Adding N-acetylcysteine to sertraline eases obsessions faster
STUDY: Askari S et al, Communications Medicine 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Iran University of Medical Sciences
Background
N-acetylcysteine (NAC) seemed like a viable choice for OCD. It helped other compulsive disorders like trichotillomania, and modulates the glutamatergic cortico-striatal hyperactivity that drives intrusive thoughts. Unfortunately, the trials are inconclusive, which means there’s a need for further research like this.
The Study
- 35 adults with moderate-to-severe OCD, medication-free for at least six weeks prior to enrollment
- Randomized to sertraline 200 mg/day plus NAC 2400 mg/day or sertraline plus placebo for 12 weeks
- Double-blind; OCD severity assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), a clinician-rated measure of obsession and compulsion severity
Results
This small trial was positive on its primary outcome (time-treatment interaction on reduction in Y-BOCS scores), but only for obsessions, not compulsions. NAC brought faster response, with greater obsession score reductions at weeks 4, 8, and 12, with the largest gap at week 8. Compulsion scores improved equally in both groups.
Response rates significantly greater in NAC group (p = 0.004; but still similar:100% in the NAC group versus 92.6% in the placebo group). Both groups improved on attention and processing speed, but NAC added no cognitive benefit beyond what sertraline alone produced.
Side Effects
Side effects were mild and comparable between groups: decreased libido, reduced appetite, and occasional headache or stomach upset. No one stopped treatment because of side effects.
Limitations
Only 35 patients, nearly all women, in a single Iranian center. The 26% dropout rate is notable. Both groups had unusually high response rates, which may have obscured a larger NAC benefit.
Practice Implications
- NAC 1200 mg bid speeded response, but didn’t change the bottom line or response in this trial.
- Overall, this supplement doesn’t have a strong signal in OCD. More research is needed. If using NAC, here are products that were tested by independent labs.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
