Randomized controlled trial of add-on Fluoxetine versus usual antipsychotic treatment in obsessive compulsive symptoms in schizophrenia

Indian J Psychiatry. 2025 Jul;67(7):666-674. doi: 10.4103/indianjpsychiatry_757_24. Epub 2025 Jul 15.

Abstract

Background: Schizophrenia can coexist with obsessive-compulsive symptoms (OCSs). This study aimed to assess the efficacy of adding Fluoxetine-gold standard for the treatment of obsessive-compulsive disorder to the treatment regimen of patients with schizophrenia and OCS.

Methods: Patients diagnosed with schizophrenia (according to ICD-11) and OCS (assessed via the Y-BOCS Checklist) were randomized to either the Add-on Fluoxetine (received Fluoxetine in addition to their ongoing antipsychotic treatment) or the Antipsychotic only (continued with standard therapy) using a computer-generated random number table and assessed using PANSS, CGI-global impression, and SOFAS. Baseline assessments were conducted to evaluate sociodemographic and clinical factors and the severity of OCS. Both groups were monitored over 8 weeks for changes in psychotic and obsessive-compulsive symptoms.

Results: Seventy patients of schizophrenia with OCS were recruited, 35 in each group. Both groups demonstrated significant improvement over 8 weeks in psychotic and obsessive-compulsive symptoms. The Add-on Fluoxetine exhibited earlier and more pronounced symptom improvements. A significant difference was found in the YBOCS compulsion score, with a median score of 8 (7-10) in the Add-on Fluoxetine and 11 (9.5-12) in the Antipsychotic only (P value of 0.003). Add-on Fluoxetine had a lower median score on CGI global improvement, 3 (3-3), and CGI efficacy index, 10 (10-10), than the Antipsychotic only, 4 (3-4) and 14 (10-14), respectively (P value < 0.001). Fluoxetine was well tolerated, with minimal reported side effects.

Conclusions: The findings suggest that adjunctive Fluoxetine treatment led to early resolution of psychopathology and improved overall outcomes in schizophrenia with co-occurring OCS.

Keywords: CGI global improvement; Fluoxetine; ICD-11; OCS; SSRI; Schizophrenia; obsessive-compulsive symptoms; selective serotonin reuptake inhibitor.