Nelson Siu Kei Lam1, Xin Xin Long2, Xuegang Li3, Mirette Saad4, Florence Lim5, James Cg Doery6, Robert C Griffin7, Cherrie Galletly8. 1. Faculty of Health and Sciences, The University of Adelaide, Adelaide, South Australia, Australia; Department of Psychiatry, Lyell McEwin Hospital, Elizabeth, South Australia, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia. Electronic address: nelson.lam@adelaide.edu.au. 2. Faculty of Health and Sciences, The University of Adelaide, Adelaide, South Australia, Australia. 3. Department of Rheumatology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. 4. Department of Pharmacy, Lyell McEwin Hospital, Elizabeth, South Australia, Australia. 5. National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs, Melbourne, Victoria, Australia. 6. Department of Medicine, Monash University, Clayton, Victoria, Australia; Department of Pathology, Monash Medical Centre, Clayton, Victoria, Australia. 7. Canberra Hospital, Woden Valley, Canberra, Australia. 8. Department of Medical Specialties, Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia; Ramsay Health Care (South Australia) Mental Health, South Australia, Australia; Northern Adelaide Local Health Network (NALHN), Adelaide, South Australia, Australia. Electronic address: cherrie.galletly@adelaide.edu.au.
Abstract
OBJECTIVES: To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. METHODS: A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605). DATA SOURCES: Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period. RESULTS: We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated. LIMITATION: Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English. CONCLUSION: Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.
OBJECTIVES: To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. METHODS: A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605). DATA SOURCES: Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period. RESULTS: We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated. LIMITATION: Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English. CONCLUSION: Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.