Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis

• Published in: Complementary therapies in medicine 2021-09, Vol.61, p.102770-102770, Article 102770
• Main Authors: Altaf, Rabail, Gonzalez, Irasema, Rubino, Kimberley, Nemec, Eric C.
• Format: Article
• Language: English
• Subjects: Antidepressants; Bias; Bipolar disorder; Clinical trials; Confidence intervals; COVID-19; Folate; Folic acid; Inhibitors; l-methylfolate; Literature reviews; Major depressive disorder; Mental depression; Mental disorders; Meta-analysis; Mutation; Norepinephrine; Patients; Psychotropic drugs; Remission; Remission (Medicine); Schizophrenia; Search engines; Serotonin; Serotonin uptake inhibitors; SNRI; SSRI; Systematic review; Therapy; Vitamin B
• ISSN: 0965-2299; 1873-6963
• DOI: 10.1016/j.ctim.2021.102770

•Folate has been linked with the synthesis of monoamines which play an essential role in symptoms of depression.•Folate deficiency has been associated with depression.•The study aimed to evaluate the efficacy of folic acid or l-methylfolate as an adjunct therapy for depression treatment.•Folate, as an adjunct to SSRI/SNRIs improves depression scale scores, patient remission, and response rates. 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. 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. 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 ≤ 0.00001]; 6 week: [SMD = –0.94 (95 % CI: –1.85 to -0.03) P = 0.04]; ≥ 8 week: [SMD= -0.57 (95 % CI: -0.91 to -0.23) P = 0.0009]. Adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates.