Fish Oil Flopped for Kids With Major Depressive Disorder

• A randomized trial showed no benefit from adding a daily fish oil supplement versus placebo to psychotherapy for youth with depression.
• The trial evaluated children and adolescents with moderate-to-severe major depressive disorder, including those with suicidal ideation.
• Those who started an antidepressant early had only modest improvement, emphasizing that more effective treatments for youth are needed.

Adding a daily fish oil supplement to psychotherapy showed no significant benefit over placebo for kids and teens with moderate-to-severe major depressive disorder (MDD), a randomized trial showed.

Average Children's Depression Rating Scale-Revised (CDRS-R) scores similarly improved by week 36 among youth who underwent standardized psychotherapy with an omega-3 fatty acid supplement or with placebo (adjusted mean difference 0.77 points, 95% CI -1.39 to 2.93, P=0.49), reported Gregor Berger, MD, of the University of Zurich in Switzerland, and colleagues.

Depression remission (CDRS-R score ≤28 points) actually occurred more often by week 36 with placebo than with the omega-3 supplement (31.9% vs 41.1%), as did the proportion meeting response criteria (31.2% vs 39.1% with ≥30% reduction in CDRS-R scores) by week 12.

"These findings do not support the use of 1.5 g of omega-3 fatty acids as adjunctive therapy for pediatric MDD," the authors wrote in JAMA Network Open.

"Omega-3 fatty acids have gained attention as a possible adjunctive treatment for clinical depression," they noted, which is supported by some prior data that have indicated small to moderate improvements in symptoms among adults with depression, especially when combined with antidepressants. Past studies involving adolescents and young adults have generally yielded mixed results.

"Despite widespread belief in the mood-enhancing properties of omega-3 fatty acids, supported by multiple meta-analyses and expert panels, our findings emphasize the need for rigorous evaluation of even seemingly benign interventions," Berger's team pointed out. "Promoting ineffective treatments risks delaying effective care and may worsen outcomes for adolescents with depression."

"Such delays can perpetuate the chronicity in which depressive disorders increase the risk of future suicide," they warned.

More interventions tailored for pediatric depression are needed, they urged, as suicide is currently the second leading cause of death among U.S. adolescents. In 2020, about 17% of U.S. adolescents reported at least one depressive episode.

Future studies may instead focus on testing omega-3 supplementation in specific subgroups, like youth with inflammation-linked depression.

In the current trial, Berger's team enrolled and randomized 257 youth with a DSM-4-defined single or recurrent MDD diagnosis across five Swiss child and adolescent psychiatry centers from April 2017 through March 2022.

Ages ranged from 8 to 18 years (average 15.7), and 73.2% were female. Enrollment required CDRS-R scores of 40 or greater at baseline.

Half of participants received 1.5 g of omega-3 polyunsaturated fatty acids daily, which included 1,000 mg of eicosapentaenoic acid (EPA) and 500 mg of docosahexaenoic acid (DHA). The other half received a placebo with an equivalent amount of medium-chain triglycerides. Children younger than 13 years were given a half dose. Supplements were to be taken once daily with a meal.

Pill counts and blood tests showed a high level of adherence to treatment.

All received treatment at official child and adolescent psychiatric services, which included both inpatient and outpatient facilities, provided by clinicians trained in evidence- and consensus-based guidelines for treating depressive disorders in youth.

Of the 35% of participants who were on an antidepressant at baseline, fluoxetine (46.7%) was most common, followed by sertraline (33.3%) and escitalopram (Lexapro, 12.2%).

"Notably, more than one-third of participants initiated guideline-concordant selective serotonin reuptake inhibitor therapy within 6 weeks yet showed only modest gains, underscoring the limited effectiveness of current pharmacological strategies for severe pediatric MDD and the urgent need to identify treatment-resistant trajectories earlier," the authors noted.

Similar to the trajectory of CDRS-R scores, both trial groups had clinically relevant improvements in quality of life and self-rated depression throughout the trial. Suicidal ideation also didn't differ between the groups.

Serious adverse events were comparable between the groups, with 45 in the omega-3 arm and 31 in the placebo arm. This included 28 suicide attempts. No deaths occurred.

It's possible antidepressant use may have increased placebo response rates, the authors noted, though more antidepressants were prescribed in the omega-3 group. The study also was limited by a lack of control for media use and diet.