Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study

Markku Lähteenvuo; Tapio Paljärvi; Antti Tanskanen; Heidi Taipale; Jari Tiihonen

doi:10.1192/bjp.2023.75

Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study

Br J Psychiatry. 2023 Oct;223(4):456-464. doi: 10.1192/bjp.2023.75.

Authors

Markku Lähteenvuo¹, Tapio Paljärvi¹, Antti Tanskanen², Heidi Taipale³, Jari Tiihonen⁴

Affiliations

¹ Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
² Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; and Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska Institutet, Stockholm, Sweden.
³ Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; and Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska Institutet, Stockholm, Sweden; and School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
⁴ Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; and Neuroscience Center, University of Helsinki, Helsinki, Finland.

Abstract

Background: Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse?

Aims: To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder.

Method: Register-based cohort study including all Finnish residents aged 16-65 with a diagnosis of bipolar disorder from in-patient care, specialised out-patient care, sickness absence and disability pensions registers between 1996 and 2018, with a mean follow-up of 9.3 years (s.d. = 6.4). Antipsychotic and mood stabiliser use was modelled using the PRE2DUP method and risk for hospital admission for psychiatric and non-psychiatric reasons when using versus not using medications was estimated using within-individual Cox models.

Results: Among 60 045 individuals (56.4% female; mean age 41.7 years, s.d. = 15.8), the five medications associated with lowest risk of psychiatric admissions were olanzapine long-acting injection (LAI) (aHR = 0.54, 95% CI 0.37-0.80), haloperidol LAI (aHR = 0.62, 0.47-0.81), zuclopenthixol LAI (aHR = 0.66, 95% CI 0.52-0.85), lithium (aHR = 0.74, 95% CI 0.71-0.76) and clozapine (aHR = 0.75, 95% CI 0.64-0.87). Only ziprasidone (aHR = 1.26, 95% CI 1.07-1.49) was associated with a statistically higher risk. For non-psychiatric (somatic) admissions, only lithium (aHR = 0.77, 95% CI 0.74-0.81) and carbamazepine (aHR = 0.91, 95% CI 0.85-0.97) were associated with significantly reduced risk, whereas pregabalin, gabapentin and several oral antipsychotics, including quetiapine, were associated with an increased risk. Results for a subcohort of first-episode patients (26 395 individuals, 54.9% female; mean age 38.2 years, s.d. = 13.0) were in line with those of the total cohort.

Conclusions: Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions.

Keywords: Bipolar affective disorders; epidemiology; lithium.; pharmacotherapy; treatment effectiveness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antipsychotic Agents* / therapeutic use
Bipolar Disorder* / drug therapy
Clozapine* / therapeutic use
Cohort Studies
Female
Humans
Lithium / therapeutic use
Male

Substances

Lithium
Antipsychotic Agents
Clozapine