggests that inhibition of protein kinase C (PKC) signalling may have a contributing role in the treatment of bipolar affective disorder (BPAD). Endoxifen, an active metabolite of tamoxifen, is a potent direct PKC inhibitor. This report presents a severe case of a BPAD patient with a baseline Young Mania Rating Scale (YMRS) score of 49, associated family history and addiction to psychostimulants, with no improvement by the first and second-generation antipsychotics. Treatment with endoxifen 8 mg once a day showed improvement in manic symptoms with a YMRS score of 4 and a reduction in the use of psychostimulants as well as other antipsychotic concomitant medications. No adverse effects were noted up to 8-month follow-up. Long-term treatment with endoxifen is safe and effective in severe BPAD.
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28
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Abstract
Bipolar disorder (BD) affects approximately 2% of U.S. adults and is the most costly mental health condition for commercial insurers nationwide. Rates of BD are elevated among persons with depression, anxiety disorders, and substance use disorders-conditions frequently seen by primary care clinicians. In addition, antidepressants can precipitate manic or hypomanic symptoms or rapid cycling in persons with undiagnosed BD. Thus, screening in these high-risk groups is indicated. Effective treatments exist, and many can be safely and effectively administered by primary care clinicians.
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Affiliation(s)
- Mark S Bauer
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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29
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Park JH, Nuñez NA, Gardea-Resendez M, Gerberi DJ, Breitinger S, Veldic M, Frye MA, Singh B. Short Term Second-Generation Antidepressant Monotherapy in Acute Depressive Episodes of Bipolar II Disorder: A Systematic Review and Meta-Analysis. PSYCHOPHARMACOLOGY BULLETIN 2022; 52:45-72. [PMID: 35721812 PMCID: PMC9172552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Purpose Bipolar II disorder (BD-II) has limited evidence-based treatment guidelines. The aim of this systematic review and meta-analysis was to estimate the efficacy and safety of second-generation antidepressant (SGAD) monotherapy in acute BD-II depression. Methods A literature search was conducted from the database inception through March 2021. Only randomized controlled trials (RCTs) were included. Outcome measures included: response rates, treatment-emergent affective switch (TEAS) rates, discontinuation due to side-effects, and all-cause discontinuation. Risk ratio (RR) was calculated using the Mantel-Haenszel random effects model. Results 3301 studies were screened, and 15 articles were selected for full-text review. Five studies met the inclusion criteria: Four double-blind RCTs (n = 533) and one open-label RCT (n = 83) were included. Two double-blind RCTs [n = 223, SGAD = 110 (venlafaxine = 65, sertraline = 45), lithium/control = 113] were included for meta-analysis. The response rate for SGAD monotherapy compared to lithium monotherapy were similar (RR = 1.44, 95% CI 0.78, 2.66). The TEAS rate for SGAD monotherapy was not significantly different from lithium monotherapy (p = 0.76). The discontinuation rate due to side-effects for SGAD monotherapy was significantly lower than lithium monotherapy with a RR = 0.32, 95% CI 0.11, 0.96, p = 0.04 but all-cause discontinuation rates were similar in both groups. Conclusions Limited data suggests short-term efficacy of venlafaxine and sertraline monotherapy in patients with acute BD-II depression with good side effect tolerability and without significantly increased switch rate. There is an urgent need for RCTs investigating the role of SGAD monotherapy in short and long-term among patients with BD-II.
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Affiliation(s)
- Jin Hong Park
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Nicolas A Nuñez
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Manuel Gardea-Resendez
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Danielle J Gerberi
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Scott Breitinger
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Marin Veldic
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Mark A Frye
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Balwinder Singh
- Park, M.D., Nuñez, M.D., Gardea-Resendez, M.D., Breitinger, M.D., Veldic, M.D. Frye, M.D. Singh, M.D., Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. Gerberi, M.L.S., Mayo Clinic Libraries, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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30
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Cheng C, Bai J. Association Between Polypharmacy, Anxiety, and Depression Among Chinese Older Adults: Evidence from the Chinese Longitudinal Healthy Longevity Survey. Clin Interv Aging 2022; 17:235-244. [PMID: 35283629 PMCID: PMC8909463 DOI: 10.2147/cia.s351731] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 02/28/2022] [Indexed: 12/16/2022] Open
Abstract
Purpose To investigate the association between polypharmacy, anxiety, and depression among Chinese older adults. Patients and Methods The data used in this study were from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the 2018 wave. Polypharmacy status was measured by the accumulation of self-reported medications. Anxiety and depression were assessed by the Generalized Anxiety Disorder (GAD-7) scale and the Center for Epidemiologic Studies Depression Scale (CES-D-10), respectively. Logistic regression models were performed. Results A total of 2484 Chinese older adults (female: 1321, 53.2%) aged from 60 to 117 years old were included in the analysis. Regression analysis showed that polypharmacy was associated with depression after controlling for the covariates. No association was observed between polypharmacy and anxiety. Conclusion There was a suggestive link between polypharmacy and depression among Chinese older adults. Having polypharmacy might be an indicator for the possible depression among this population, but a comprehensive assessment of polypharmacy is necessary.
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Affiliation(s)
- Cheng Cheng
- School of Nursing, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China
- Correspondence: Cheng Cheng, Tel/Fax +86-21-64431003, Email
| | - Jie Bai
- Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
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31
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Lin SK, Yang SY, Park SC, Jang OJ, Zhu X, Xiang YT, Ouyang WC, Javed A, Khan MNS, Grover S, Avasthi A, Kallivayalil RA, Chee KY, Chemi N, Kato TA, Hayakawa K, Pariwatcharakul P, Maramis M, Seneviratne L, Kang S, Tang WK, Oo T, Sartorius N, Tan CH, Chong MY, Park YC, Shinfuku N. Prescription Patterns for Bipolar Disorder in Asian Countries: Findings from Research on Asian Prescription Pattern-Bipolar Disorder. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2022; 20:61-69. [PMID: 35078949 PMCID: PMC8813322 DOI: 10.9758/cpn.2022.20.1.61] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 12/25/2020] [Accepted: 12/26/2020] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed. METHODS The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method. RESULTS Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries. CONCLUSION Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.
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Affiliation(s)
- Shih-Ku Lin
- Department of Psychiatry, Taipei City Hospital and Psychiatric Center, Taipei, Taiwan
- Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Shu-Yu Yang
- Department of Pharmacy, Taipei City Hospital, Taipei, Taiwan
| | - Seon-Cheol Park
- Department of Neuropsychiatry, Hanyang University Guri Hospital, Guri, Korea
| | - Ok-Jin Jang
- Department of Psychiatry, Bugok National Hospital, Changyeong, Korea
| | - Xiaomin Zhu
- Department of Psychiatry, Suzhou Guangji Hospital, the Affiliated Guangji Hospital of Soochow University, Suzhou, China
| | - Yu-Tao Xiang
- Department of Psychiatry, Beijing Anding Hospital of Capital Medical University, Beijing, China
- Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China
| | - Wen-Chen Ouyang
- Department of Geriatric Psychiatry, Jianan Psychiatric Center, Tainan, Taiwan
- Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
| | - Afzal Javed
- Pakistan Psychiatric Research Centre, Fountain House, Lahore, Pakistan
| | | | - Sandeep Grover
- Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajit Avasthi
- Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Kok Yoon Chee
- Department of Psychiatry & Mental Health, Tunku Abdul Rahman Institute of Neurosciences, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
| | - Norliza Chemi
- Department of Psychiatry and Mental Health, Hospital Kajang, Selangor, Malaysia
| | - Takahiro A. Kato
- Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kohei Hayakawa
- Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | - Margarita Maramis
- Department of Psychiatry, Dr. Soetomo Hospital - Faculty of Medicine, Airlangga University, Surabaya, Indonesia
| | - Lakmi Seneviratne
- Department of Psychiatry, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
| | - Sim Kang
- Institute of Mental Health, Buangkok Green Medical Park, Singapore
| | - Wai Kwong Tang
- Department of Psychiatry, Chinese University of Hong Kong, Hong Kong, China
| | - Tin Oo
- Mental Health Hospital, Yangon University of Medicine, Yangon, Myanmar
| | - Norman Sartorius
- Association for the Improvement of Mental Health Programs, Geneva, Switzerland
| | - Chay-Hoon Tan
- Department of Pharmacology, National University of Singapore, Singapore
| | - Mian-Yoon Chong
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung & Chang Gung University School of Medicine, Linkou, Taiwan
| | - Yong Chon Park
- Department of Neuropsychiatry, Hanyang University Guri Hospital, Guri, Korea
| | - Naotaka Shinfuku
- School of Human Sciences, Seinan Gakuin University, Fukuoka, Japan
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Goulding EH, Dopke CA, Rossom RC, Michaels T, Martin CR, Ryan C, Jonathan G, McBride A, Babington P, Bernstein M, Bank A, Garborg CS, Dinh JM, Begale M, Kwasny MJ, Mohr DC. A Smartphone-Based Self-management Intervention for Individuals With Bipolar Disorder (LiveWell): Empirical and Theoretical Framework, Intervention Design, and Study Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2022; 11:e30710. [PMID: 35188473 PMCID: PMC8902672 DOI: 10.2196/30710] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 11/27/2021] [Accepted: 11/30/2021] [Indexed: 12/18/2022] Open
Abstract
Background Bipolar disorder is a severe mental illness with high morbidity and mortality rates. Even with pharmacological treatment, frequent recurrence of episodes, long episode durations, and persistent interepisode symptoms are common and disruptive. Combining psychotherapy with pharmacotherapy improves outcomes; however, many individuals with bipolar disorder do not receive psychotherapy. Mental health technologies can increase access to self-management strategies derived from empirically supported bipolar disorder psychotherapies while also enhancing treatment by delivering real-time assessments, personalized feedback, and provider alerts. In addition, mental health technologies provide a platform for self-report, app use, and behavioral data collection to advance understanding of the longitudinal course of bipolar disorder, which can then be used to support ongoing improvement of treatment. Objective A description of the theoretical and empirically supported framework, design, and protocol for a randomized controlled trial (RCT) of LiveWell, a smartphone-based self-management intervention for individuals with bipolar disorder, is provided to facilitate the ability to replicate, improve, implement, and disseminate effective interventions for bipolar disorder. The goal of the trial is to determine the effectiveness of LiveWell for reducing relapse risk and symptom burden as well as improving quality of life (QOL) while simultaneously clarifying behavioral targets involved in staying well and better characterizing the course of bipolar disorder and treatment response. Methods The study is a single-blind RCT (n=205; 2:3 ratio of usual care vs usual care plus LiveWell). The primary outcome is the time to relapse. Secondary outcomes are percentage time symptomatic, symptom severity, and QOL. Longitudinal changes in target behaviors proposed to mediate the primary and secondary outcomes will also be determined, and their relationships with the outcomes will be assessed. A database of clinical status, symptom severity, real-time self-report, behavioral sensor, app use, and personalized content will be created to better predict treatment response and relapse risk. Results Recruitment and screening began in March 2017 and ended in April 2019. Follow-up ended in April 2020. The results of this study are expected to be published in 2022. Conclusions This study will examine whether LiveWell reduces relapse risk and symptom burden and improves QOL for individuals with bipolar disorder by increasing access to empirically supported self-management strategies. The role of selected target behaviors (medication adherence, sleep duration, routine, and management of signs and symptoms) in these outcomes will also be examined. Simultaneously, a database will be created to initiate the development of algorithms to personalize and improve treatment for bipolar disorder. In addition, we hope that this description of the theoretical and empirically supported framework, intervention design, and study protocol for the RCT of LiveWell will facilitate the ability to replicate, improve, implement, and disseminate effective interventions for bipolar and other mental health disorders. Trial Registration ClinicalTrials.gov NCT03088462; https://www.clinicaltrials.gov/ct2/show/NCT03088462 International Registered Report Identifier (IRRID) DERR1-10.2196/30710
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Affiliation(s)
- Evan H Goulding
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Cynthia A Dopke
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | | | - Tania Michaels
- Department of Psychiatry, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Clair R Martin
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Chloe Ryan
- Carolina Outreach, Durham, NC, United States
| | - Geneva Jonathan
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Alyssa McBride
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Pamela Babington
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Mary Bernstein
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Andrew Bank
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - C Spencer Garborg
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | | | | | - Mary J Kwasny
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - David C Mohr
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review. Cells 2022; 11:cells11040645. [PMID: 35203296 PMCID: PMC8869907 DOI: 10.3390/cells11040645] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/28/2022] [Accepted: 02/09/2022] [Indexed: 01/05/2023] Open
Abstract
Background and Objectives: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. Materials and Methods: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. Results: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. Conclusions: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine’s side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine–lamotrigine combination in bipolar patients.
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Madireddy S, Madireddy S. Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder. Int J Mol Sci 2022; 23:ijms23031844. [PMID: 35163764 PMCID: PMC8836876 DOI: 10.3390/ijms23031844] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/26/2021] [Accepted: 12/30/2021] [Indexed: 01/10/2023] Open
Abstract
Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.
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Affiliation(s)
- Sahithi Madireddy
- Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Correspondence:
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Natale A, Mineo L, Fusar-Poli L, Aguglia A, Rodolico A, Tusconi M, Amerio A, Serafini G, Amore M, Aguglia E. Mixed Depression: A Mini-Review to Guide Clinical Practice and Future Research Developments. Brain Sci 2022; 12:92. [PMID: 35053835 PMCID: PMC8773514 DOI: 10.3390/brainsci12010092] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 12/28/2022] Open
Abstract
The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.
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Affiliation(s)
- Antimo Natale
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (L.M.); (L.F.-P.); (A.R.); (E.A.)
| | - Ludovico Mineo
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (L.M.); (L.F.-P.); (A.R.); (E.A.)
| | - Laura Fusar-Poli
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (L.M.); (L.F.-P.); (A.R.); (E.A.)
| | - Andrea Aguglia
- Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16126 Genoa, Italy; (A.A.); (A.A.); (G.S.); (M.A.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Alessandro Rodolico
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (L.M.); (L.F.-P.); (A.R.); (E.A.)
| | - Massimo Tusconi
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy;
| | - Andrea Amerio
- Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16126 Genoa, Italy; (A.A.); (A.A.); (G.S.); (M.A.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Gianluca Serafini
- Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16126 Genoa, Italy; (A.A.); (A.A.); (G.S.); (M.A.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Mario Amore
- Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16126 Genoa, Italy; (A.A.); (A.A.); (G.S.); (M.A.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Eugenio Aguglia
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; (L.M.); (L.F.-P.); (A.R.); (E.A.)
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Malygin Y, Orlova A, Malygin V. Conceptualization of comorbid anxiety and depressive disorders and approaches to their managing. Zh Nevrol Psikhiatr Im S S Korsakova 2022; 122:48-54. [DOI: 10.17116/jnevro202212206148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Goulding EH, Dopke CA, Michaels T, Martin CR, Khiani MA, Garborg C, Karr C, Begale M. A Smartphone-Based Self-management Intervention for Individuals With Bipolar Disorder (LiveWell): Protocol Development for an Expert System to Provide Adaptive User Feedback. JMIR Form Res 2021; 5:e32932. [PMID: 34951598 PMCID: PMC8742209 DOI: 10.2196/32932] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 10/23/2021] [Accepted: 10/28/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Bipolar disorder is a severe mental illness that results in significant morbidity and mortality. While pharmacotherapy is the primary treatment, adjunctive psychotherapy can improve outcomes. However, access to therapy is limited. Smartphones and other technologies can increase access to therapeutic strategies that enhance self-management while simultaneously augmenting care by providing adaptive delivery of content to users as well as alerts to providers to facilitate clinical care communication. Unfortunately, while adaptive interventions are being developed and tested to improve care, information describing the components of adaptive interventions is often not published in sufficient detail to facilitate replication and improvement of these interventions. OBJECTIVE To contribute to and support the improvement and dissemination of technology-based mental health interventions, we provide a detailed description of the expert system for adaptively delivering content and facilitating clinical care communication for LiveWell, a smartphone-based self-management intervention for individuals with bipolar disorder. METHODS Information from empirically supported psychotherapies for bipolar disorder, health psychology behavior change theories, and chronic disease self-management models was combined with user-centered design data and psychiatrist feedback to guide the development of the expert system. RESULTS Decision points determining the timing of intervention option adaptation were selected to occur daily and weekly based on self-report data for medication adherence, sleep duration, routine, and wellness levels. These data were selected for use as the tailoring variables determining which intervention options to deliver when and to whom. Decision rules linking delivery of options and tailoring variable thresholds were developed based on existing literature regarding bipolar disorder clinical status and psychiatrist feedback. To address the need for treatment adaptation with varying clinical statuses, decision rules for a clinical status state machine were developed using self-reported wellness rating data. Clinical status from this state machine was incorporated into hierarchal decision tables that select content for delivery to users and alerts to providers. The majority of the adaptive content addresses sleep duration, medication adherence, managing signs and symptoms, building and utilizing support, and keeping a regular routine, as well as determinants underlying engagement in these target behaviors as follows: attitudes and perceptions, knowledge, support, evaluation, and planning. However, when problems with early warning signs, symptoms, and transitions to more acute clinical states are detected, the decision rules shift the adaptive content to focus on managing signs and symptoms, and engaging with psychiatric providers. CONCLUSIONS Adaptive mental health technologies have the potential to enhance the self-management of mental health disorders. The need for individuals with bipolar disorder to engage in the management of multiple target behaviors and to address changes in clinical status highlights the importance of detailed reporting of adaptive intervention components to allow replication and improvement of adaptive mental health technologies for complex mental health problems.
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Affiliation(s)
- Evan H Goulding
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Cynthia A Dopke
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Tania Michaels
- Deparment of Pediatrics, Loma Linda Children's Hospital, Loma Linda, CA, United States
| | - Clair R Martin
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | | | - Christopher Garborg
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Chris Karr
- Audacious Software, Chicago, IL, United States
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Hsu CW, Tsai SY, Wang LJ, Liang CS, Carvalho AF, Solmi M, Vieta E, Lin PY, Hu CA, Kao HY. Predicting Serum Levels of Lithium-Treated Patients: A Supervised Machine Learning Approach. Biomedicines 2021; 9:biomedicines9111558. [PMID: 34829787 PMCID: PMC8615637 DOI: 10.3390/biomedicines9111558] [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] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/23/2021] [Accepted: 10/25/2021] [Indexed: 11/16/2022] Open
Abstract
Routine monitoring of lithium levels is common clinical practice. This is because the lithium prediction strategies available developed by previous studies are still limited due to insufficient prediction performance. Thus, we used machine learning approaches to predict lithium concentration in a large real-world dataset. Real-world data from multicenter electronic medical records were used in different machine learning algorithms to predict: (1) whether the serum level was 0.6–1.2 mmol/L or 0.0–0.6 mmol/L (binary prediction), and (2) its concentration value (continuous prediction). We developed models from 1505 samples through 5-fold cross-validation and used 204 independent samples to test their performance by evaluating their accuracy. Moreover, we ranked the most important clinical features in different models and reconstructed three reduced models with fewer clinical features. For binary and continuous predictions, the average accuracy of these models was 0.70–0.73 and 0.68–0.75, respectively. Seven features were listed as important features related to serum lithium levels of 0.6–1.2 mmol/L or higher lithium concentration, namely older age, lower systolic blood pressure, higher daily and last doses of lithium prescription, concomitant psychotropic drugs with valproic acid and -pine drugs, and comorbid substance-related disorders. After reducing the features in the three new predictive models, the binary or continuous models still had an average accuracy of 0.67–0.74. Machine learning processes complex clinical data and provides a potential tool for predicting lithium concentration. This may help in clinical decision-making and reduce the frequency of serum level monitoring.
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Affiliation(s)
- Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (P.-Y.L.); (C.-A.H.)
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan 70101, Taiwan
- Correspondence: (C.-W.H.); (H.-Y.K.)
| | - Shang-Ying Tsai
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan;
- Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan
| | - Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;
| | - Chih-Sung Liang
- National Defense Medical Center, Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei 112003, Taiwan;
- National Defense Medical Center, Department of Psychiatry, Taipei 114201, Taiwan
| | - Andre F. Carvalho
- IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3216, Australia;
| | - Marco Solmi
- Psychiatry Department, University of Ottawa, Ottawa, ON K1N 6N5, Canada;
- The Ottawa Hospital, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON K1N 6N5, Canada
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, 08036 Barcelona, Catalonia, Spain;
| | - Pao-Yen Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (P.-Y.L.); (C.-A.H.)
- Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Chien-An Hu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (P.-Y.L.); (C.-A.H.)
| | - Hung-Yu Kao
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan 70101, Taiwan
- Correspondence: (C.-W.H.); (H.-Y.K.)
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Genetic variants associated with cardiometabolic abnormalities during treatment with selective serotonin reuptake inhibitors: a genome-wide association study. THE PHARMACOGENOMICS JOURNAL 2021; 21:574-585. [PMID: 33824429 DOI: 10.1038/s41397-021-00234-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 02/19/2021] [Accepted: 03/11/2021] [Indexed: 02/02/2023]
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are prescribed both to patients with schizophrenia and bipolar disorder. Previous studies have shown associations between SSRI treatment and cardiometabolic alterations. The aim of the present study was to investigate genetic variants associated with cardiometabolic adverse effects in patients treated with SSRIs in a naturalistic setting, using a genome-wide cross-sectional approach in a genetically homogeneous sample. We included and genotyped 1981 individuals with schizophrenia or bipolar disorder, of whom 1180 had information available on the outcomes low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, and body mass index (BMI) and investigated interactions between SNPs and SSRI use (N = 246) by conducting a genome-wide GxE analysis. We report 13 genome-wide significant interaction effects of SNPs and SSRI serum concentrations on LDL-cholesterol, HDL-cholesterol, and BMI, located in four distinct genomic loci. This study provides new insight into the pharmacogenetics of SSRI but warrants replication in independent populations.
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40
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ATAGÜN Mİ, ORAL T. Acute and Long Term Treatment of Manic Episodes in Bipolar Disorder. Noro Psikiyatr Ars 2021; 58:S24-S30. [PMID: 34658632 PMCID: PMC8498815 DOI: 10.29399/npa.27411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 05/26/2021] [Indexed: 11/20/2022] Open
Abstract
Bipolar disorder is a disabling psychiatric disorder which causes premature death and loss of quality of life. Despite the developments, novel treatments are partially effective and insufficient responses to treatment may cause loss of quality of life. Contemporary approaches to treatment planning involve taking the current symptoms and the personal treatment history of the patient into account and tailoring them for the treatment of each patient, i.e. individualized treatment. In this article, effects and side effects of antipsychotics, mood stabilizers and sedative hypnotic medications are reviewed and presented briefly for clinicians. Although novel developments have been observed in the literature about mixed states and psychotic symptoms, evidence-based options are still limited. Efficacy of mood stabilizers may be prolonged and additional medications may also be needed frequently in patients treated with mood stabilizers. Antipsychotics may cause several side effects and cannot be maintained for a long time in some of those patients. These factors may limit the use of mood stabilizers or antipsychotics. Therefore, the experience of the clinician and personal history of the patient still have importance in the procedure.
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Affiliation(s)
- Murat İlhan ATAGÜN
- Department of Psychiatry, İzmir Bakırçay University Faculty of Medicine, İzmir, Turkey
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Batmaz S, Altinoz AE, Sonkurt HO. Cognitive attentional syndrome and metacognitive beliefs as potential treatment targets for metacognitive therapy in bipolar disorder. World J Psychiatry 2021; 11:589-604. [PMID: 34631463 PMCID: PMC8474997 DOI: 10.5498/wjp.v11.i9.589] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 06/16/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Most treatment guidelines emphasize the use of psychotropic drugs for both the acute and maintenance treatment of bipolar disorder (BD). However, relying only on psychotropics without adjunctive psychosocial interventions may be insufficient in treating patients with BD. Given its unique view in the explanation of psychopathological states, metacognitive therapy (MCT) might be helpful for BD. Metacognitive theory posits that psychopathology is a result of the cognitive attentional syndrome (CAS) and that it is influenced and maintained by dysfunctional metacognitive beliefs, perseverative thinking, attentional biases, and dysfunctional coping strategies. In this review, literature data regarding these areas in BD are examined. Studies suggest that perseverative thinking might be among the emotion regulation strategies endorsed in individuals with BD. Regarding attentional biases, literature data show that state-dependent, mood-changing attentional biases and a ruminative self-focused attention are present. Studies also suggest that cognitive self-consciousness is higher in BD compared to controls. It is seen that maladaptive coping strategies are frequently reported in BD, and that these strategies are associated with depression severity, negative affect and relapse risk. Studies focusing on dysfunctional metacognitive beliefs in BD reported that individuals with BD had higher scores for negative metacognitive beliefs, self-consciousness, need to control thoughts, and a lack of cognitive confidence. Also, dysfunctional metacognitive beliefs were associated with depressive symptomatology. These findings suggest that the components of CAS and dysfunctional metacognitive beliefs are evident in BD. For a subgroup of patients with BD who fail to respond to evidence-based psychopharmacological and adjunctive psychotherapeutic interventions, MCT might be an alternative way to consider as a treatment option. In conclusion, taken the available data together, we propose a sequential treatment protocol for BD, mainly based on the MCT treatment plan of depressive disorders.
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Affiliation(s)
- Sedat Batmaz
- Department of Psychiatry, School of Medicine, Tokat Gaziosmanpasa University, Tokat 60100, Turkey
| | - Ali Ercan Altinoz
- Department of Psychiatry, School of Medicine, Eskisehir Osmangazi University, Eskisehir 26000, Turkey
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Sköld M, Rolstad S, Joas E, Kardell M, Pålsson E, Goodwin GM, Landén M. Regional lithium prescription rates and recurrence in bipolar disorder. Int J Bipolar Disord 2021; 9:18. [PMID: 34061259 PMCID: PMC8167923 DOI: 10.1186/s40345-021-00223-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 03/02/2021] [Indexed: 11/22/2022] Open
Abstract
Background Lithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes. Aims To estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden. Method Data from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately. Results Lithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately. Conclusions The advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium. Supplementary Information The online version contains supplementary material available at 10.1186/s40345-021-00223-7.
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Affiliation(s)
- Martin Sköld
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 15, 413 45, Gothenburg, Sweden
| | - Sindre Rolstad
- Department of Psychology, Faculty of Social Science, University of Gothenburg, Gothenburg, Sweden
| | - Erik Joas
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 15, 413 45, Gothenburg, Sweden
| | - Mathias Kardell
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 15, 413 45, Gothenburg, Sweden
| | - Erik Pålsson
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 15, 413 45, Gothenburg, Sweden
| | - Guy M Goodwin
- Department of Psychiatry, University of Oxford, Oxford, UK
| | - Mikael Landén
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 15, 413 45, Gothenburg, Sweden. .,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment. Int J Mol Sci 2021; 22:ijms22073723. [PMID: 33918462 PMCID: PMC8038247 DOI: 10.3390/ijms22073723] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 02/07/2023] Open
Abstract
The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut-brain-microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.
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Pérez de Mendiola X, Hidalgo-Mazzei D, Vieta E, González-Pinto A. Overview of lithium's use: a nationwide survey. Int J Bipolar Disord 2021; 9:10. [PMID: 33687600 PMCID: PMC7941362 DOI: 10.1186/s40345-020-00215-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 11/27/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Lithium is considered the gold standard treatment for bipolar disorder (BD). Current clinical guidelines and scientific evidence support its use as a first-line treatment in BD. However, over the last two decades, there has been a downward tendency in lithium's use in several developed countries. Based on a nationwide survey, this study's objective is to analyze in a large sample of psychiatrists relevant issues of the use of lithium salts in BD. METHODS Data were collected through an anonymous survey sent by email among 500 psychiatrists who belong to a National Society of Psychiatry (Spanish Society of Biological Psychiatry). The survey is a self-administered questionnaire consisting of 21 items on the most key aspects of lithium's use (indication, dosage, monitoring, and information for patients). RESULTS 212 psychiatrists completed the survey. 70% of psychiatrists prescribe lithium to more than 50% of patients diagnosed with BD. Adverse effects are the main reason not to use lithium salts. Over 75% of the participants consider lithium salts the treatment of choice for the maintenance phase of BD, both in women and men. Most of the participants (> 50%) start lithium after the first affective episode, use conservative plasma concentrations (0.6-0.8 mmol/L), and generally prescribe it twice a day. 57% of psychiatrists who treat patients under 18 do not use lithium in this population. About 70% of the survey respondents use official protocols to inform and monitor patients on lithium treatment. CONCLUSIONS From the results of the present study, it can be concluded that the use of lithium in Spain is in line with the recommendations of the main international clinical guidelines and current scientific literature. The first reason not to prescribe lithium in our country is the perception of its adverse effects and not the aspects related to its practical use or its effectiveness. Considering that BD is a chronic disease with a typical onset in adolescence, the low rate of prescription of lithium salts in patients under 18 must be thoroughly studied.
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Affiliation(s)
- Xabier Pérez de Mendiola
- Bioaraba, Research Group on Severe Mental Illness; Osakidetza, Araba University Hospital, Psychiatry Service; Faculty of Medicine, Department of Neurosciences, University of the Basque Country UPV / EHU, Vitoria-Gasteiz, Spain.
- Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, Centre for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona, Spain.
| | - Diego Hidalgo-Mazzei
- Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, Centre for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona, Spain
| | - Eduard Vieta
- Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, Centre for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona, Spain
| | - Ana González-Pinto
- Bioaraba, Research Group on Severe Mental Illness; Osakidetza, Araba University Hospital, Psychiatry Service; Faculty of Medicine, Department of Neurosciences, University of the Basque Country UPV / EHU, Vitoria-Gasteiz, Spain
- Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, Centre for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona, Spain
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Doane MJ, Ogden K, Bessonova L, O'Sullivan AK, Tohen M. Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review. Neuropsychiatr Dis Treat 2021; 17:515-531. [PMID: 33623386 PMCID: PMC7896797 DOI: 10.2147/ndt.s280051] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 01/06/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Treatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns. METHODS Structured, systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database identified primary research studies (published 2008-2018) describing real-world SGA use in adults with bipolar disorder/BD-I. RESULTS Among 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs. LIMITATIONS Different definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived. CONCLUSION Despite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.
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Affiliation(s)
- Michael J Doane
- Health Economics and Outcomes Research, Alkermes, Inc., Waltham, MA, USA
| | - Kristine Ogden
- Evidence, Worldwide Clinical Trials, Morrisville, NC, USA
| | - Leona Bessonova
- Health Economics and Outcomes Research, Alkermes, Inc., Waltham, MA, USA
| | - Amy K O'Sullivan
- Health Economics and Outcomes Research, Alkermes, Inc., Waltham, MA, USA
| | - Mauricio Tohen
- Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA
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Konno Y, Fujino Y, Ikenouchi A, Adachi N, Kubota Y, Azekawa T, Ueda H, Edagawa K, Katsumoto E, Goto E, Hongo S, Kato M, Tsuboi T, Yasui-Furukori N, Nakagawa A, Kikuchi T, Watanabe K, Yoshimura R. Relationship Between Mood Episode and Employment Status of Outpatients with Bipolar Disorder: Retrospective Cohort Study from the Multicenter Treatment Survey for Bipolar Disorder in Psychiatric Clinics (MUSUBI) Project. Neuropsychiatr Dis Treat 2021; 17:2867-2876. [PMID: 34522098 PMCID: PMC8434929 DOI: 10.2147/ndt.s322507] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/19/2021] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE The objective of this study was to clarify the relationship between mood episode and employment in patients with bipolar disorder to help improve their employment status. METHODS All medical records of patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics in September-October 2016 were investigated in September-October 2017. Details of the medical care received were investigated using a survey sheet, which included employment status. Odds ratios of mood episodes for employment status were analyzed using a logistic regression model. RESULTS Among patients aged 60 years or less, 2292 described their occupation. On univariate analysis, odds ratios were statistically significant for depressive episode (OR = 2.68 [1.50-4.78] p = 0.001) and manic episode (OR = 2.64 [1.07-6.47] p = 0.034), whereas no significant difference was noted for mixed episode (OR = 1.72 [0.69-4.33] p = 0.246). On multivariate analysis, odds ratios were statistically significant for depressive episode (OR = 2.16 [1.13-4.13], p = 0.020) and manic episode (OR = 3.55 [1.36-9.25], p = 0.010), whereas no significant difference was noted for mixed episode (OR = 1.83 [0.65-5.14] p = 0.254). CONCLUSION Employment status among these patients with bipolar disorder receiving outpatient treatment was 43.5%. Compared to remission episodes, manic and depressive episodes were associated with a higher risk of unemployment.
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Affiliation(s)
- Yusuke Konno
- Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.,Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yoshihisa Fujino
- Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Atsuko Ikenouchi
- Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.,Medical Center for Dementia, University Hospital of Occupational and Environmental Health, Kitakyushu, Japan
| | - Naoto Adachi
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Yukihisa Kubota
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Takaharu Azekawa
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Hitoshi Ueda
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Koji Edagawa
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Eiichi Katsumoto
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Eiichiro Goto
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Seiji Hongo
- The Japanese Association of Neuro-Psychiatric Clinics, Tokyo, Japan
| | - Masaki Kato
- The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan.,Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan
| | - Takashi Tsuboi
- The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan.,Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan
| | - Norio Yasui-Furukori
- The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan.,Department of Psychiatry, Dokkyo Medical University, Tochigi, Japan
| | - Atsuo Nakagawa
- The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan.,Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Toshiaki Kikuchi
- The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan.,Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Koichiro Watanabe
- The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan.,Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan
| | - Reiji Yoshimura
- Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.,The Japanese Society of Clinical Neuropsychopharmacology, Tokyo, Japan
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Antipsychotic Polypharmacy Is Associated With Adverse Drug Events in Psychiatric Inpatients: The Japan Adverse Drug Events Study. J Clin Psychopharmacol 2021; 41:397-402. [PMID: 34108429 PMCID: PMC8244930 DOI: 10.1097/jcp.0000000000001416] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Antipsychotic (AP) polypharmacy (APP), the coprescription of more than 1 AP, is frequently practiced in psychiatric inpatients and is considered to be a risk factor for adverse drug events (ADEs). However, the association between APP and ADEs among psychiatric inpatients has not been well investigated. METHODS The Japan Adverse Drug Events (JADE) study was a series of cohort studies conducted in several clinical settings. In particular, the JADE study for psychiatric inpatients was a retrospective cohort study of 448 psychiatric inpatients with a cumulative 22,733 patient-days. We investigated the relationship between APP, defined as a concurrent prescription of 2 or more APs and ADEs. We also assessed the relationship between potential risk factors for ADEs due to APs. RESULTS Among the 448 patients included in this study, 106 patients (24%) had APP and the remaining 342 patients were prescribed 1 AP or none. Risperidone was the most frequent drug (25%, 109/442 AP prescriptions) used, and levomepromazine was most frequently prescribed as a concurrent medication with other APs (91%, 29/32). The median number of ADEs among the patients with APP was significantly higher than in those without APP (P = 0.001). Antipsychotic polypharmacy was a risk factor for the occurrence of first (adjusted hazard ratio, 1.54; 95% confidence interval, 1.15-2.04) and second (adjusted hazard ratio, 1.99; 95% confidence interval, 1.40-2.79) ADEs. CONCLUSIONS Antipsychotic polypharmacy was a risk factor for the occurrence of single and multiple ADEs. Antipsychotic polypharmacy should be conservatively and minimally practiced.
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Qureshi MM, Young AH. Hamlet's augury: how to manage discontinuation of mood stabilizers in bipolar disorder. Ther Adv Psychopharmacol 2021; 11:20451253211000612. [PMID: 33796268 PMCID: PMC7968017 DOI: 10.1177/20451253211000612] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 01/27/2021] [Indexed: 01/26/2023] Open
Abstract
Research has generated good quality evidence about the treatment and management of bipolar disorder in acute and, to some degree, sub-acute/continuation phases. This has informed various guidelines about the treatment and management of bipolar disorder (BD). However, for the long-term or maintenance phase of illness, most guidelines peter out and, in the absence of sufficiently high-quality research evidence, remain vague. This is particularly evident for the important clinical question of discontinuing mood stabilizing pharmacological agents after a period of remission has been achieved. The aim of this review is to put together current existing evidence about discontinuing mood stabilizers after a period of remission in order to come up with a structured and coherent strategy for managing such discontinuation and to make recommendations for future research. To this end, we reviewed the main relevant treatment guidelines and subsequent evidence following the publication of these guidelines. The current recommended long-term treatment of BD is usually considered within the same principles applicable to any chronic health condition (e.g. hypertension or diabetes) where the focus is on continuing treatment at minimum effective medication dose often life-long, switching to alternative choice of medication due to side-effects and very few, if any, indications for complete cessation. However, in the absence of strong evidence on long-term treatment and the high rate of non-concordance in BD, medication discontinuation is a very important aspect of the treatment that should be given due consideration at every aspect of the treatment.
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Affiliation(s)
- Mutahira M Qureshi
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO72, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK
| | - Allan H Young
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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Besag FMC, Vasey MJ, Sharma AN, Lam ICH. Efficacy and safety of lamotrigine in the treatment of bipolar disorder across the lifespan: a systematic review. Ther Adv Psychopharmacol 2021; 11:20451253211045870. [PMID: 34646439 PMCID: PMC8504232 DOI: 10.1177/20451253211045870] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 08/25/2021] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Bipolar disorder (BD) is a cyclic mood disorder characterised by alternating episodes of mania/hypomania and depression interspersed with euthymic periods. Lamotrigine (LTG) demonstrated some mood improvement in patients treated for epilepsy, leading to clinical studies in patients with BD and its eventual introduction as maintenance therapy for the prevention of depressive relapse in euthymic patients. Most current clinical guidelines include LTG as a recommended treatment option for the maintenance phase in adult BD, consistent with its global licencing status. AIMS To review the evidence for the efficacy and safety of LTG in the treatment of all phases of BD. METHODS PubMed was searched for double-blind, randomised, placebo-controlled trials using the keywords: LTG, Lamictal, 'bipolar disorder', 'bipolar affective disorder', 'bipolar I', 'bipolar II', cyclothymia, mania, manic, depression, depressive, 'randomised controlled trial', 'randomised trial', RCT and 'placebo-controlled' and corresponding MeSH terms. Eligible articles published in English were reviewed. RESULTS Thirteen studies were identified. The strongest evidence supports utility in the prevention of recurrence and relapse, particularly depressive relapse, in stabilised patients. Some evidence suggests efficacy in acute bipolar depression, but findings are inconsistent. There is little or no strong evidence in support of efficacy in acute mania, unipolar depression, or rapid-cycling BD. Few controlled trials have evaluated LTG in bipolar II or in paediatric patients. Indications for safety, tolerability and patient acceptability are relatively favourable, provided there is slow dose escalation to reduce the probability of skin rash. CONCLUSION On the balance of efficacy and tolerability, LTG might be considered a first-line drug for BD, except for acute manic episodes or where rapid symptom control is required. In terms of efficacy alone, however, the evidence favours other medications.
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Affiliation(s)
- Frank M C Besag
- East London NHS Foundation Trust, 9 Rush Court, Bedford MK40 3JT, UK
| | | | - Aditya N Sharma
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Ivan C H Lam
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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50
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Kato T, Ishigooka J, Miyajima M, Watabe K, Fujimori T, Masuda T, Higuchi T, Vieta E. Double-blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression. Psychiatry Clin Neurosci 2020; 74:635-644. [PMID: 32827348 PMCID: PMC7756283 DOI: 10.1111/pcn.13137] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 07/21/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022]
Abstract
AIM Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan. METHODS Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (-13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (-12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (-10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control. CONCLUSION Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.
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Affiliation(s)
- Tadafumi Kato
- Department of Psychiatry, Juntendo University, Tokyo, Japan.,Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Center for Brain Science, Wako, Japan
| | | | | | - Kei Watabe
- Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan
| | - Tomohiro Fujimori
- Sumitomo Dainippon Pharma Co., Ltd., Tokyo, Japan.,Sunovion Pharmaceuticals Inc., Marlborough, USA
| | | | - Teruhiko Higuchi
- Japan Depression Center, Tokyo, Japan.,The National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
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