TY - JOUR
T1 - Mitochondrial modulators for obsessive–compulsive and related disorders
T2 - a systematic review and meta-analysis
AU - Kishi, Taro
AU - Sakuma, Kenji
AU - Iwata, Nakao
N1 - Funding Information:
The authors declare that there are no conflicts of interest in relation to this study. We declare the following interests within the past 3 years: TK, KS, and NI. TK has received speaker’s honoraria from Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, Yoshitomi, and Takeda; a Health Labor Sciences Research Grant, Japan Agency for Medical Research and Development grant, Grant-in-Aid for Scientific Research (C) grant, and a Fujita Health University School of Medicine research grant. KS has received speaker’s honoraria from Eisai, Kissei, Meiji, Otsuka, and Torii; a Fujita Health University School of Medicine research grant; Japan Agency for Medical Research and Development grant, and a Grant-in-Aid for Young Scientists (B) grant. NI has received speaker’s honoraria from Astellas, Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer and research grants from Daiichi Sankyo, Sumitomo, Meiji, and Otsuka.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive–compulsive and related disorders. Thus, in an attempt to answer this clinical question, we performed a systematic review and a random-effects meta-analysis of double-blind, randomized, placebo-controlled trials. The primary outcome was change in overall symptoms as measured using standardized rating scales. Other outcomes were response to treatment; improvement in anxiety-related scales scores, depression-related scale scores, Clinical Global Impression Severity Scale (CGI-S) scores, and Sheehan Disability Scale (SDS) scores; all-cause discontinuation; and individual adverse events. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. We reviewed 17 studies (n = 629, 72.62% female; duration = 2–20 weeks; mean age = 30.47 years) of MMs: eicosapentaenoic acid (K = 1), folic acid (K = 1), lithium (K = 1), N-acetylcysteine (K = 10), inositol (K = 3), and silymarin (K = 1). MMs outperformed placebo in overall improvement in symptoms (p < 0.01) and in improving anxiety-related scale scores (p = 0.05). Subgroup analysis of individual MMs revealed that although overall symptoms were better improved by N-acetylcysteine (p < 0.01) and lithium (p = 0.04), no MMs outperformed placebo in terms of improving anxiety-related scale scores. Neither pooled nor individual MMs outperformed placebo in improving response to treatment, depression-related scale scores, CGI-S scores, SDS scores, or all-cause discontinuation. N-acetylcysteine was no more associated with a higher incidence of individual adverse events including gastrointestinal symptoms, than placebo. In conclusion, N-acetylcysteine was beneficial in the treatment of obsessive–compulsive and related disorders. However, further study with larger samples is necessary to confirm this finding.
AB - It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive–compulsive and related disorders. Thus, in an attempt to answer this clinical question, we performed a systematic review and a random-effects meta-analysis of double-blind, randomized, placebo-controlled trials. The primary outcome was change in overall symptoms as measured using standardized rating scales. Other outcomes were response to treatment; improvement in anxiety-related scales scores, depression-related scale scores, Clinical Global Impression Severity Scale (CGI-S) scores, and Sheehan Disability Scale (SDS) scores; all-cause discontinuation; and individual adverse events. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. We reviewed 17 studies (n = 629, 72.62% female; duration = 2–20 weeks; mean age = 30.47 years) of MMs: eicosapentaenoic acid (K = 1), folic acid (K = 1), lithium (K = 1), N-acetylcysteine (K = 10), inositol (K = 3), and silymarin (K = 1). MMs outperformed placebo in overall improvement in symptoms (p < 0.01) and in improving anxiety-related scale scores (p = 0.05). Subgroup analysis of individual MMs revealed that although overall symptoms were better improved by N-acetylcysteine (p < 0.01) and lithium (p = 0.04), no MMs outperformed placebo in terms of improving anxiety-related scale scores. Neither pooled nor individual MMs outperformed placebo in improving response to treatment, depression-related scale scores, CGI-S scores, SDS scores, or all-cause discontinuation. N-acetylcysteine was no more associated with a higher incidence of individual adverse events including gastrointestinal symptoms, than placebo. In conclusion, N-acetylcysteine was beneficial in the treatment of obsessive–compulsive and related disorders. However, further study with larger samples is necessary to confirm this finding.
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U2 - 10.1038/s41398-022-02026-5
DO - 10.1038/s41398-022-02026-5
M3 - Article
C2 - 35764619
AN - SCOPUS:85132968004
VL - 12
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 263
ER -