N-acetylcysteine
A building block of glutathione, the brain’s main antioxidant. Trials of it as an add-on in schizophrenia give mixed results.
At a glance
- Type
- Medicine: antioxidant
- Used for
- Tested as an add-on to antipsychotics, mainly for negative symptoms
- Status
- In trials
- Evidence
- EarlyHow evidence is rated
- Administration
- By mouth, added to an antipsychotic. In the trials, for 6 months to a year
- In Europe
- Part of the PsyCARE trial in France, which is recruiting
Clinical summaryFor health professionals
- Berk 2008 (Australia): 140 patients with chronic schizophrenia, 1 g twice a day for 24 weeks; PANSS total 6 points better than placebo, negative symptoms 1.8 points better.
- Conus 2018 (Switzerland): 63 patients with early psychosis, 2,700 mg a day for 6 months; no change in symptoms; processing speed improved; brain glutathione rose by 23%.
- Neill 2022 (Australia): 84 patients on clozapine with persistent symptoms, 2 g a day for up to 52 weeks; no effect on negative symptoms or cognition.
- Meta-analyses disagree: benefit only after 24 weeks or more (Yolland 2020, 7 trials); no difference (Zhang 2024, 8 trials, 594 patients).
- PsyCARE (France, 12 sites): 500 patients; NAC 2,400 mg a day or omega-3, assigned by biological profile. Recruiting.
What it is
N-acetylcysteine (NAC) is a building block of glutathione, the brain’s main antioxidant, which protects cells from damage by reactive oxygen. It also influences glutamate signalling and inflammation.1,2 It was tested as an add-on to antipsychotics, mainly for negative symptoms such as low motivation and withdrawal.
How well it works
In the first trial, in Australia, 140 people with long-standing schizophrenia took NAC or a placebo for six months. Symptoms improved by about 6 points more on NAC, mostly negative symptoms; hallucinations and delusions did not change.1 In a US trial of 60 people early in their illness, a year of NAC improved negative and disorganised symptoms.2
Other trials found less. In Lausanne, 63 people with early psychosis took NAC for six months. Their symptoms did not change, although their processing speed improved and glutathione in the brain rose by 23%.3 In Australia, 84 people whose symptoms persisted despite clozapine took NAC for up to a year, without effect on negative symptoms or thinking skills.4 In Germany, a trial in young people at high risk of psychosis stopped early because too few took part.5
Pooled analyses disagree. One, of seven trials, found benefits only after six months or more of treatment;6 another, of eight trials with 594 people, found no difference from placebo.7
Side effects
Across trials, side effects and dropping out were no more common on NAC than on placebo.4,7
Trials in Europe
The PsyCARE trial, at 12 hospitals in France, is recruiting 500 people. It assigns NAC or omega-3 fatty acids according to each person’s biological profile, to test whether matching the treatment to the person improves the results.8
Alternatives
Other medicines tested against inflammation or oxidative stress in schizophrenia include minocycline (opens in a new tab), celecoxib and aspirin (opens in a new tab) and omega-3 fatty acids (opens in a new tab). None is an established treatment.
What we don’t know yet
- Whether NAC helps people whose brain glutathione is low, as the Lausanne team proposed.
- How long it has to be taken to help.
