Omega-3 fatty acid supplementation for depression in children and adolescents

Abstract:

Background: 

Mental health disorders including major depressive disorder (MDD) are well recognized as major contributors to the global burden of disease among adolescents. The prevalence of adolescent depression is estimated to have increased by at least 25% during the COVID-19 pandemic, compounding the already challenging problem of insufficient mental health service and service accessibility that existed prepandemic.

Omega-3 polyunsaturated fatty acid (PUFA) supplementation is currently recommended as a preventive treatment for depression in high-risk adults as well as a second-line monotherapy for adults with mild to moderate MDD, and adjunctive to antidepressants for adults with moderate to severe MDD.

The benefits of omega-3 PUFA intake on depressive illness have been hypothesized to occur as a result of their effect on neurotransmission, maintenance of membrane fluidity, and anti-inflammatory action.

A comprehensive synthesis and quantification of the existing evidence on omega-3 PUFA's efficacy in treating depression among children and adolescents is essential for clinicians to provide informed guidance to young people and their families, especially considering the absence of current guidelines for this age group.

Objectives: 

Primary objective: To determine the impact of omega-3 PUFA supplementation versus a comparator (e.g. placebo, wait list controls, no treatment/supplementation, or standard care) on clinician-diagnosed depression or self-reported depression symptoms in children and adolescents.

Secondary objectives: To estimate the size of the effect of omega-3 PUFAs on depression symptoms. To estimate the effect of each type of omega-3 PUFA (EPA or DHA), compared with placebo, on depression. To determine if the effect is modified by dosage, format (capsule or liquid), sex, or age. To determine compliance and attrition for omega-3 PUFAs as an intervention for depression in children and adolescents. To determine the safety of omega-3 PUFAs as an intervention for depression in children and adolescents.

Search methods: We searched CENTRAL, MEDLINE, Embase, three other databases, reference lists of included studies, grey literature, and relevant reviews. The latest search date was 18 May 2023.

Selection criteria: We included randomized controlled trials (RCTs) involving males and females aged 19 years or younger with diagnosed depression comparing omega-3 PUFA supplementation to placebo, wait list control, no treatment/supplementation, or standard care.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were self-reported depression symptoms and clinically diagnosed resolution of depression. Our secondary outcomes were attrition, adverse effects, and compliance with the intervention. We used GRADE to assess the certainty of evidence for key outcomes.

Main results: 

We included five trials with 228 participants in our meta-analysis. All trials used a placebo comparator; intervention duration ranged from 10 to 16 weeks (median: 12 weeks).

Omega-3 PUFA supplementation compared to placebo may reduce self-reported depression symptoms, but the evidence is very uncertain (standardized mean difference [SMD] -0.34, 95% confidence interval [CI] -0.85 to 0.17; lower SMD means greater improvement in depression due to omega-3 PUFA; 5 trials, 185 participants; very low-certainty evidence).

Omega-3 PUFA supplementation may have little to no effect on remission of depression symptoms compared to placebo, but the evidence is very uncertain (omega-3 PUFA versus placebo: 50% versus 48%; odds ratio [OR] 1.11, 95% CI 0.45 to 2.75; 4 trials, 127 participants; very low-certainty evidence).

Omega-3 PUFA supplementation may result in little to no difference in attrition (dropouts) compared to placebo (omega-3 PUFA versus placebo: 18% versus 19%; OR 0.94, 95% CI 0.46 to 1.90; 5 trials, 228 participants; low-certainty evidence).

Omega-3 PUFA supplementation may result in little to no difference in adverse effects, with one study reporting more muscle cramps in the fish oil group (13/27 participants) compared to the placebo group (6/29 participants); one study reported more frequent defecation in the omega-3 group (1/29 participants) and one study identified mild skin rash and unusual/manic behavior in the placebo group (2/27 participants). None of the included studies reported serious adverse effects.

Authors' conclusions: 

Based on five small studies, omega-3 PUFA supplementation may reduce self-reported depression symptoms, but the evidence is very uncertain.

Omega-3 PUFA supplementation may have little to no effect on depression remission compared to placebo, but the evidence is very uncertain. Omega-3 PUFA supplementation may result in little to no difference in attrition or adverse effects. The studies observed no serious adverse effects.

This review highlights early-stage research on omega-3 PUFA and depression in young people. The evidence on the effects of omega-3 PUFA supplementation in improving self-reported depression symptoms or achieving depression remission in children and adolescents is very uncertain.

While no harms are evident, more data are needed to confirm potential risks. Addressing current limitations in the evidence base through the design and conduct of methodologically rigorous studies - larger sample sizes, varied dosages, eicosapentaenoic acid/docosahexaenoic acid ratios, treatment durations, and safety profiles - is crucial to advance our understanding of the role of omega-3 PUFA supplementation for depression in children and adolescents.

Plain language summary

Is omega‐3 polyunsaturated fatty acid supplementation better than a placebo for treating depression among children and adolescents?

Key messages

– Due to a lack of robust evidence, the benefits and unwanted effects of omega‐3 polyunsaturated fatty acids (which are important fats that you must obtain from your diet) supplementation for treating depression among children and adolescents are unclear.

– Larger, well‐designed studies are needed to give better estimates of the potential benefits and harms of omega‐3 polyunsaturated fatty acid supplementation for child and adolescent depression.

Why is it important to find treatments for children and adolescents with depression?

People with depression have a low mood or lose pleasure or interest in usual activities. It is a long‐lasting (chronic) disorder that is both serious and recurrent (it can return after periods of feeling well). It often begins during childhood and adolescence, affecting up to eight in every 100 children.

Unfortunately, response to current treatments for depression in children and adolescents is poor, and relieving symptoms (remission) can be challenging.

In recent studies, supplements of omega‐3 polyunsaturated fatty acids have shown promise as a potential treatment for depression in adults. Our body cannot make these beneficial fats, but they are naturally present in oily fish, marine sources, and certain nuts and seeds. They can also be given as daily supplements in capsule or liquid forms (for example, as cod liver oil capsules).

What did we want to find out?

We wanted to find out:

– if omega‐3 polyunsaturated fatty acids supplementation works to decrease symptoms of depression in children and adolescents; and

– if omega‐3 polyunsaturated fatty acids supplementation helps children and adolescents achieve remission from depression.

We also wanted to know if omega‐3 polyunsaturated fatty acids supplementation can cause any unwanted effects.

What did we do?

We searched for studies in which children and adolescents were assigned randomly to two or more treatment groups that compared omega‐3 polyunsaturated fatty acids supplementation with a placebo (pretend treatment with the same appearance), on a waiting list, no treatment/supplementation, or usual care. This is the best way to ensure that groups of people are similar and that investigators do not know who is in which group. We compared and summarized their results, and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found five studies that involved 228 children and adolescents ranging from 10 to 16 years of age with depression. The largest study included 60 people, and the smallest study included 28 people. Three studies were conducted in the USA, one in Israel, and one in Slovakia. Four studies lasted for around 12 weeks and one study lasted for 16 weeks.

We found that omega‐3 polyunsaturated fatty acids supplementation may reduce self‐reported depression symptoms, but the results are very uncertain. If omega‐3 PUFA supplements and placebos were given to a group of 100 children and adolescents with depression, then 50 children receiving omega‐3 polyunsaturated fatty acids would achieve remission and 48 receiving the placebo would achieve remission.

What are the limitations of the evidence?

We are not confident in the evidence because there were not enough studies to be certain about the results, and the studies were very small. To date, there is insufficient evidence to determine if omega‐3 polyunsaturated fatty acids supplementation improves depression for children and adolescents.

How up to date is this evidence?

The evidence is up to date to 18 May 2023.