A clinical practice guideline from the International Society for Nutritional Psychiatry Research (ISNPR) recommends omega-3 polyunsaturated fatty acids (PUFAs) as adjunctive therapy for major depressive disorder (MDD).

The value of omega-3 PUFAs in depression is "overlooked," even though accumulating evidence supports it. This therapy "needs to be on the radar" of physicians, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, told Medscape Medical News.

Su, a founding member of the ISNPR and a strong proponent of "nutritional psychiatry," organized a subcommittee of the ISNPR and invited the top 10 most-cited authors in the use of omega-3 PUFAs for depression to review the literature and develop the practice guideline on appropriate prescribing of omega-3 fatty acids for MDD.

The consensus guideline was published online September 3 in Psychotherapy and Psychosomatics.

Prophylaxis, Maintenance

The guideline emphasizes the importance of accurate clinical diagnosis and measurement-based psychopathologic assessments in the therapeutic setting when recommending omega-3 PUFAs for depression.

The guideline notes that there is a growing body of evidence demonstrating the efficacy of n-3 PUFAs as an adjunctive treatment for MDD. The guideline authors also note that omega-3s are safe and effective for accelerating the effect of antidepressants at treatment initiation and for augmenting existing antidepressant therapy when efficacy is inadequate.

With respect to formulation and dosage, the guideline recommends pure eicosapentaenoic acid (EPA) or a combination of EPA and docosahexaenoic acid, with net EPA starting from at least 1 g/day up to 2 g/day for at least 8 weeks as adjunctive treatment. Importantly, the authors note that the quality of n-3 PUFAs may affect therapeutic activity.

The guideline also endorses n-3 PUFAs as a potential prophylactic treatment for high-risk populations, in addition to standard medical care. The duration of acute n-3 PUFA treatment may be extended to include maintenance treatment to prevent recurrence.

Potential side effects, such as gastrointestinal and dermatologic conditions, should be monitored, and comprehensive metabolic panels should be obtained during treatment, the guideline authors note.

They call for further research into personalizing the clinical application of n-3 PUFAs in subgroups of patients with MDD whose omega-3 index is low or who have high levels of inflammatory markers.

The panel acknowledges in the guideline that there is ongoing debate on the benefits of omega-3 PUFAs for MDD. Meta-analyses have shown "only small but statistically significant effects," the authors write.

They note that in three meta-analyses, the estimated effect sizes (standardized mean differences between n-3 PUFAs and placebo) ranged from 0.23 to 0.56, with wide confidence intervals (CIs).

However, small effect sizes have also been reported regarding antidepressant drugs compared to placebo (standardized mean differences, 0.30 – 0.47, with narrower CIs).

Given that currently recommended therapies for MDD have only small effects, the panel notes three "practical" strategies that should be employed to address the "unmet" need in depression treatment.

These include an open-minded attitude to integrative intervention; the application of personalized medicine; and a shared decision-making process based on balanced information to enhance treatment adherence.

Reasonable Approach

Commenting for Medscape Medical News, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Northwell Health's Staten Island University Hospital in New York City, said the recommendation constitutes a "perfectly reasonable practice guideline.

"The big picture, however, is that while there is a literature on the usefulness of omega-3s, average clinical experience hasn't been as impressive. Clinicians generally haven't been overwhelmed by the results. There are practitioners that favor them more than others," said Sullivan.

"Conceptually," he added, "what's appealing about omega-3s is we know that depressive states are associated with dysregulation of the immune system, and agents like the omega-3s appear to have a role in helping to re-regulate or positively regulate the immune system and combat some of the metabolic effects of stress. But it's still an area that we need to understand more about."

The guideline authors were supported by research grants from the Ministry of Science and Technology, Taiwan; the National Health Research Institutes, Taiwan; and the Chinese Medicine Research Center from the China Medical University. Su is a founding committee member of the ISNPR, the board director of the International Society for the Study of Fatty Acids, and an associate editor of Brain, Behavior and Immunity. The original article contains a complete list of authors' relevant financial relationships. Sullivan has disclosed no relevant financial relationships.

Psychother Psychosom. Published online September 3, 2019. Full text

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