Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression (original) (raw)
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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.
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
Omega-3 Fatty Acids for Major Depressive Disorder
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
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
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.
Preventive Medicine, 2006
Several lines of evidence indicate an association between N-3 polyunsaturated fatty acids (PUFAs) and depression. The purpose of this review was to evaluate the evidence to date within the context of the study design and methodology used. In case-control and cohort studies, concentrations of N-3 PUFAs were lower in participants with unipolar and postpartum depression. Fish are the major dietary source of N-3 PUFAs, and infrequent fish consumption is associated with depression in epidemiological studies. While these findings do not appear to be the result of confounding, in some studies failure to detect confounding may be due to a lack of power or incomplete control. In four of seven double-blind randomized controlled trials, depression was significantly improved upon treatment with at least 1 g/day of eicosapentaenoic acid, an N-3 PUFA. While clinical significance was demonstrated, preservation of blinding may be a limitation in this area of research. It remains unclear whether N-3 supplementation is effective independently of antidepressant treatment, for depressed patients in general or only those with abnormally low concentrations of these PUFAs. The relationship between N-3 PUFAs and depression is biologically plausible and is consistent across study designs, study groups, and diverse populations, which increases the likelihood of a causal relationship.
Expert Review of Neurotherapeutics, 2010
This systematic review aims to identify the effect of polyunsaturated fatty acid omega-3 on depressive disorder. A bibliographical search was conducted in the databases SciELO, PubMed and ISIWEB. The keywords used were: "depression" and "omega-3 fatty acids", "depression" and "omega-3 polyunsaturated fatty acid", "depression" and "n-3 fatty acids". A total of 19 studies were identified: four double-blind randomized studies, four cohorts, two cross-sectional lines and nine case-controls. Only five studies presented dropout of less than 30% and controlled for the most important confounding variables. Of the evaluated studies, 13 showed a significant positive association between omega-3 and depression, while six studies did not show a relationship between the referred variables. Therefore, future studies with similar methodology would aid in determining the precise effect of omega-3 on depressive disorders.
Omega-3 polyunsaturated fatty acids for major depressive disorder
Expert Opinion on Investigational Drugs, 2013
Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to