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

  • 2021-11-18
  • Pharmacopsychiatry 55(03)
    • Abdullah Al Maruf
    • Ethan A Poweleit
    • Lisa C Brown
    • Jeffrey R Strawn
    • Chad A Bousman

Study Design

Type
Meta-Analysis
Sample size
n = 707
Population
adults with MDD
Methods
Systematic review and meta-analysis following PRISMA recommendations; fixed- and random-effects meta-analysis and Cochrane Risk of Bias assessment

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.

Research Insights

  • L-Methylfolate→Improved Antidepressant Response

    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)

    Effect
    Beneficial
    Effect size
    Moderate
  • L-Methylfolate→Reduced Depression Symptoms

    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)

    Effect
    Beneficial
    Effect size
    Moderate
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