Adjunctive folate for major mental disorders: A systematic review

Objectives: This is a meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of adjunctive folate for three major mental disorders (schizophrenia, bipolar disorder, and major depressive disorder (MDD)). Methods: Review Manager Program Version 5.3 was used to analyze data. Results: Fourteen studies with 16 RCTs (n = 1,520) on folate for schizophrenia (4 RCTs, n = 210), mood disorders (i.e., unipolar and bipolar depression) (1 RCT, n = 60), bipolar disorder (2 RCTs, n = 189) and MDD (9 RCTs, n = 1,061) were analyzed separately by diagnosis. For schizophrenia, adjunctive folate was not superior to placebo in terms of total psychopathology (standardized mean difference (SMD) = −0.14, 95% confidential interval (CI): −0.67, 0.39; I² = 30%, P = 0.60), and positive (SMD = 0.09, 95% CI: -0.44, 0.62; I² = not applicable, P = 0.74), negative (SMD = −0.39, 95% CI:−0.84, 0.05; I² = 50%, P = 0.08), and general symptom scores (SMD = −0.33, 95%CI:−0.87, 0.20; I² = not applicable, P = 0.22). For bipolar and unipolar depression, adjunctive folate was significantly superior to placebo in improving depressive symptoms. For bipolar disorder, adjunctive folate was effective in treating the acute phase of mania in bipolar disorder, but not in the acute phase of depression. For MDD, adjunctive folate was significantly superior to placebo in improving depressive symptoms (SMD = −0.38, 95%CI: −0.66, −0.09; I² = 71%, P = 0.01), which was confirmed in 5 of the 10 subgroups. Discontinuation due to any reason and adverse drug reactions were similar between folate and placebo in each diagnostic category. Conclusion: This systematic review found adjunctive folate appeared to be effective and safe for MDD and bipolar manic episode, but it was not effective in treating schizophrenia.