Ondansetron plus SRI eases OCD severity

Treatment with high-dose ondansetron shows no effect on sensory phenomena (SP) in patients with obsessive-compulsive disorder (OCD), according to a study.

However, when used in combination with serotonin reuptake inhibitors (SRIs), ondansetron results in a significant reduction in overall OCD severity, which may be associated with changes in the “hubness” of the sensorimotor cortex.

“Ondansetron’s ability to modulate brainstem connectivity may underlie its variable effectiveness in reducing SP,” the investigators said.

Fifty-one participants with OCD and/or Tourette’s disorder completed this study. Of these, 27 were assigned to receive ondansetron 24 mg/day and 24 to placebo. Analyses were carried out to examine changes in SP severity and, for those with OCD, overall OCD severity from baseline to final visit.

Finally, the investigators collected functional MRI data at both visits to analyse the intrinsic functional connectivity metrics characterizing global correlation (reflecting area hubness) and local correlation (reflecting near-neighbor coherence).

No significant differences were observed in the reduction of SP or overall OCD severity between the ondansetron and placebo groups. However, in a subset of patients with OCD taking concomitant SRIs, ondansetron correlated with a substantial decrease in overall OCD severity and global connectivity of the medial sensorimotor cortex relative to placebo.

Moreover, longitudinal reductions in SP severity were associated with reductions in right sensorimotor hubness in both groups and to brainstem local coherence only in those treated with ondansetron.

“SP are aversive sensations driving repetitive behaviours in OCD and Tourette’s disorder that are not well addressed by standard treatments,” the investigators said. “SP are related to the functioning of an interoceptive-sensorimotor circuit that may be modulated by the 5-HT₃ receptor antagonist ondansetron.”