TY - JOUR AU - Maruf, Abdullah Al; Poweleit, Ethan A.; Brown, Lisa C.; Strawn, Jeffrey R.; Bousman, Chad A. TI - Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders SN - 0176-3679 SN - 1439-0795 PY - 2021 JO - Pharmacopsychiatry JF - Pharmacopsychiatry LA - EN VL - 55 IS - 03 SP - 139 EP - 147 DA - 2021/11/18 KW - L-methylfolate KW - depression KW - adjunct therapy AB - Objectives  Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including adjunctive L-methylfolate. Given that L-methylfolate augmentation is rarely included in major clinical practice guidelines, we sought to systematically review evidence for L-methylfolate augmentation in adults with MDD and to examine its efficacy meta-analytically.Methods  We systematically searched PubMed for articles up to December 31, 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Included studies were published in peer-reviewed, English-language journals and examined L-methylfolate adjunctive therapy in depressive disorders or its effect on antidepressant response. A fixed- and random-effects meta-analysis and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted.Results  Qualitative assessment of nine articles (N=6,707 patients) suggests that adjunctive L-methylfolate improved antidepressant response. In the meta-analysis of categorical Hamilton Rating Scale for Depression-17 response, (three studies, N=483) adjunctive L-methylfolate was associated with a small effect versus antidepressant monotherapy (relative risk: 1.25, 95% confidence interval [CI]=1.08 to 1.46, p=0.004). A meta-analysis of four studies (N=507) using a continuous measure of depressive symptoms showed a similar effect of adjunctive L-methylfolate (standardized mean difference=− 0.38, 95% CI=− 0.59 to−0.17, p=0.0003).Conclusion  Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with MDD. PB - Georg Thieme Verlag KG DO - 10.1055/a-1681-2047 UR - http://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1681-2047 ER -