Ondansetron Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder: A Randomized Placebo-Controlled Clinical Trial

Background: Serotonin and dopamine are involved in the development of obsessive-compulsive disorder (OCD). Approximately 40% of OCD patients do not respond to the first-line therapy of treatment using selective serotonin reuptake inhibitors. Reportedly, the response to the treatment is increased by enhancing dopamine blockers. Objectives: The purpose of this study was to evaluate the efficacy and immunogenicity of ondansetron as a booster in the treatment of OCD patients. Methods: The present double-blind, randomized clinical trial (RCT) was conducted on 40 patients (16 males and 24 females) aged 18 to 60 years who met the DSM-V-TR-based OCD diagnostic criteria and had a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The patients were randomized to receive standard treatment and ondansetron (8 mg/day) or placebo for 12 weeks. They were examined using Y-BOCS and side-effect checklist at baseline, fourth, eighth, and twelfth weeks. Results: The patients in both groups were homogeneous and comparable in terms of age, marital sex status, type of obsession, anxiety, depression, age at the onset of disease, and the duration of disease. The Y-BOCS scores in the intervention and placebo groups were 27.15 +/- 3.94 vs. 26.15 +/- 4.94 at baseline, 25.40 +/- 3.75 vs. 25.00 +/- 4.79 in the fourth week, 20.85 +/- 3.69 vs. 24.05 +/- 4.97 (P = 0.026) in the eighth week, and 17.95 +/- 3.43 vs. 21.65 +/- 4.85 (P = 0.008) in the twelfth week, respectively. Significant changes occurred between the two groups at weeks 8 and 12; the difference between the two groups was significant (P = 0.015), whereas no significant difference was observed between the two groups before week 8. Conclusions: This 12-week, double-blind, and randomized clinical trial showed that ondansetron was a booster agent with a significant effect on patients with moderate to severe OCD. This study also showed that ondansetron is generally well tolerated by OCD patients. The response to the treatment also increased from the eighth week of treatment onwards. The severity of the disease was decreased at the end of the ondansetron intervention. The adjunct ondansetron treatment was recommended for OCD patients