Elsevier

Journal of Affective Disorders

Volume 265, 15 March 2020, Pages 233-238
Journal of Affective Disorders

Research paper
A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder

https://doi.org/10.1016/j.jad.2020.01.050Get rights and content

Highlights

  • The international society for nutritional psychiatry research (ISNPR) developed the first practice guideline for n-3 polyunsaturated fatty acids (PUFA) in major depressive disorder treatment in 2019, but gaps were noted between evidence and consensus.

  • Five major themes, including 1) general concepts, 2) acute treatment strategy, 3) depression recurrence monitoring and prevention, 4) special populations, and 5) safety issues, were presented in the guidelines.

  • “N-3 PUFAs are one of the potential adjunctive treatments for adult MDD” reached the highest agreement and is based on high level of evidence, while “n-3 PUFAs are one of the potential monotherapies for adult MDD” was not endorsed by consensus and had limited supporting evidence.

  • Interestingly, there were items, especially in themes including “special populations,” reached high consensus agreement despite sub-optimal evidence, implying not only the Delphi process could explore the gaps between evidence and practice, but also pointing out future research directions.

Abstract

Introduction

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are recommended as an integrative treatment for major depressive disorder (MDD). In 2019, the International Society for Nutritional Psychiatry Research (ISNPR) developed the first practice guidelines for n-3 PUFA treatment of MDD. To strengthen these guidelines and enhance their clinical applicability, we synthesized the evidence and clinical experiences previously obtained through the Delphi methodology.

Methods

Nineteen statements covering five major domains in MDD treatment were formulated through internal meetings. Fourteen international experts were invited to participate in the web-based Delphi process that validated the statements. Likert scales were used, and consensus level was set at 7.0/10.0, with the equivocal level set at 5.1–6.9. The items with scores < 5.0 were allocated into a second round Delphi survey with inverse questions.

Results

All panelists completed the survey. Sixteen statements reached consensus, and the statement “n-3 PUFAs are one of the potential adjunctive treatments for adult MDD” reached the highest agreement. “N-3 PUFAs are one of the potential monotherapies for adult MDD” instead scored lowest. Regarding “special populations,” many items, reached high consensus despite sub-optimal supportive evidence.

Limitation

The panelists had a specialized interest in n-3 PUFAs; focus was placed on clinical issues rather than on biological mechanisms.

Conclusions

The Delphi process helps bridge the gap between scientific evidence and clinical practice, supports certain uses of PUFA and identifies insufficiency in current evidence that merit future research.

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

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