Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in
                    Depressive Disorders

Abdullah Al Maruf; Ethan A. Poweleit; Lisa C. Brown; Jeffrey R. Strawn; Chad A. Bousman

doi:10.1055/a-1681-2047

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2022; 55(03): 139-147
DOI: 10.1055/a-1681-2047

Review

Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders

Abdullah Al Maruf‡

¹College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Manitoba, Canada

²Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada

³Departments of Psychiatry and Physiology & Pharmacology, University of Calgary, Alberta, Canada

,

Ethan A. Poweleit‡

⁴Divisions of Biomedical Informatics, Clinical Pharmacology & Research in Patient Services, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

⁵Department of Biomedical Informatics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA

,

Lisa C. Brown

⁶Tempus Labs, Chicago, IL, USA

,

Jeffrey R. Strawn

⁷Departments of Psychiatry and Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA

,

Chad A. Bousman

²Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada

⁸Department of Medical Genetics, University of Calgary, Alberta, Canada

⁹Department of Community Health Sciences, University of Calgary, Alberta, Canada

¹⁰Alberta Children’s Hospital Research Institute, University of Calgary, Alberta, Canada

› Author Affiliations

Abstract

Objectives Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including adjunctive L-methylfolate. Given that L-methylfolate augmentation is rarely included in major clinical practice guidelines, we sought to systematically review evidence for L-methylfolate augmentation in adults with MDD and to examine its efficacy meta-analytically.

Methods We systematically searched PubMed for articles up to December 31, 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Included studies were published in peer-reviewed, English-language journals and examined L-methylfolate adjunctive therapy in depressive disorders or its effect on antidepressant response. A fixed- and random-effects meta-analysis and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted.

Results Qualitative assessment of nine articles (N=6,707 patients) suggests that adjunctive L-methylfolate improved antidepressant response. In the meta-analysis of categorical Hamilton Rating Scale for Depression-17 response, (three studies, N=483) adjunctive L-methylfolate was associated with a small effect versus antidepressant monotherapy (relative risk: 1.25, 95% confidence interval [CI]=1.08 to 1.46, p=0.004). A meta-analysis of four studies (N=507) using a continuous measure of depressive symptoms showed a similar effect of adjunctive L-methylfolate (standardized mean difference=− 0.38, 95% CI=− 0.59 to−0.17, p=0.0003).

Conclusion Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with MDD.

Key words

L-methylfolate - depression - adjunct therapy

Full Text

References

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