TY - JOUR
T1 - The efficacy of adjunctive N-acetylcysteine in acute bipolar depression
T2 - A randomized placebo-controlled study
AU - Ellegaard, Pernille Kempel
AU - Licht, Rasmus Wentzer
AU - Nielsen, René Ernst
AU - Dean, Olivia May
AU - Berk, Michael
AU - Poulsen, Henrik Enghusen
AU - Mohebbi, Mohammadreza
AU - Nielsen, Connie Thuroee
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Bipolar disorder
KW - Depression
KW - Glutathione
KW - N acetylcysteine
KW - Treatment
U2 - 10.1016/j.jad.2018.10.083
DO - 10.1016/j.jad.2018.10.083
M3 - Journal article
C2 - 30699846
AN - SCOPUS:85057810042
SN - 0165-0327
VL - 245
SP - 1043
EP - 1051
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -