오메가3 보충제의 우울증에 대한 효과

오메가 3 지방산 (Omega-3 (ω-3) fatty acids)은 일부 임상 시험에 근거하여 때때로 우울증 치료의 보조제로 사용됩니다. 관련된 의문은 오메가 3 보충제를 복용하는 것이 일반 인구에서 우울증을 예방할 수 있느냐는 것입니다. 이 질문을 해결하기 위해 연구자들은 이전에 발표된 VITAL 연구 데이터를 사용하여 매일 위약 또는 1 그람 fish oil (465 mg eicosapentaenoic acid [EPA] and 375 mg docosahexaenoic acid)을 할당하였던 18,000명의 참가자 (평균 나이, 68세)를 평가했습니다. 대부분 참가자들은 우울증 병력이 없었고, 이외 참가들도 적어도 2년 동안 우울증이 없었습니다.

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중간값 5년 이상 추적 관찰 동안, 임상적으로 진단된 우울증 발생률은 오메가 3 그룹에서 약간이지만 의미 있게 더 컸으며 주로 여성의 과도한 위험으로 인하여 발생했습니다. 매년 평가되는 validated depresssion inventory 점수는 두 그룹에서 유사했습니다.

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■ 이 결과는 일반 인구에서 우울증 예방을 위해 fish oil 사용을 지지하지 않습니다. 최근 연구들은 더 높은 용량의 단독 EPA가 심혈관 위험을 낮출 수 있다는 것을 제안했지만, 이 연구의 어떠한 것도 이러한 접근이 우울증 예방에 유용한 접근임을 제안하지 않습니다.

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Key Points

Question Does long-term supplementation with marine omega-3 fatty acids (omega-3) prevent depression in the general adult population?

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Findings In this randomized clinical trial that included 18 353 adults aged 50 years or older without depression or clinically relevant depressive symptoms at baseline, daily omega-3 supplementation compared with placebo resulted in mixed findings of a statistically significant increase in risk of depression or clinically relevant depressive symptoms (hazard ratio, 1.13) but no significant difference in change in 8-item Patient Health Questionnaire depression scale mood scores (0.03 points, comparing omega-3 with placebo), over a 5-year treatment period.

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Meaning These findings do not support the use of omega-3 fatty acid supplements in adults to prevent depression.

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Abstract

Importance Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown.

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Objective To test effects of omega-3 supplementation on late-life depression risk and mood scores.

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Design, Setting, and Participants A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017.

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Interventions Randomized 2 × 2 factorial assignment to vitamin D3 (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo.

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Main Outcomes and Measures Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale).

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Results Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, −0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%).

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Conclusions and Relevance Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression.

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Trial Registration ClinicalTrials.gov Identifiers: NCT01696435 and NCT01169259

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REF. JAMA. 2021;326(23):2385-2394. doi:10.1001/jama.2021.21187

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