Abstract
Mitochondrial dysfunction has been implicated in the risk, pathophysiology, and progression of mood disorders, especially bipolar disorder (BD). Thus, the objective of this meta-analysis was to determine the overall antidepressant effect of mitochondrial modulators in the treatment of bipolar depression. Outcomes included improvement in depression scale scores, Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) score. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of diverse mitochondrial modulators were pooled to determine standard mean differences (SMDs) compared with placebo.13 RCTs were identified for qualitative review. The overall effect size of mitochondrial modulators on depressive symptoms was −0.48 (95% CI: −0.83 to −0.14, p = 0.007, I2 = 75%), indicative of a statistically significant moderate antidepressant effect. In the subgroup analysis, NAC improved depressive symptoms compared with placebo (−0.88, 95% CI: −1.48 to −0.27, I2 = 81%). In addition, there was no statistical difference between mitochondrial modulators and placebo in YMRS. Although mitochondrial modulators were superior to placebo in CGI-S score (−0.44, 95% CI: −0.83 to −0.06, I2 = 71%), only EPA was superior to placebo in subgroup analysis. Overall, a moderate antidepressant effect was observed for mitochondrial modulators compared with placebo in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
Highlights
Bipolar disorder (BD) is a common mood disorder characterized by alternating manic and depressive episodes [1]
There are N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), vitamin D, and melatonin exist for treating bipolar depression [4, 8]
Rating Scale (YMRS) scores, and Clinical Global Impression-Severity Scale (CGI-S) scores of mitochondrial modulators treatment versus placebo were used in the analysis
Summary
Bipolar disorder (BD) is a common mood disorder characterized by alternating manic and depressive episodes [1]. In the last few decades, substantial efforts have been made to evaluate the efficacy of mitochondrial modulators for the treatment of bipolar depression, both in monotherapy and as adjunctive treatment [9,10,11,12,13,14,15,16,17,18,19,20,21]. It remains unclear whether mitochondrial modulators has any benefit for the treatment of depressive symptoms in patients with mood disorders. Other mitochondrial regulators are controversial in the treatment of depressive symptoms
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