Negative symptomatology and clozapine-induced obsessive-compulsive symptoms: a cross-sectional analysis

Eur Arch Psychiatry Clin Neurosci. 2025 May 16. doi: 10.1007/s00406-025-02021-z. Online ahead of print.

ABSTRACT

Obsessive-compulsive symptoms (OCS) frequently manifest in individuals with schizophrenia, affecting their prognosis and quality of life. The etiology of OCS in schizophrenia is complex, with theories ranging from subtype-specific manifestations to pharmacological influences. Notably, clozapine has been associated with a higher prevalence of OCS. However, the clinical factors influencing clozapine-induced OCS remain unclear. This cross-sectional study recruited individuals diagnosed with schizophrenia who were using clozapine, as well as a comparison group of individuals diagnosed with schizophrenia who were using other second-generation antipsychotics (SGA). Clinical assessments included OCS which were quantified using the Obsessive-Compulsive Inventory-Revised (OCI-R). 189 Participants were recruited, of whom 129 were taking clozapine and 60 other atypical antipsychotics. Statistical analyses, including moderated regression modeling, identified clinical factors influencing OCS occurrence. Clozapine users exhibited significantly higher OCI-R scores compared to non-clozapine users (p = 0.001). Moderated regression analysis revealed a moderating effect of negative symptom severity, indicating that when negative symptoms increased, the difference in OCI-R scores between clozapine and non-clozapine groups decreased. Other factors like duration of illness, medication duration, and psychopathology severity did not significantly moderate the group differences in OCI-R scores. As negative symptoms worsened, the impact of clozapine on OCS lessened, a pattern not seen with other antipsychotics. This suggests that clozapine’s effect on OCS is specific and influenced by different mechanisms. The study recommends screening for OCS in patients with mild negative symptoms and further research into biological markers to better understand clozapine-induced OCS.

PMID:40377660 | DOI:10.1007/s00406-025-02021-z