Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis

source extracted confidence: high 2026-04-09
#humans #dietary-supplements #depressive-disorder #antidepressive-agents #treatment-outcome

Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis

Cheng et al., 2025 | Psychol Med | Systematic Review

Citation

Cheng Ying-Chih, Huang Wei-Lieh, ... Tu Yu-Kang. Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis. Psychol Med. 2025-May-02;55:e134. doi:10.1017/S0033291725000996

Abstract

BACKGROUND: Nutraceuticals have been taken as an alternative and add-on treatment for depressive disorders. Direct comparisons between different nutraceuticals and between nutraceuticals and placebo or antidepressants are limited. Thus, it is unclear which nutraceuticals are the most efficacious. METHODS: We conducted a network meta-analysis to estimate the comparative efficacy and tolerability of nutraceuticals for the treatment of depressive disorder in adults. The primary outcome was the change in depressive symptoms, as measured by the standard mean difference (SMD). Secondary outcomes included response rate, remission rate, and anxiety. Tolerability was defined as all-cause discontinuation and adverse events. Frequentist random-effect NMA was conducted. RESULTS: Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion. Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response. Notable combinations were Eicosapentaenoic acid + Docosahexaenoic Acid plus ADT (EPA + DHA + ADT) (SMD 1.04, 95% confidence interval 0.64-1.44), S-Adenosyl Methionine (SAMe) + ADT (0.99, 0.31-1.68), curcumin + ADT (1.03, 0.55-1.51), Zinc + ADT (1.59, 0.63-2.55), tryptophan + ADT (1.24, 0.32-2.16), and folate + ADT (0.64, 0.17-1.10). Additionally, four nutraceutical monotherapies demonstrated superior efficacy compared to ADT: EPA + DHA (0.6, 0.32-0.88), SAMe (0.52, 0.18-0.87), curcumin (0.62, -0.17 to 1.40) and saffron (0.69, 0.34-1.04). It is noted that EPA + DHA, SAMe, and curcumin showed strong performance as either monotherapies or adjuncts to ADT. Most nutraceuticals showed comparable tolerability to placebo. CONCLUSIONS: This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.

Key Findings

Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion. Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response. Notable combinations were Eicosapentaenoic acid + Docosahexaenoic Acid plus ADT (EPA + DHA + ADT) (SMD 1.04, 95% confidence interval 0.64-1.44), S-Adenosyl Methionine (SAMe) + ADT (0.99, 0.31-1.68), curcumin + ADT (1.03, 0.55-1.51), Zinc + ADT (1

Outcomes Measured

  • anxiety

Population

Field Value
Population See abstract
Sample Size 17437
Age Range See abstract
Condition anxiety

MeSH Terms

  • Humans
  • Dietary Supplements
  • Depressive Disorder
  • Antidepressive Agents
  • Treatment Outcome

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review, Comparative Study, Network Meta-Analysis
  • Vertical: folate

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09