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The following is a summary of “Randomized Controlled Trial of the Effects of High-Dose Ondansetron on Clinical Symptoms and Brain Connectivity in Obsessive-Compulsive and Tic Disorders,” published in the January 2025 issue of Psychiatry by Stern et al. 

Sensory phenomena (SP) drive repetitive behaviors in obsessive-compulsive disorder (OCD) and Tourette’s but remain poorly managed. They involve an interoceptive-sensorimotor circuit modulated by ondansetron. 

Researchers conducted a retrospective study to assess high-dose ondansetron’s effects on SP severity and brain connectivity in OCD and Tourette’s disorder, comparing it to a placebo over 4 weeks. 

They assigned 51 participants to either 24 mg/day of ondansetron (27 participants) or placebo (24 participants). Analyzes examined changes in SP severity and overall OCD severity for participants with OCD. Functional MRI data were collected at baseline and final visit to analyze intrinsic functional connectivity, including global correlation (reflecting area “hubness”) and local correlation (reflecting near-neighbor coherence). 

The results showed no significant differences between ondansetron and placebo in reducing SP or overall OCD severity in the full sample. In the OCD subsample of taking serotonin reuptake inhibitors (SRIs), ondansetron significantly decreased overall OCD severity and global connectivity of the medial sensorimotor cortex compared to placebo. Longitudinal reductions in SP severity were linked to decreases in right sensorimotor hubness in both groups and to brainstem local coherence in participants taking ondansetron. 

Investigators found no effect of high-dose ondansetron on SP. However, as an augmentation to SRIs, ondansetron reduced overall OCD severity, potentially related to changes in sensorimotor cortex hubness and brainstem connectivity. 

Source: psychiatryonline.org/doi/10.1176/appi.ajp.20240294