Nutraceuticals and phytoceuticals for the treatment of major depressive disorder: a systematic review and network meta-analysis.

In 30 seconds

This systematic review and network meta-analysis assessed randomized trials of nutraceuticals and phytoceuticals for major depressive disorder, comparing them with placebo or treatment as usual. Across 163 studies involving 15,757 participants, analyses restricted to compounds with at least two trials and other quality filters found lower depressive symptom scores versus placebo with EPA (SMD = -1.67;95%C.I. = -2.38;-0.97), vitamin D3, and St. John’s wort extract ZE117. However, heterogeneity and inconsistency were substantial, and confidence in the evidence was low to very low; the authors concluded that only a few compounds showed potential after filtering lower-quality evidence.

Key findings

• For depressive symptoms, EPA versus placebo had SMD = -1.67;95%C.I. = -2.38;-0.97 in filtered analyses (k = 20, n = 8483).
• Vitamin D3 and St. John’s wort extract ZE117 also outperformed placebo for depressive symptoms: SMD = -1.59 and SMD = -1.02, respectively.
• Substantial heterogeneity was present (I 2 = 85.3%;95%C.I. = 81.9%;88.0%), alongside global inconsistency (Q-between-designs = 186.91, p < 0.0001).
• Confidence in the evidence was low to very low; larger efficacy estimates were associated with lower study-quality scores.

Why it matters

The review suggests that some nutraceuticals may have antidepressant potential, but the apparent benefits need cautious interpretation. Marked heterogeneity, inconsistency, and the association between larger effects and lower study quality limit confidence in the estimates. These findings underscore the importance of rigorous trials before efficacy claims can be considered dependable.

What to keep in mind

The evidence had substantial heterogeneity and global inconsistency, and overall confidence was low to very low. Several compound-specific estimates were based on few trials.