High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis

BACKGROUND: The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment. METHODS: Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs. RESULTS: A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose. CONCLUSIONS: High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.