Antipsychotic-associated obsessive-compulsive symptoms and disorder: scoping review of mechanisms, comparative...

Antipsychotic agents play a paradoxical role in obsessive-compulsive phenomena, augmenting selective serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder yet also inducing or worsening obsessive-compulsive symptoms, mainly in psychotic but also in mood disorders. How strongly individual agents are implicated has not been compared.

To map the distribution and density of evidence on antipsychotic-associated obsessive-compulsive symptoms across all agents, including those without induction evidence, and to synthesise causality indicators and management strategies.

A scoping review following Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. PubMed/MEDLINE and Scopus were searched from inception to December 2025, supplemented by two regulatory pharmacovigilance databases (United States FDA Adverse Event Reporting System and World Health Organization VigiBase). Prespecified operational definitions, a four-dimension triangulation framework and a standardised dose metric were applied. Registered on the Open Science Framework (DOI: 10.17605/OSF.IO/R8ZFA).

Eighty-eight primary studies were included. Clozapine carried the densest, most consistent evidence (de novo prevalence 5.9-44.3%; total up to 77.9%); in the one controlled cohort with a drug-free comparator, the number needed to harm for clozapine (at least 6 months) was approximately 4 (95% CI: 2-8). Olanzapine and risperidone were intermediate, and predominantly antidopaminergic agents showed minimal literature. Pharmacovigilance placed aripiprazole, not clozapine, highest, discordant with its sparse clinical literature, indicating that the gradient partly reflects research concentration. Genetic associations supported a serotonergic-glutamatergic framework.

Evidence for inducing obsessive-compulsive symptoms varies across antipsychotics, being most consistent for clozapine and least for predominantly dopamine-blocking agents. Brief routine screening and a pragmatic response pathway may be considered in clozapine services, with vigilance for other agents as evidence accrues.