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Cochrane Database of Systematic Reviews

Omega‐3 fatty acids for depression in adults

Overview of attention for article published in Cochrane database of systematic reviews, November 2021
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

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5 news outlets
3 blogs
44 X users
2 Facebook pages
7 Wikipedia pages
1 YouTube creator


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Omega‐3 fatty acids for depression in adults
Published in
Cochrane database of systematic reviews, November 2021
DOI 10.1002/14651858.cd004692.pub5
Pubmed ID

Katherine M Appleton, Philip D Voyias, Hannah M Sallis, Sarah Dawson, Andrew R Ness, Rachel Churchill, Rachel Perry


Major depressive disorder (MDD) is highly debilitating, difficult to treat, has a high rate of recurrence, and negatively impacts the individual and society as a whole. One potential treatment for MDD is n-3 polyunsaturated fatty acids (n-3PUFAs), also known as omega-3 oils, naturally found in fatty fish, some other seafood, and some nuts and seeds. Various lines of evidence suggest a role for n-3PUFAs in MDD, but the evidence is far from conclusive. Reviews and meta-analyses clearly demonstrate heterogeneity between studies. Investigations of heterogeneity suggest different effects of n-3PUFAs, depending on the severity of depressive symptoms, where no effects of n-3PUFAs are found in studies of individuals with mild depressive symptomology, but possible benefit may be suggested in studies of individuals with more severe depressive symptomology. Hence it is important to establish their effectiveness in treating MDD. This review updates and incorporates an earlier review with the same research objective (Appleton 2015). To assess the effects of n-3 polyunsaturated fatty acids (also known as omega-3 fatty acids) versus a comparator (e.g. placebo, antidepressant treatment, standard care, no treatment, wait-list control) for major depressive disorder (MDD) in adults. We searched the Cochrane Central Register of Controlled trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO together with trial registries and grey literature sources (to 9 January 2021). We checked reference lists and contacted authors of included studies for additional information when necessary. We included studies in the review if they: used a randomised controlled trial design; provided n-3PUFAs as an intervention; used a comparator; measured depressive symptomology as an outcome; and were conducted in adults with MDD. Primary outcomes were depressive symptomology (continuous data collected using a validated rating scale) and adverse events. Secondary outcomes were depressive symptomology (dichotomous data on remission and response), quality of life, and non-completion of studies. We used standard methodological procedures as expected by Cochrane. We assessed the certainty of the evidence using GRADE criteria. The review includes 35 relevant studies: 34 studies involving a total of 1924 participants investigated the impact of n-3PUFA supplementation compared to placebo, and one study involving 40 participants investigated the impact of n-3PUFA supplementation compared to antidepressant treatment. For the placebo comparison, n-3PUFA supplementation resulted in a small to modest benefit for depressive symptomology, compared to placebo: standardised mean difference (SMD) (random-effects model) -0.40 (95% confidence interval (CI) -0.64 to -0.16; 33 studies, 1848 participants; very low-certainty evidence), but this effect is unlikely to be clinically meaningful. An SMD of 0.40 represents a difference between groups in scores on the HDRS (17-item) of approximately 2.5 points (95% CI 1.0 to 4.0), where the minimal clinically important change score on this scale is 3.0 points. The confidence intervals include both a possible clinically important effect and a possible negligible effect, and there is considerable heterogeneity between studies. Sensitivity analyses, funnel plot inspection and comparison of our results with those of large well-conducted trials also suggest that this effect estimate may be biased towards a positive finding for n-3PUFAs. Although the numbers of individuals experiencing adverse events were similar in intervention and placebo groups (odds ratio (OR) 1.27, 95% CI 0.99 to 1.64; 24 studies, 1503 participants; very low-certainty evidence), the confidence intervals include a small decrease to a modest increase in adverse events with n-3PUFAs. There was no evidence for a difference between n-3PUFA and placebo groups in remission rates (OR 1.13, 95% CI 0.74 to 1.72; 8 studies, 609 participants, low-certainty evidence), response rates (OR 1.20, 95% CI 0.80 to 1.79; 17 studies, 794 participants; low-certainty evidence), quality of life (SMD -0.38 (95% CI -0.82 to 0.06), 12 studies, 476 participants, very low-certainty evidence), or trial non-completion (OR 0.92, 95% CI 0.70 to 1.22; 29 studies, 1777 participants, very low-certainty evidence). The evidence on which these results are based was also very limited, highly heterogeneous, and potentially biased. Only one study, involving 40 participants, was available for the antidepressant comparison. This study found no differences between treatment with n-3PUFAs and treatment with antidepressants in depressive symptomology (mean difference (MD) -0.70, 95% CI -5.88 to 4.48), rates of response to treatment (OR 1.23, 95% CI 0.35 to 4.31), or trial non-completion (OR 1.00, 95% CI 0.21 to 4.71). Confidence intervals are however very wide in all analyses, and do not rule out important beneficial or detrimental effects of n-3PUFAs compared to antidepressants. Adverse events were not reported in a manner suitable for analysis, and rates of depression remission and quality of life were not reported. At present, we do not have sufficient high-certainty evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses may suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the certainty of the evidence on which this result is based to be low to very low. Our data may also suggest similar rates of adverse events and trial non-completion in n-3PUFA and placebo groups, but again our estimates are very imprecise. Effects of n-3PUFAs compared to antidepressants are very imprecise and uncertain. More complete evidence is required for both the potential positive and negative effects of n-3PUFAs for MDD.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 240 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Unknown 239 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 32 13%
Student > Master 20 8%
Researcher 17 7%
Other 16 7%
Student > Ph. D. Student 10 4%
Other 23 10%
Unknown 122 51%
Readers by discipline Count As %
Medicine and Dentistry 40 17%
Nursing and Health Professions 27 11%
Agricultural and Biological Sciences 9 4%
Neuroscience 6 3%
Psychology 6 3%
Other 22 9%
Unknown 130 54%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 87. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 June 2024.
All research outputs
of 26,205,030 outputs
Outputs from Cochrane database of systematic reviews
of 13,193 outputs
Outputs of similar age
of 528,126 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 173 outputs
Altmetric has tracked 26,205,030 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,193 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 34.8. This one has done particularly well, scoring higher than 93% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 528,126 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 173 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.