Patterns of pharmacotherapy for bipolar disorder: A GBC survey

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Abstract

Objectives

To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized individuals with BD in North America, Europe, and Australia.

Methods

Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns.

Results

This study included 10,351 individuals from North America ( n = 3985), Europe ( n = 3822), and Australia ( n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60%; vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort.

Conclusions

Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD.

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Canadian Network for Mood and Anxiety Treatments ( CANMAT ) and International Society for Bipolar Disorders ( ISBD ) 2018 guidelines for the management of patients with bipolar disorder

Lakshmi Yatham, Sidney H Kennedy, Sagar Parikh … (2018)

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

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Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

Jeffrey A Lieberman, T. Stroup, Joseph P. McEvoy … (2005)

The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism. Copyright 2005 Massachusetts Medical Society.

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Bipolar disorders

Roger McIntyre, Michael Berk, Elisa Brietzke … (2020)

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10-20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.

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Author and article information

Contributors

Balwinder Singh: (View ORCID Profile)

Anastasia K. Yocum: (View ORCID Profile)

Rebecca Strawbridge: (View ORCID Profile)

Katherine E. Burdick: (View ORCID Profile)

Sarah H. Sperry: (View ORCID Profile)

Giovanna Fico: (View ORCID Profile)

Eduard Vieta: (View ORCID Profile)

Ophelia Godin: (View ORCID Profile)

Marion Leboyer: (View ORCID Profile)

Etain Bruno: (View ORCID Profile)

Ivy F. Tso: (View ORCID Profile)

Brandon J. Coombes: (View ORCID Profile)

Lana J. Williams: (View ORCID Profile)

Kamyar Keramatian: (View ORCID Profile)

Janice M. Fullerton: (View ORCID Profile)

Ana C. Andreazza: (View ORCID Profile)

Peter P. Zandi: (View ORCID Profile)

Joanna M. Biernacka: (View ORCID Profile)

Journal

Title: Bipolar Disorders

Abbreviated Title: Bipolar Disorders

Publisher: Wiley

ISSN (Print): 1398-5647

ISSN (Electronic): 1399-5618

Publication date (Electronic): July 18 2023

Affiliations

[1 ] Mayo Clinic, Department of Psychiatry & Psychology Mayo Clinic Rochester Minnesota USA

[2 ] Department of Psychiatry University of Michigan Ann Arbor Michigan USA

[3 ] Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience King's College London London UK

[4 ] Harvard Medical School Brigham and Women's Hospital Boston Massachusetts USA

[5 ] Dauten Family Center for Bipolar Treatment Innovation Harvard Medical School, Massachusetts General Hospital Boston Massachusetts USA

[6 ] Bipolar and Depressive Disorders Unit, Institute of Neuroscience Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM Barcelona Catalonia Spain

[7 ] Local Health Unit Umbria 1, Department of Mental Health Mental Health Center of Perugia Perugia Italy

[8 ] INSERM U955, IMRB, Translational Neuro‐Psychiatry, Fondation FondaMental Univ Paris Est Créteil Créteil France

[9 ] Département Médico‐Universitaire de Psychiatrie et d'Addictologie (DMU IMPACT) APHP, Hôpitaux Universitaires Henri Mondor, Fédération Hospitalo‐Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT) Créteil France

[10 ] Groupe Hospitalo‐universitaire AP‐HP Nord, DMU Neurosciences, Hôpital Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, INSERM UMRS 1144 Université de Paris, AP‐HP Paris France

[11 ] Department of Psychiatry & Behavioral Health The Ohio State University Columbus Ohio USA

[12 ] Department of Quantitative Health Sciences Mayo Clinic Rochester Minnesota USA

[13 ] IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health Deakin University Geelong Victoria Australia

[14 ] Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry The University of Melbourne Melbourne Victoria Australia

[15 ] Department of Psychiatry University of British Columbia Vancouver Canada

[16 ] Neuroscience Research Australia Randwick, Sydney New South Wales Australia

[17 ] School of Medical Sciences, Faculty of Medicine University of New South Wales Sydney New South Wales Australia

[18 ] School of Psychiatry, Faculty of Medicine University of New South Wales Sydney New South Wales Australia

[19 ] NORMENT Centre, Division of Mental Health and Addiction University of Oslo and Oslo University Hospital Oslo Norway

[20 ] Department of Pharmacology & Toxicology, Temerty Faculty of Medicine University of Toronto Toronto Canada

[21 ] Department of Psychiatry and Behavioral Sciences Johns Hopkins School of Medicine Baltimore Maryland USA

[22 ] The Milken Institute Washington District of Columbia USA

Article

DOI: 10.1111/bdi.13366

PubMed ID: 37463846

SO-VID: c4cd2b11-9f12-4f9d-9f3d-a0e9965d4deb

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http://creativecommons.org/licenses/by/4.0/

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Patterns of pharmacotherapy for bipolar disorder: A GBC survey

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Abstract

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Most cited references 53

Canadian Network for Mood and Anxiety Treatments ( CANMAT ) and International Society for Bipolar Disorders ( ISBD ) 2018 guidelines for the management of patients with bipolar disorder

Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.

Bipolar disorders

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