O5.4. PROBLEM GAMBLING ASSOCIATED WITH ARIPIPRAZOLE: A NESTED CASE-CONTROL STUDY IN A FIRST-EPISODE PSYCHOSIS COHORT USING A SYSTEMATIC PHARMACOVIGILANCE APPROACH

Aripiprazole is an antipsychotic drug widely prescribed for patients with schizophrenia and first-episode psychosis (FEP). Recently, Health Canada and the FDA have issued vigilance notices regarding the occurrence of problem gambling associated with aripiprazole. However, despite the case reports of problem gambling linked with aripiprazole in schizophrenia patients found in the literature, our critical review demonstrates that we can’t conclude on the imputability of aripiprazole at this point. Considering that the consequences of problem gambling can be significant, it is essential to evaluate this association more thoroughly, with the conduction of well-designed studies. The main objective of this study is to evaluate the association between aripiprazole exposure and problem gambling in patients treated for a FEP at our clinic. The secondary objectives are to identify risk factors for the emergence of problem gambling in FEP patients and to determine the factors that distinguish patients developing problem gambling with aripiprazole from those who do not develop it (e.g. pharmaceutical formulation, dosage, duration of exposure). This is a nested case-control study combined with a systematic imputability assessment using the Naranjo scale examining the association between aripiprazole use and problem gambling among FEP patients. Records of 219 patients treated at our FEP clinic between November 1st, 2015, and February 1st, 2018, were reviewed. Within this cohort, 14 cases of problem gambling were identified, and 56 control subjects were matched for gender and index date (1:4 ratio). Univariate and multivariate conditional logistic regressions were used to examine the association between the use of aripiprazole (duration, dosage and formulation) and the risk of problem gambling, while adjusting for potentially confounding factors such as age, relationship status and Cluster B personality traits. Use of aripiprazole was associated with more than a 10-fold increased risk of problem gambling (adjusted odds ratio [OR], 10.9; 95% confidence interval [CI], 1.5 - 357.9; p = 0.01) as compared with other antipsychotics. Among aripiprazole users, the risk of problem gambling was greater in patients who were older, in a relationship, employed, had Cluster B personality traits and a history of gambling. When comparing aripiprazole use in both case and control groups, there was no relationship observed between the route of administration, dosage or treatment duration with the risk of problem gambling. This study extends previous evidence documenting the association between aripiprazole and problem gambling. It is the first to examine this relationship in a FEP cohort, in which aripiprazole use is widely spread. Based on the present results, we firmly believe that the implementation of a systematic evaluation for gambling history in all FEP patients is required at entrance in FEP programs. Indeed, patients with a history of gambling seem particularly vulnerable to the development of a full-blown problem gambling when prescribed aripiprazole. Future studies conducted with larger samples of patients are warranted to further assess the risk-benefit profile of aripiprazole and to identify at-risk patients to better guide on-field clinicians.

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