Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Mar 1;182(3):285-296.
doi: 10.1176/appi.ajp.20240294. Epub 2025 Jan 29.

Randomized Controlled Trial of the Effects of High-Dose Ondansetron on Clinical Symptoms and Brain Connectivity in Obsessive-Compulsive and Tic Disorders

Emily R Stern  1 , Katherine A Collins  1 , Laura B Bragdon  1 , Goi Khia Eng  1 , Nicolette Recchia  1 , Barbara J Coffey  1 , Evan Leibu  1 , James W Murrough  1 , Russell H Tobe  1 , Dan V Iosifescu  1 , Katherine E Burdick  1 , Wayne K Goodman  1
Affiliations
Randomized Controlled Trial

Randomized Controlled Trial of the Effects of High-Dose Ondansetron on Clinical Symptoms and Brain Connectivity in Obsessive-Compulsive and Tic Disorders

Emily R Stern et al. Am J Psychiatry. .

Abstract

Objective: Sensory phenomena (SP) are aversive sensations driving repetitive behaviors in obsessive-compulsive disorder (OCD) and Tourette's disorder that are not well addressed by standard treatments. SP are related to the functioning of an interoceptive-sensorimotor circuit that may be modulated by the 5-HT3 receptor antagonist ondansetron. The present study employed an experimental medicine approach to test the effects of 4 weeks of high-dose ondansetron compared to placebo on SP severity and brain connectivity in a cohort of individuals with OCD and/or Tourette's disorder.

Methods: Of 51 participants who completed the study, 27 were assigned to receive 24 mg/day of ondansetron and 24 to receive placebo. Analyses examined changes in SP severity and, for participants with OCD, overall OCD severity from baseline to final visit. Functional MRI data were collected at both visits for analysis of intrinsic functional connectivity metrics characterizing global correlation (reflecting area "hubness") and local correlation (reflecting near-neighbor coherence).

Results: There were no significant differences between ondansetron and placebo in the reduction of SP or overall OCD severity in the full sample. In a subsample of participants with OCD taking concomitant serotonin reuptake inhibitors (SRIs), ondansetron was associated with a significant decrease in overall OCD severity and global connectivity of the medial sensorimotor cortex compared with placebo. Longitudinal reductions in SP severity were related to decreases in right sensorimotor hubness in both groups, and to brainstem local coherence only in participants taking ondansetron.

Conclusions: There was no effect of high-dose ondansetron on SP. However, when used as an augmentation to SRIs, ondansetron reduced overall OCD severity, which may be related to changes in the "hubness" of the sensorimotor cortex. Ondansetron's ability to modulate brainstem connectivity may underlie its variable effectiveness in reducing SP.

Keywords: Clinical Drug Studies; Neuroimaging; Obsessive-Compulsive Disorder (OCD); Ondansetron; Tourette’s Disorder.

PubMed Disclaimer

Conflict of interest statement

Dr. Collins has served as a consultant for A. Stein Regulatory Affairs Consulting, Cronos Clinical Consulting Services, MedAvante-ProPhase, and Relmada Therapeutics. Dr. Coffey has received research support from Emalex, the New Venture Fund, and Zynerba; she has received honoraria from the American Academy of Child and Adolescent Psychiatry, Harvard Medical School/Psychiatry Academy, and Partners Healthcare; and she serves on advisory boards for Galen Mental Health, Skyland Trail, and the Tourette’s Association of America. Dr. Murrough has served as a consultant for Biohaven Pharmaceuticals, Clexio Biosciences, Cliniclabs, Compass Pathfinder, KetaMed, LivaNova, Merck, and Xenon Pharmaceuticals. Dr. Tobe has received grant support from Axial Therapeutics, F. Hoffmann-La Roche AG, Janssen Research & Development, and MapLight Therapeutics and has attended advisory boards for F. Hoffmann-La Roche. Dr. Iosifescu has served as a consultant for Alkermes, Allergan, Angelini, Autobahn, Axsome, Biogen, Boehringer Ingelheim, the Centers for Psychiatric Excellence, Clexio, Delix, Jazz, LivaNova, Lundbeck, Neumora, Otsuka, Precision Neuroscience, Relmada, Sage, and Sunovion; and he has received grant support (paid to his institutions) from Alkermes, AstraZeneca, BrainsWay, LiteCure, NeoSync, Otsuka, Roche, and Shire. Dr. Burdick has received honoraria from Breakthrough Discoveries for Thriving With Bipolar Disorder (BD-squared) and as a scientific advisory board member for Merck. Dr. Goodman receives royalties for OCDscales and Nview. The other authors report no financial relationships with commercial interests.

Similar articles

See all similar articles

Publication types

MeSH terms

Substances

LinkOut - more resources