Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial

Nutr Neurosci. 2018 Apr;21(3):224-228. doi: 10.1080/1028415X.2017.1283128. Epub 2017 Feb 22.


Overview: Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD).

Methods: A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured.

Results: After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found.

Conclusion: Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression.

Keywords: Adjunctive; DHA; Depression; Docosahexaenoic acid; Omega-3.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Combined Modality Therapy / adverse effects
  • Depression / diet therapy
  • Depression / drug therapy
  • Depression / physiopathology
  • Depression / therapy
  • Depressive Disorder, Major / diet therapy*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / therapy
  • Depressive Disorder, Treatment-Resistant / diet therapy*
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Depressive Disorder, Treatment-Resistant / physiopathology
  • Depressive Disorder, Treatment-Resistant / therapy
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dietary Supplements* / adverse effects
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / adverse effects
  • Docosahexaenoic Acids / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mood Disorders / chemically induced
  • Mood Disorders / etiology
  • Mood Disorders / prevention & control
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Psychotherapy*
  • Severity of Illness Index
  • Sleep Disorders, Intrinsic / etiology
  • Sleep Disorders, Intrinsic / prevention & control


  • Antidepressive Agents
  • Antipsychotic Agents
  • Docosahexaenoic Acids