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N-acetyl cysteine for depressive symptoms in bipolar disorder - a double blind, randomized, placebo-controlled trial

journal contribution
posted on 2008-09-15, 00:00 authored by Michael BerkMichael Berk, D Copolov, Olivia DeanOlivia Dean, K Lu, S Jeavons, I Schapkaitz, Murray Anderson-Hunt, A Bush
Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorderare complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder.

Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning.

Results: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: 8.05 [13.16, 2.95], p .002) a n d most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p .968) and no significant between-group differences inadverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts.

Conclusions:
NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar  disorder.

History

Journal

Biological psychiatry

Volume

64

Issue

6

Pagination

468 - 475

Publisher

Elsevier

Location

Philadelphia, Pa.

ISSN

0006-3223

eISSN

1873-2402

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2008 Society of Biological Psychiatry