How Common is Compulsive Gambling on Aripiprazole?

Dopamine dysregulation is a psychiatric syndrome worth understanding

STUDY: Corbeil O et al, European Psychiatry 2026;69(1):e29

STUDY TYPE: Prospective multicentre cohort study

FUNDING: Fonds de Recherche du Québec – Société et Culture

Background

The third generation antipsychotics are partial agonists at dopamine D3: Aripiprazole, brexpiprazole, and cariprazine. By activating the reward center, they can cause problematic gambling, hypersexuality, overspending, and punding, collectively known as hedonistic or dopamine dysregulation syndrome. Substance use is not part of the syndrome, though overeating can be.

The syndrome is unrelated to mania, and the patients don’t present with manic symptoms other than excessive pleasurable activity. Selective D3 agonists like pramipexole, ropinirole, and levodopa also cause it.

The Study

This Canadian cohort study followed 520 young adults (mean age 24.6; 29% women) with first-episode psychosis at two early intervention programs for an average of 16 months, screening systematically for problem gambling using the Problem Gambling Severity Index (PGSI) every six months.

Eighteen developed problem gambling during follow-up (2.6 per 100 person-years). Thirteen of those 18 cases occurred during aripiprazole treatment; 289 patients took aripiprazole, making the risk 4.5%, or 4.7-fold higher than off aripiprazole (after adjusting for confounders; with confidence limits 1.6–13.9).

Third-generation antipsychotics as a class carried a 6-fold risk. First- and second-generation antipsychotics showed no significant association.

Limitations: Small sample, only 18 cases, confounding can’t be excluded.

Comparison to Pramipexole

Aripiprazole and pramipexole are both effective in treatment-resistant depression, but we don’t have direct comparisons to tell us which is riskier.

Their risks were similar in large study of the Swedish population, and aripiprazole’s rate in today’s study of schizophrenia (4.5%) is similar to the rate for pramipexole in depression (1-3%).

But the risk varies by population. In Parkinson’s disease, pramipexole’s risk is much higher (15-20%).

In this study, people with a past history of gambling (even if non-problematic) or of stimulant use disorder had a greater risk.

Practice Implications

1. Before starting a D3 agonist, advice patients that it can increase their motivation and drive. Often the effects are benign — sorting bookshelf or cleaning the garage — but the hedonic drive can cause problems 1-5% of the time.
2. The risk appears similar for pramipexole and aripiprazole, and greater for aripiprazole than other D3 antipsychotics.