Research paperA multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder
Introduction
Major depressive disorder (MDD) is a psychiatric illness resulting in heavy global burden with a clear unmet therapeutic need (Herrman et al., 2019). The antidepressant effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as their clinical safety profiles and effects on relevant biomarkers, are reported in several randomized controlled trials, subsequently aggregated into multiple meta-analyses (Chang et al., 2018a, 2018b; Firth et al., 2019; Mocking et al., 2016).
Through the advocacy of the International Society for Nutritional Psychiatry Research (ISNPR), the knowledge and evidence supporting the usage of n-3 PUFAs and various nutritional strategies for treating psychiatric illnesses are becoming mainstream (Sarris et al., 2015a, 2015b). The evidence facilitating evidence-based clinical utilization of n-3 PUFAs in MDD was further synthesized into the first clinical guidelines, published by the ISNPR in 2019 (Guu et al., 2019). Guidelines development is a process not only to present the evidence in the literature, but also to use of the wisdom-of-crowds, and integrate the evidence and empirical experiences. We applied the Delphi method to optimize independence of decisions, decentralization and aggregation of the evidence and clinical experiences. This paper describes the process employed to develop these clinical guidelines and discusses unanswered questions from clinical trials, to strengthen the guideline and enhance its clinical applicability.
Section snippets
Panel formation
Seven key members from the ISNPR had the first preparatory meeting in November 2017 and formed a steering committee. The committee used the h-index system of the Web of Science database, under the topic of “depression and omega-3″ with a timespan until the end of September 2018, to identify potential experts in this field. Subsequently, purposive snowball sampling - where existing participants recruit other participants from among their acquaintances and ISNPR members with relevant expertise-
Panel members
Fourteen experts in the fields of n-3 PUFAs and MDD were identified and invited to join the panel, eight of them were ranked among the top ten highest h-index in the Web of Science database under the category of “omega-3 and depression,” and the remaining six experts were recruited from snowball sampling. All the experts agreed to participate and completed the survey within the designated period, giving an overall response rate of 100%. Three of the panelists primarily worked in the field of
Discussion
To our knowledge, this is the first multi-disciplinary, multi-national Delphi study for the application of n-3 PUFAs in MDD treatment. Consistent with other psychiatric disorders, there remains substantial unmet need in MDD treatment. The inadequate therapeutic efficacy and problematic tolerability profiles are two major challenges that pertain to current standard antidepressant therapies, resulting in suboptimal adherence and outcomes among patients with MDD (Ho et al., 2016). Although
Conclusions
There is still inconsistency and heterogeneity in the literature regarding n-3 PUFAs as a treatment for MDD. Our Delphi study shows that consensus could nevertheless be reached. Through this process, several clinical recommendations and approaches not yet answered by clinical trials or meta-analyses were developed. We hope this article helps clinicians to better understand and contextualize previously published guidelines, allowing them to be applied to patients more easily, highlight the
Disclosures
Dr. Mischoulon has received research support from Nordic Naturals. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA, Inc. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, Blackmores, Harvard Blog, and Peer Point Medical Education Institute, LLC. He has received royalties from Lippincott Williams & Wilkins for published book “Natural Medications for Psychiatric Disorders: Considering the Alternatives.”
Jerome Sarris has received
Author contributions
TW, DM, JS and KS co-designed the study. All the authors, except WM, participated in the Delphi process. TW then drafted the manuscript, and all the authors reviewed and revised the manuscripts equally.
Role of the funding source
All the aforementioned funding bodies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, writing, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Declaration of Competing Interest
All the authors disclosed no specific conflicts of interests.
Acknowledgements
The authors of this work were supported by the following grants: MOST 108–2320-B-039–048; 108–2314-B-039–016; MOST 108–2813-C-039–133-B; 106–2314-B-039–027-MY3; and 106–2314-B-039–027 from the Ministry of Science and Technology, Taiwan; NHRI-EX108-10528NI from the National Health Research Institutes, Taiwan; CMRC-CMA-3 from Higher Education Sprout Project by the Ministry of Education (MOE), Taiwan; CMU108-SR-106 from the China Medical University, Taichung, Taiwan; and CRS-108-048, DMR-108-216
References (30)
- et al.
Systematic review and meta-analysis of omega-3-fatty acids in elderly patients with depression
Nutr. Res.
(2018) - et al.
Omega-3 polyunsaturated fatty acids and reduction of depressive symptoms in older adults: a systematic review and meta-analysis
J. Affect. Disord.
(2018) - et al.
Safety and tolerability of prescription omega-3 fatty acids: a systematic review and meta-analysis of randomized controlled trials
Prostaglandins Leukot. Essent. Fatty Acids
(2018) - et al.
Polyunsaturated fatty acids and inflammatory markers in major depressive episodes during pregnancy
Prog. Neuropsychopharmacol. Biol. Psychiat.
(2018) - et al.
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis
Lancet
(2018) - et al.
The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness
Lancet Psychiatry
(2019) - et al.
Reducing the global burden of depression: a Lancet-World Psychiatric Association Commission
Lancet
(2019) - et al.
Clinical and economic impact of non-adherence to antidepressants in major depressive disorder: a systematic review
J. Affect. Disord.
(2016) - et al.
Nutritional medicine as mainstream in psychiatry
Lancet Psychiat.
(2015) - et al.
The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: acting separately or synergistically?
Prog. Lipid Res
(2016)
Omega-3 fatty acids in the prevention of interferon-alpha-induced depression: results from a randomized, controlled trial
Biol. Psychiat.
Omega-3 fatty acids for depression in adults
Cochrane Database Syst. Rev.
omega-3 fatty acids for major depressive disorder in adults: an abridged Cochrane review
BMJ Open
Antidepressant drug effects and depression severity: a patient-level meta-analysis
JAMA
Omega-3 fatty acids and gestational length in a high-risk psychiatric population due to psychiatric morbidity and medication exposure during pregnancy
J. Clin. Psychopharmacol.
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