N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review an
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ORIGINAL INVESTIGATION
N-acetylcysteine as an adjunctive treatment for bipolar depression and major depressive disorder: a systematic review and meta-analysis of double-blind, randomized placebo-controlled trials Taro Kishi 1
&
Nobumi Miyake 2 & Makoto Okuya 1 & Kenji Sakuma 1 & Nakao Iwata 1
Received: 25 May 2020 / Accepted: 27 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 Nacetylcysteine 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 Nacetylcysteine 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. Keywords Depression . N-acetylcysteine . Depressive symptoms . CGI-S score . Gastrointestinal adverse events . Meta-analysis
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05629-2) contains supplementary material, which is available to authorized users. * Taro Kishi [email protected] 1
Department of Psychiatry, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
2
Department of Neuropsychiatry, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Ja
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