Wei Zheng1, Wen Li2, Han Qi3, Le Xiao3, Kang Sim4, Gabor S Ungvari5, Xiao-Bin Lu6, Xiong Huang6, Yu-Ping Ning6, Yu-Tao Xiang7. 1. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. Electronic address: zhengwei0702@163.com. 2. Unit of Psychiatry, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China; Center for Cognition and Brain Sciences, University of Macau, Macao SAR, China. 3. The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. 4. Institute of Mental Health, Buangkok Green Medical Park, Singapore. 5. The University of Notre Dame Australia, Fremantle, Australia; Division of Psychiatry, School of Medicine, University of Western Australia, Perth, Australia. 6. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. 7. Unit of Psychiatry, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China; Center for Cognition and Brain Sciences, University of Macau, Macao SAR, China. Electronic address: xyutly@gmail.com.or.
Abstract
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.
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.
Authors: Sabrina Mörkl; Linda Stell; Diana V Buhai; Melanie Schweinzer; Jolana Wagner-Skacel; Christian Vajda; Sonja Lackner; Susanne A Bengesser; Theresa Lahousen; Annamaria Painold; Andreas Oberascher; Josef M Tatschl; Matthäus Fellinger; Annabel Müller-Stierlin; Ana C Serban; Joseph Ben-Sheetrit; Ana-Marija Vejnovic; Mary I Butler; Vicent Balanzá-Martínez; Nikola Zaja; Polona Rus-Prelog; Robertas Strumila; Scott B Teasdale; Eva Z Reininghaus; Sandra J Holasek Journal: Nutrients Date: 2021-03-02 Impact factor: 5.717