NAC for OCD and Anxiety: What the Trials Show (A Promising Start, Then a Negative 20-Week Trial)
NAC is a glutamate modulator that psychiatrists have tried as an add-on for OCD and hair pulling. Early trials were encouraging, the largest OCD trial was negative, and the anxiety evidence is thinner than the internet suggests.
By Kymata Health Editorial Published Last checked
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Key takeaways
From 8 sources- In OCD, NAC has been tested as an add-on to SSRI medicines: a 2024 meta-analysis of 6 trials (195 patients) found a borderline benefit at 5 to 8 weeks (p = 0.05) and none at shorter durations or beyond 12 weeks1.
- The largest single trial gave 98 adults 2 to 4 g a day for 20 weeks and found no benefit over placebo on OCD, anxiety or depression scores3.
- Hair pulling is where NAC looked best: 56% of adults were much or very much improved on NAC versus 16% on placebo4. A similar trial in children found no difference (25% vs 21% responders)5.
- For anxiety itself, a 2022 meta-analysis of trials in OCD and related disorders found NAC did not beat placebo on anxiety rating scales2.
- NAC was well tolerated across these trials, with mainly mild stomach upset31.
What this article covers
1 evidence profileThe evidence, graded
Pulled from the trial tables in our evidence profiles. Grades follow our evidence-grading policy.
Graded findings
1 row- CGrade CSymptom scores when added to standard psychiatric careMixed Adjunctive NAC improved total psychopathology scores in schizophrenia (SMD -0.74, I² 84%) but had no significant effect in bipolar disorder and only a small effect on major depressive symptoms. Adverse reactions and dropouts were similar to control.NAC (N-acetylcysteine) · Meta-analysis · n=701 · 2018 · PMID 29457216
Why psychiatrists tried NAC
NAC is used in medicine for lung conditions and as an antidote, but it also appears to act on glutamate levels in a brain region tied to compulsive behaviour4. That made it a candidate add-on for people with OCD who do not respond fully to SSRIs1.
Across major mental disorders, a 2018 meta-analysis of 6 trials (701 patients) found add-on NAC improved overall symptoms in schizophrenia (SMD −0.74), had no significant effect in bipolar disorder and only a small effect in major depression6. No anxiety-disorder trials were part of that analysis6.
OCD: early promise, then a large negative trial
The 2024 meta-analysis pooled 6 randomized trials (195 patients) of NAC added to SSRIs for moderate to severe OCD1. Total Y-BOCS scores favoured NAC only in trials lasting 5 to 8 weeks, and obsession and compulsion subscores did not differ1.
A broader 2022 meta-analysis of 17 trials (629 participants) in OCD and related disorders, 10 of them testing NAC, found NAC improved overall symptoms more than placebo (p < 0.01)2. It did not improve response rates, depression scores or disability2.
The trial that carries the most weight is the Australian phase III study: 98 adults with OCD took 2 to 4 g a day or placebo for 20 weeks, and NAC showed no advantage on the Y-BOCS (mean difference 0.53, favouring placebo) or on any secondary measure3.
Hair pulling and skin picking
In a 12-week trial of 50 adults with trichotillomania, NAC at 1,200 to 2,400 mg a day reduced hair-pulling scores more than placebo, and 56% were much or very much improved versus 16%4. Improvement first showed up after 9 weeks4.
A 12-week add-on trial in 39 children and teens found no difference from placebo on any measure; 25% responded on NAC and 21% on placebo5. Its authors advised behavioural therapy first for children5.
What about anxiety?
The evidence for NAC in anxiety comes mostly from secondary outcomes in OCD trials. In the 2022 meta-analysis, no individual compound, NAC included, beat placebo on anxiety rating scales2, and the 20-week OCD trial saw no anxiety benefit3.
Searches for 'NAC for anxiety' often lead to glutathione and antioxidant claims; see NAC and glutathione (GlyNAC) for what those trials measured. For anxiety supplements with more direct trial data, compare L-theanine.
Who paid for the research
The negative 20-week OCD trial was funded by an Australian NHMRC project grant (GNT1104460), which had no role in the analysis3. The adult hair-pulling trial's lead author disclosed research grants from the National Institute of Mental Health, Forest Pharmaceuticals, GlaxoSmithKline and Somaxon Pharmaceuticals and consulting for Pfizer and Somaxon4. The paediatric trial was supported by NIH grants5.
The 2024 meta-analysis authors declared no commercial or financial conflicts1. The 2022 meta-analysis authors reported no conflicts related to the study, though its lead author disclosed speaker fees from several drugmakers2.
Who should be careful
Nitrates: in a trial of 46 patients with severe unstable angina, intravenous NAC 5 g every 6 hours added to intravenous nitroglycerin caused symptomatic low blood pressure in 7 of 24 patients versus none of 22 on nitroglycerin alone7. Anyone on nitrate medicines should check with their prescriber first, and you can run other medicines through the interaction checker.
Psychiatric care: every OCD trial above tested NAC alongside prescribed treatment, not instead of it, so stopping an SSRI to try NAC has no trial support13. NAC also has an unusual regulatory status: FDA approved it as a drug in 1963 and says it intends not to act against NAC sold as a supplement unless the product makes disease claims8. More in is NAC safe to take daily?
Quick answers
Common questions
4 answersDoes NAC help OCD?
How much NAC was used in OCD and hair-pulling trials?
Does NAC help anxiety?
How long does NAC take to work for hair pulling?
In the adult trial, improvement first separated from placebo after 9 weeks of a 12-week course4.
Keep reading
Full evidence profiles
Every graded study, studied doses, interactions and safetyRelated articles
4 articles- ArticleIs NAC Safe to Take Daily? What Long Trials and FDA's 2022 Policy SayIs NAC safe to take daily?
- ArticleNAC and Glutathione: What GlyNAC Trials Actually MeasuredDoes NAC raise glutathione, and what is GlyNAC?
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References
8 sources. Numbers in the text link here.
Sources cited in this article
8 sources- 1The safety and efficacy of N-acetylcysteine as an augmentation in the treatment of obsessive-compulsive disorder in adults: a systematic review and meta-analysis of randomized clinical trialsFrontiers in Psychiatry, 2024 · PMID 39376972
- 2Mitochondrial modulators for obsessive-compulsive and related disorders: a systematic review and meta-analysisTranslational Psychiatry, 2022 · PMID 35764619
- 3N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trialProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2022 · PMID 35304155
- 4N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled studyArchives of General Psychiatry, 2009 · PMID 19581567
- 5N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trialJournal of the American Academy of Child and Adolescent Psychiatry, 2013 · PMID 23452680
- 6N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trialsActa Psychiatrica Scandinavica, 2018 · PMID 29457216
- 7Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectorisCirculation, 1988 · PMID 3127076
- 8Guidance for Industry: Policy Regarding N-acetyl-L-cysteine (archived copy)U.S. Food and Drug Administration, 2022
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