PMID- 34450256 OWN - NLM STAT- MEDLINE DCOM- 20211124 LR - 20221207 IS - 1873-6963 (Electronic) IS - 0965-2299 (Linking) VI - 61 DP - 2021 Sep TI - Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis. PG - 102770 LID - S0965-2299(21)00111-4 [pii] LID - 10.1016/j.ctim.2021.102770 [doi] AB - OBJECTIVE: Evaluate depression scores, response, and remission rates in patients with major depression receiving adjunct therapy with folate (L-Methylfolate or folic acid) compared to selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (SSRI or SNRI) monotherapy. METHODS: Academic Search Premier, CINAHL Complete, Cochrane Database of Systematic Reviews, Medline with Full Text, PsychInfo, PubMed, ClinicalTrials.org, and Google Scholar were searched utilizing specific key words. Identified studies were independently screened for inclusion by two reviewers, were assessed for risk of bias using the Revised Cochrane risk-of-bias tool (RoB2), then meta-analyzed using a random effects model with Review Manager (5.4) software. RESULTS: The initial search revealed 293 articles with 6 randomized control trials ultimately meeting inclusion criteria. In patients with depression, analysis of 5 studies revealed a significantly lower Hamilton Depression Rating Scale (HAM-D) score in individuals treated with adjunct therapy with l-Methylfolate/folic acid [Mean Difference (MD): -2.16 (95 % CI -3.62 to -0.69), p = 0.004], as well a combined HAM-D and Beck Depression Inventory-II (BDI-II) scores [standardized mean difference (SMD): -0.61 (95 % Confidence Interval CI -0.97 to -0.24), p = 0.002]. This adjunct therapy also yielded an improved response rate [Risk Ratio (RR): 1.36 (95 % CI: 1.16-1.59) P = 0.0001], increase in remission rate [RR: 1.39 (95 % CI: 1.00-1.92) P = 0.05], and reduction in depression scores after varying durations of treatment, 4 week: [SMD = -0.38 (95 % CI: -0.55 to -0.22) P /= 8 week: [SMD= -0.57 (95 % CI: -0.91 to -0.23) P = 0.0009]. CONCLUSION: Adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Altaf, Rabail AU - Altaf R AD - Department of Physician Assistant Studies, 5151 Park Ave, Sacred Heart University, Fairfield, CT, 06825, United States. Electronic address: altafr@mail.sacredheart.edu. FAU - Gonzalez, Irasema AU - Gonzalez I AD - Department of Physician Assistant Studies, 5151 Park Ave, Sacred Heart University, Fairfield, CT, 06825, United States. Electronic address: gonzalezi5@mail.sacredheart.edu. FAU - Rubino, Kimberley AU - Rubino K AD - Psychiatry Department, Contemporary Care-Greenwich, 81 Holly Hill Ln, Greenwich, CT, 06830, United States. Electronic address: kimberlyr@contemporarycare.net. FAU - Nemec, Eric C 2nd AU - Nemec EC 2nd AD - Department of Physician Assistant Studies, 5151 Park Ave, Sacred Heart University, Fairfield, CT, 06825, United States. Electronic address: nemece@sacredheart.edu. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20210824 PL - Scotland TA - Complement Ther Med JT - Complementary therapies in medicine JID - 9308777 RN - 0 (Serotonin Uptake Inhibitors) RN - 0 (Serotonin and Noradrenaline Reuptake Inhibitors) RN - 935E97BOY8 (Folic Acid) SB - IM MH - *Depressive Disorder, Major/drug therapy MH - Folic Acid MH - Humans MH - Selective Serotonin Reuptake Inhibitors/therapeutic use MH - *Serotonin and Noradrenaline Reuptake Inhibitors OTO - NOTNLM OT - Folate OT - Folic acid OT - Major depressive disorder OT - SNRI OT - SSRI OT - l-methylfolate EDAT- 2021/08/28 06:00 MHDA- 2021/11/25 06:00 CRDT- 2021/08/27 20:14 PHST- 2020/08/29 00:00 [received] PHST- 2021/07/14 00:00 [revised] PHST- 2021/08/18 00:00 [accepted] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/11/25 06:00 [medline] PHST- 2021/08/27 20:14 [entrez] AID - S0965-2299(21)00111-4 [pii] AID - 10.1016/j.ctim.2021.102770 [doi] PST - ppublish SO - Complement Ther Med. 2021 Sep;61:102770. doi: 10.1016/j.ctim.2021.102770. Epub 2021 Aug 24.