The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study

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#acetylcysteine #adult #antidepressive-agents #bipolar-disorder #brief-psychiatric-rating-scale

The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study

Ellegaard et al., 2019 | J Affect Disord | Rct

Citation

Ellegaard Pernille Kempel, Licht Rasmus Wentzer, ... Nielsen Connie Thuroee. The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study. J Affect Disord. 2019-Feb-15;245:1043-1051. doi:10.1016/j.jad.2018.10.083

Abstract

OBJECTIVE: To investigate the efficacy of adjunctive N-acetylcysteine (NAC) for the treatment of acute bipolar depression. METHOD: A randomized, double-blind, multicentre, placebo-controlled trial including adult subjects diagnosed with bipolar disorder, currently experiencing a depressive episode. Participants were treated with 3 g/day NAC or placebo as an adjunctive to standard treatment for 20 weeks, followed by a 4-week washout where the blinding was maintained. The primary outcome was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) score over the 20-week treatment phase. Linear Mixed Effects Repeated Measures (LMERM) was used for analysing the primary outcome. RESULTS: A total of 80 subjects were included. The mean MADRS score at baseline was 30.1 and 28.8 in participants randomized to NAC and placebo, respectively. Regarding the primary outcome measure, the between-group difference (NAC vs. placebo) was 0.5, which was statistically non-significant (95% CI: -7.0-5.9;p = 0.88). All findings regarding secondary outcomes were statistically or clinically insignificant. LIMITATIONS: The study had a placebo response rate of 55.6% - high placebo response rates are associated with failure to separate from placebo. CONCLUSIONS: Based on our primary outcome measure, we could not confirm previous studies showing a therapeutic effect of adjunctive NAC treatment on acute bipolar depression. Further studies with larger samples are needed to elucidate if specific subgroups could benefit from adjunctive NAC treatment.

Key Findings

A total of 80 subjects were included. The mean MADRS score at baseline was 30.1 and 28.8 in participants randomized to NAC and placebo, respectively. Regarding the primary outcome measure, the between-group difference (NAC vs. placebo) was 0.5, which was statistically non-significant (95% CI: -7.0-5.9;p = 0.88). All findings regarding secondary outcomes were statistically or clinically insignificant.

Outcomes Measured

  • depression

Population

Field Value
Population See abstract
Sample Size 80
Age Range See abstract
Condition depression

MeSH Terms

  • Acetylcysteine
  • Adult
  • Antidepressive Agents
  • Bipolar Disorder
  • Brief Psychiatric Rating Scale
  • Depressive Disorder
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
  • Vertical: NAC-mental

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09