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 (original) (raw)
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Nutrients
N-3 polyunsaturated fatty acids (PUFAs) have been suggested to affect depressive disorders. This review aims to determine the effect of n-3 PUFAs on depressive symptoms in people with or without diagnosed depression. Medline, PsycINFO, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) assessing the association between n-3 PUFAs and depressive symptoms or disorders as outcomes. A random-effects meta-analysis of standardized mean difference (SMD) with 95% confidence intervals (CI) was performed. Twenty-five studies (7682 participants) were included. Our meta-analysis (20 studies) indicated that n-3 PUFA supplementation lowered depressive symptomology as compared with placebo: SMD = −0.34, 95% CI: −0.55, −0.12, I2 = 86%, n = 5836, but a possible publication bias cannot be ruled out. Subgroup analyses indicated no statistically significant difference by treatment duration of <12 vs. ≥12 weeks, presence of comorbidity, or severity of depressive sympt...
PLoS ONE, 2014
Background: Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal. Objectives: To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies. Methods: A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono-or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients. Results: Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects. Conclusions: The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.
ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review
BMJ Open, 2016
To assess the effects of n-3 polyunsaturated fatty acids (n-3PUFAs; also known as ω-3 fatty acids) compared with comparator for major depressive disorder (MDD) in adults. Design: Systematic review and meta-analyses. Data sources: The Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Registers (CCDANCTR) and International Trial Registries searched to May 2015. CINAHL searched to September 2013. Trial selection: Inclusion criteria: a randomised controlled trial (RCT); that provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and was conducted in adults with MDD. Outcomes: Primary outcomes were depressive symptomology and adverse events. Results: 20 trials encompassing 26 relevant studies were found. For n-3PUFAs versus placebo, n-3PUFA supplementation resulted in a small-to-modest benefit for depressive symptomology: SMD=−0.32 (95% CI −0.52 to −0.12; 25 studies, 1373 participants, very low-quality evidence), but this effect is unlikely to be clinically meaningful, is very imprecise and, based on funnel plot inspection, sensitivity analyses and comparison with large well-conducted trials, is likely to be biased. Considerable evidence of heterogeneity between studies was also found, and was not explained by subgroup or sensitivity analyses. Numbers of individuals experiencing adverse events were similar in intervention and placebo groups (OR=1.24, 95% CI 0.95 to 1.62; 19 studies, 1207 participants; very low-quality evidence). For n-3PUFAs versus antidepressants, no differences were found between treatments in depressive symptomology (MD=−0.70 (95% CI −5.88 to 4.48); 1 study, 40 participants, very low-quality evidence). Conclusions: At present, we do not have sufficient evidence to determine the effects of n-3PUFAs as a treatment for MDD. Further research in the form of adequately powered RCTs is needed.
Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis
Molecular Psychiatry, 2011
We conducted a meta-analysis of randomized, placebo-controlled trials of omega-3 fatty acid (FA) treatment of major depressive disorder (MDD) in order to determine efficacy and to examine sources of heterogeneity between trials. PubMed (1965-May 2010) was searched for randomized, placebo-controlled trials of omega-3 FAs for MDD. Our primary outcome measure was standardized mean difference in a clinical measure of depression severity. In stratified meta-analysis, we examined the effects of trial duration, trial methodological quality, baseline depression severity, diagnostic indication, dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in omega-3 preparations, and whether omega-3 FA was given as monotherapy or augmentation. In 13 randomized, placebo-controlled trials examining the efficacy of omega-3 FAs involving 731 participants, meta-analysis demonstrated no significant benefit of omega-3 FA treatment compared with placebo (standard mean difference (SMD) = 0.11, 95% confidence interval (CI): À0.04, 0.26). Meta-analysis demonstrated significant heterogeneity and publication bias. Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD = 0.01, 95% CI: À0.13, 0.15). Secondary analyses suggested a trend toward increased efficacy of omega-3 FAs in trials of lower methodological quality, trials of shorter duration, trials which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity. Current published trials suggest a small, non-significant benefit of omega-3 FAs for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.
Omega-3 Fatty Acids for Major Depressive Disorder: A Systematic Review
RAND Corporation eBooks, 2015
Major depressive disorder (MDD) is a prevalent condition that accounts for considerable suffering and lost productivity. Epidemiological evidence supports a potential role for dietary and/or supplemental omega-3 (n-3) fatty acids in the management of depression. We conducted a systematic review of randomized controlled trials (RCTs) that assessed the efficacy and safety of n-3 fatty acids for treating depression. We searched the electronic databases PubMed, PsycINFO, CINAHL, Embase, and AMED and screened recent existing reviews to identify English-language reports of randomized placebo-controlled or head-to-head trials testing the efficacy and safety of n-3 fatty acids as a monotherapy or adjunctive therapy to treat adults with MDD. Standard systematic review methods were used to screen the literature against a predetermined set of inclusion and exclusion criteria, abstract the study-level details and outcomes of interest, and assess the methodological quality of the studies. Effectiveness outcomes were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The quality of evidence for each conclusion was assessed using the GRADE approach. We identified 24 RCTs that met inclusion criteria; 20 studies reported efficacy outcomes for placebo comparisons. All studies combined showed a small but significant effect of n-3 fatty acids compared with placebo on depression scale scores (standardized mean difference [SMD] 0.42; 95% confidence interval [CI] 0.11, 0.73; 20 RCTs; I2 77%; low quality of evidence) and on the proportion of treatment responders (odds ratio [OR] 2.09; CI 1.25, 3.49; 13 RCTs; I2 38% moderate quality of evidence), but there was evidence of publication bias. No statistically significant effect was found for the proportion of patients in remission compared with placebo (OR 2.19; CI 0.74, 6.51; 6 RCTs; I2 52%; low quality of evidence). Benefits compared with placebo were primarily based on monotherapy studies. Only two studies compared eicosapentaenoic acid (EPA) with docosahexaenoic acid (DHA) head to head. Pooling studies of EPA alone with high EPA:DHA ratio studies revealed a significant effect on depression scale scores (SMD 0.62; CI 0.25, 0.98; 15 RCTs; I2 77%; low quality of evidence) and on the proportion of treatment responders (OR 2.31; CI 1.09, 4.88; I2 51%; low quality of evidence) compared with placebo, but studies that administered DHA or a high DHA:EPA ratio showed no effect (SMD ???0.06; CI ???0.61, 0.49; 6 RCTs; I2 68%; moderate quality of evidence). Very few studies specified depression severity. Few studies assessed effects on quality of life. N-3 fatty acids were associated with an increased risk for mild gastrointestinal symptoms compared with placebo (OR 2.58; CI 1.73, 3.91; 17 RCTs; moderate quality of evidence) but not with other categories of minor adverse events or serious adverse events. In conclusion, the n-3 fatty acid EPA may
A Meta-Analytic Review of Polyunsaturated Fatty Acid Compositions in Patients with Depression
Biological Psychiatry, 2010
Background: On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent. Methods: We conducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model. Results: Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids. Conclusions: The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted.
The Journal of Clinical Psychiatry, 2007
cause of disability worldwide by 2020, second only to ischemic heart disease, and the leading cause in developing regions. 1 The annual prevalence of major depressive disorder shows tremendous difference across different countries, nearly a 60-fold variation. 2 Based on the epidemiologic studies, societies with a high consumption of fish, which contains high amounts of omega-3 polyunsaturated fatty acids (PUFAs), appear to have a lower prevalence of major depressive disorder. 3-5 This result suggests a link between omega-3 PUFAs and the pathogenesis of depression. The PUFAs are classified into omega-3 (or n-3) and omega-6 (or n-6) groups. The parent essential fatty acid of omega-3 PUFAs is alpha-linolenic acid (ALA; C18: 3n-3), and that of the omega-6 group is linoleic acid (LA; C18:2n-6). In the central nervous system, neuronal cell membrane contains high concentrations of PUFAs, some of which cannot be synthesized and therefore must be obtained from the diet. The abnormalities in PUFA composition in cell membranes can alter membrane microstructure, cause abnormal signal transduction and immunologic dysregulation, and possibly increase the risk of developing depression. 6,7 There are studies revealing that PUFA composition may vary in different major psychiatric disorders. 8,9 Lower levels of omega-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported in serum and red blood cell membranes in patients with major depressive disorder. 10-14