A non-antidepressant option shows efficacy
STUDY: Rostami H et al, J Clin Psychopharmacol 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Ahvaz Jundishapur University of Medical Sciences
Background
OCD and bipolar mingle together, at a 10-fold higher rate than the general population. SSRIs can worsen bipolar disorder, so non-antidepressant options like psychotherapy, TMS, ondansetron, topiramate, lamotrigine, celecoxib, and quetiapine are needed.
Memantine, an NMDA receptor antagonist approved for Alzheimer’s disease, targets glutamate instead and shows promise in OCD. This is the first randomized trial to test it in bipolar disorder.
The Study
- 46 adults, 18 to 60, with bipolar I or II disorder, euthymic 8 weeks or more, and comorbid OCD (YBOCS 15 or higher), all stable on lithium plus quetiapine (note: quetiapine 200 mg qhs also treats OCD in bipolar).
- Added memantine, titrated to 20 mg/day by week 3, or placebo, for 6 weeks.
- Primary outcome: change in YBOCS score.
Results
OCD symptoms fell more with memantine. YBOCS dropped from 20 to 13, versus 21 to 17 with placebo. That’s a very large effect size (2.0) by week 3, but outsized effects are common in small trials (due in part to publication bias and weaker methodology).
Mood symptoms stayed stable in both groups.
Side Effects
Nausea (9% vs 4%), dizziness, headache.
Limitations
Small; groups weren’t well matched on age.
Practice Implications
- Memantine is safer than many other options for OCD and already has evidence to improve cognition in bipolar.
- This study adds to a handful of other randomized trials supporting its use in OCD.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
