S. Lindström, M. Wolfschlag, A. Håkansson, J. Berge
BACKGROUND: Pramipexole, a dopamine agonist, has demonstrated antidepressant efficacy as an augmentation strategy in unipolar and bipolar depression. However, dopaminergic treatments are associated with impulse control disorders, including gambling disorder, and evidence regarding behavioural risks in psychiatric populations remains limited. METHODS: We conducted a nationwide register-based cohort study including individuals with psychiatric disorders who were prescribed pramipexole between 2006 and 2021. Cumulative pramipexole exposure was quantified longitudinally and analysed as a time-varying variable. The primary outcome was incident, clinically diagnosed gambling disorder identified in specialised healthcare registers. Associations were examined using Cox proportional hazards models, adjusting for relevant sociodemographic and clinical covariates. RESULTS: During follow-up, incident gambling disorder was rare but occurred disproportionately among individuals with higher cumulative pramipexole exposure. A clear dose-response relationship was observed, with progressively increasing risk across exposure categories. Individuals with bipolar disorder exhibited a particularly elevated risk compared with other psychiatric diagnostic groups. CONCLUSIONS: In this nationwide psychiatric cohort, cumulative exposure to pramipexole was associated with an increased risk of incident gambling disorder, with evidence of a dose-response relationship. Although the absolute risk of clinically diagnosed gambling disorder was low-likely reflecting substantial underdiagnosis-the clinical consequences of gambling disorder are considerable. These findings complement trial evidence by highlighting behavioural risks associated with long-term dopaminergic treatment in routine psychiatric care and underscore the importance of exposure-aware prescribing and systematic monitoring, particularly among individuals with bipolar disorder.