Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.
BACKGROUND
N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.


METHODS
The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.


RESULTS
There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.


CONCLUSIONS
There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations.


BACKGROUND
The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).
Deakin University, School of Medicine, Barwon Health, P.O. Box 291, Geelong, 3220, Australia. mikebe@barwonhealth.org.au
Michael
M
Berk
Olivia M
OM
Dean
Sue M
SM
Cotton
Clarissa S
CS
Gama
Flavio
F
Kapczinski
Brisa
B
Fernandes
Kristy
K
Kohlmann
Susan
S
Jeavons
Karen
K
Hewitt
Kirsteen
K
Moss
Christine
C
Allwang
Ian
I
Schapkaitz
Heidi
H
Cobb
Ashley I
AI
Bush
Seetal
S
Dodd
Gin S
GS
Malhi
D000111:Acetylcysteine / Q000008:administration & dosage*; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001714:Bipolar Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D010919:Placebos / Q000008:administration & dosage; D011788:Quality of Life; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010919:Placebos; D000111:Acetylcysteine