Aripiprazole and Other Third-Generation Antipsychotics as a Risk Factor for Impulse Control Disorders

Abstract Background Increasing evidence suggests an association between third-generation antipsychotics (TGAs) and impulse control disorders (ICDs). This is thought to be due to their partial agonism of dopamine receptors. However, neither the relative nor absolute risks of ICDs in those prescribed TGAs are well established. To inform clinical practice, this systematic review and meta-analysis summarizes and quantifies the current evidence for an association. Methods An electronic search of Medline, PsychINFO, EMBASE, and the Cochrane Clinical Trials Database was undertaken from database inception to November 2022. Three reviewers screened abstracts and reviewed full texts for inclusion. A random-effects meta-analysis was conducted with eligible studies. Results A total of 392 abstracts were retrieved, 214 remained after duplicates were removed. Fifteen full texts were reviewed, of which 8 were included. All 8 studies found that TGAs were associated with increased probability of ICDs. Risk of bias was high or critical in 7 of 8 studies. Three studies were included in the pooled analysis for the primary outcome, 2 with data on each of aripiprazole, cariprazine, and brexpiprazole. Exposure to TGAs versus other antipsychotics was associated with an increase in ICDs (pooled odds ratio, 5.54; 2.24–13.68). Cariprazine and brexpiprazole were significantly associated with ICDs when analyzed individually. Aripiprazole trended toward increased risk, but very wide confidence intervals included no effect. Conclusions Third-generation antipsychotics were associated with increased risk of ICDs in all studies included and pooled analysis. However, the risk of bias is high, confidence intervals are wide, and the quality of evidence is very low for all TGAs examined.