Adjunctive folate for major mental disorders: A systematic review
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; I 2 = 30%, P = 0.60), and positive (SMD = 0.09, 95% CI: -0.44, 0.62; I 2 = not applicable, P = 0.74), negative (SMD = -0.39, 95% CI:-0.84, 0.05; I 2 = 50%, P = 0.08), and general symptom scores (SMD = -0.33, 95%CI:-0.87, 0.20; I 2 = 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; I 2 = 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.
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Vitamin B9 supplements together with traditional treatment of bipolar disorder appear more effective than placebo.
“Vitamin B9 supplements together with the traditional treatment of bipolar disorder appear to be more effective than the placebo effect (Zheng et al. 2020).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Zheng et al. 2020
3 mg of folate supplements (along with sodium valproate) are effective in treating the acute phase of bipolar disorder.
“3 mg of folate supplements were effective (along with sodium valproate) in the treatment of the acute phase of bipolar disorder.”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Zheng et al. 2020
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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- Authors
- Zheng, W., Li, W., Qi, H., Xiao, L., Sim, K., Ungvari, G. S., Lu, X.-B., Huang, X., Ning, Y.-P., & Xiang, Y.-T.
- Affiliations
- Guangzhou Medical University (CN)
- University of Macau (MO)
- Capital Medical University (CN)
- Institute of Mental Health (SG)
- The University of Western Australia (AU)
- Corresponding author
- Zheng, Wei
- Xiang, Yu-Tao
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 267
- Pages
- 123-130
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W3001918796
- Cited by
- 37
- References
- 57
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 2
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- folic acid, adjunctive therapy, schizophrenia, bipolar disorder, major depressive disorder, bipolar depression, mania, depressive symptoms, psychopathology, treatment efficacy, adverse drug reactions, vitamin supplementation, mood disorders
- MeSH terms
- Bipolar Disorder, Depressive Disorder, Major, Major Depressive Disorder, Folic Acid, Humans, Schizophrenia, Antipsychotic Agents
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