TY - JOUR
T1 - N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder
T2 - a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials
AU - Kishi, Taro
AU - Miyake, Nobumi
AU - Okuya, Makoto
AU - Sakuma, Kenji
AU - Iwata, Nakao
N1 - Funding Information:
Dr. Iwata has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer and has had research grants from Daiichi Sankyo, Dainippon Sumitomo, Meiji, and Otsuka.
Funding Information:
Dr. Sakuma has received speaker’s honoraria from Eisai, Kissei, Meiji, Otsuka, and Torii and has received a Fujita Health University School of Medicine research grant as well as a Grant-in-Aid for Young Scientists (B).
Funding Information:
Dr. Kishi has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, Yoshitomi, and Tanabe-Mitsubishi and has received a Health Labour Sciences Research Grant, Grant-in-Aid for Scientific Research (C), and a Fujita Health University School of Medicine research grant.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Rationale: It remains unclear whether using N-acetylcysteine as an adjunctive treatment has any benefit for bipolar depression and major depressive disorder. Objectives: A systematic review and random-effect meta-analysis of double-blind, randomized placebo-controlled trials was conducted to explore the clinical question. Methods: Outcomes included improvement in depression scale scores (primary), Young Mania Rating Scale score, Hamilton Anxiety Rating Scale score, Clinical Global Impression-Severity Scale (CGI-S) score, Global Assessment of Functioning Scale score, Social and Occupational Functioning Assessment Scale score, Range of Impaired Functioning Tool score, Streamed Longitudinal Interval Clinical Evaluation for the Longitudinal Interview Follow-Up Evaluation score, quality of life scales scores, and the incidence of all-cause discontinuation and individual adverse events. Results: Seven studies (n = 728, 8–24 weeks, mean age = 46.81, % female = 58.45%) were included. N-acetylcysteine did not improve depressive symptoms compared with placebo (N = 7, n = 579, standardized mean difference (SMD) = − 0.12, 95% confidence interval (95% CI) = − 0.38, 0.14, p = 0.38, I2 = 52.74%). The meta-regression analysis detected an association between effect size and publication year (coefficient = 0.06, 95% CI = 0.00, 0.11, p = 0.04, I2 = 27.56%). Although N-acetylcysteine was superior to placebo in CGI-S score (N = 6, n = 563, SMD = − 0.28, 95% CI = − 0.47, − 0.10, p < 0.01, I2 = 14.88%), there was no significant difference in the other efficacy outcomes between the treatment groups. Although N-acetylcysteine was associated with a higher incidence of gastrointestinal adverse events compared with placebo (N = 4, n = 537, risk ratio = 1.79, 95% CI = 1.37, 2.32, p < 0.01, I2 = 0.00%, number needed to treat to harm = 7), there was no significant difference in all-cause discontinuation and other safety outcomes between the treatments. Conclusions: Although N-acetylcysteine decreased CGI-S score, no specific improvements in symptoms were identified.
AB - Rationale: It remains unclear whether using N-acetylcysteine as an adjunctive treatment has any benefit for bipolar depression and major depressive disorder. Objectives: A systematic review and random-effect meta-analysis of double-blind, randomized placebo-controlled trials was conducted to explore the clinical question. Methods: Outcomes included improvement in depression scale scores (primary), Young Mania Rating Scale score, Hamilton Anxiety Rating Scale score, Clinical Global Impression-Severity Scale (CGI-S) score, Global Assessment of Functioning Scale score, Social and Occupational Functioning Assessment Scale score, Range of Impaired Functioning Tool score, Streamed Longitudinal Interval Clinical Evaluation for the Longitudinal Interview Follow-Up Evaluation score, quality of life scales scores, and the incidence of all-cause discontinuation and individual adverse events. Results: Seven studies (n = 728, 8–24 weeks, mean age = 46.81, % female = 58.45%) were included. N-acetylcysteine did not improve depressive symptoms compared with placebo (N = 7, n = 579, standardized mean difference (SMD) = − 0.12, 95% confidence interval (95% CI) = − 0.38, 0.14, p = 0.38, I2 = 52.74%). The meta-regression analysis detected an association between effect size and publication year (coefficient = 0.06, 95% CI = 0.00, 0.11, p = 0.04, I2 = 27.56%). Although N-acetylcysteine was superior to placebo in CGI-S score (N = 6, n = 563, SMD = − 0.28, 95% CI = − 0.47, − 0.10, p < 0.01, I2 = 14.88%), there was no significant difference in the other efficacy outcomes between the treatment groups. Although N-acetylcysteine was associated with a higher incidence of gastrointestinal adverse events compared with placebo (N = 4, n = 537, risk ratio = 1.79, 95% CI = 1.37, 2.32, p < 0.01, I2 = 0.00%, number needed to treat to harm = 7), there was no significant difference in all-cause discontinuation and other safety outcomes between the treatments. Conclusions: Although N-acetylcysteine decreased CGI-S score, no specific improvements in symptoms were identified.
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U2 - 10.1007/s00213-020-05629-2
DO - 10.1007/s00213-020-05629-2
M3 - Article
C2 - 32767039
AN - SCOPUS:85089097190
VL - 237
SP - 3481
EP - 3487
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 11
ER -