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Journal of Affective Disorders
journal homepage: www.elsevier.com/locate/jad
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
Ta-Wei Guua,b, David Mischoulonc, Jerome Sarrisd,e, Joseph Hibbelnf, Robert K. McNamarag,
Kei Hamazakih, Marlene P. Freemani, Michael Maesj, Yutaka J. Matsuokak, R.H. Belmakerl,
Wolfgang Marxm, Carmine Parianten, Michael Berkm,o, Felice Jackam, Kuan-Pin Sua,p,q,⁎
a Departments of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, TAIWAN
bDivision of Psychiatry, Departments of Internal Medicine, China Medical University Beigang Hospital, Yunlin, TAIWAN
c Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
dNICM, Health Research Institute, Western Sydney University, Westmead, NSW, AUSTRALIA
e The Melbourne Clinic, Professorial Unit, Department of Psychiatry, Melbourne University, VIC, AUSTRALIA
f Section on Nutritional Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA
g Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA
hDepartment of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan
i Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, MA, USA
jDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
k Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Tokyo, Japan
l Ben Gurion University of the Negev, Beersheba, Israel
mDeakin University, Faculty of Health, School of Medicine, IMPACT SRC and the Food & Mood Centre, Australia
n Stress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
oOrygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the
Department of Psychiatry, The University of Melbourne, Melbourne, Australia
p Tainan Municipal An-Nan Hospital, China Medical University, Tainan, TAIWAN
q College of Medicine, China Medical University, Taichung, TAIWAN
A R T I C L E I N F O
Keywords:
Delphi
DHA
EPA
guideline
major depressive disorder
A B S T R A C T
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 va-
lidated 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.
https://doi.org/10.1016/j.jad.2020.01.050
Received 10 September 2019; Received in revised form 5 January 2020; Accepted 13 January 2020
⁎ Corresponding author:
E-mail address: cobolsu@gmail.com (K.-P. Su).
Journal of Affective Disorders 265 (2020) 233–238
Available online 15 January 2020
0165-0327/ © 2020 Elsevier B.V. All rights reserved.
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https://www.elsevier.com/locate/jad
https://doi.org/10.1016/j.jad.2020.01.050
https://doi.org/10.1016/j.jad.2020.01.050
mailto:cobolsu@gmail.com
https://doi.org/10.1016/j.jad.2020.01.050
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1. 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 poly-
unsaturated 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). Guide-
lines 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 pro-
cess employed to develop these clinical guidelines and discusses un-
answered questions from clinical trials, to strengthen the guideline and
enhance its clinical applicability.
2. Methods
2.1. 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 partici-
pants recruit other participants from among their acquaintances and
ISNPR members with relevant expertise- was employed in order to
enhance representativeness. Since this Delphi survey was focused on
the clinical application of n-3 PUFAs, experts with a predominant focus
on basic research were excluded. An invitation email with the online
survey link was sent to the identified experts (including the steering
committee members).
2.2. Literature review and questionnaire development
Four core authors (TG, DM, JS, and KS) conducted a systematic
review with an emphasis on randomized-controlled trials (RCTs), sys-
tematic reviews, and meta-analyses via PubMed and the Cochrane
Database; this review focused on the quality of evidence and the im-
plications, and included studies from inception to May 29, 2019 using
the terms “omega-3 polyunsaturated fatty acids,” “n-3 PUFAs,” “major
depressive disorder,” and “treatment.” All four authors then examined
cross-referencing, identified missing studies, and discussed and revised
the draft of the review through subsequent on-line conferences. The
evidence levelwas categorized using a modified format of the 2011
Levels of Evidence grading system from I-IV developed by the Oxford
Center for Evidence-Based Medicine, as described in Table 1.
After compiling evidence from the literature and completing the
systematic review, TG drafted the initial key questions covering five
major themes: 1) general concepts; 2) acute treatment strategies; 3)
depression recurrence monitoring and prevention; 4) special popula-
tions; and 5) safety issues. These questions were then shared with other
core authors, with a request for additional questions, leading to a full
questionnaire with a total of 19 closed questions and one open-ended
question.
2.3. Delphi method
The Delphi method has demonstrated usefulness for complex real-
world problems, especially when evidence needs further improvement
or translation. Modern Delphi processes are often applied online
(Jorm, 2015). We disseminated the questionnaire using a web-based
survey platform (SurveyMonkey) for online voting, and the survey was
open for two weeks (2018/10/13-2018/10/27, with an additional day
added due to potential time zone differences). The experts in-
dependently rated the extent to which they agreed with the nineteen
closed questions relevant to n-3 PUFAs clinical use, and provided fur-
ther comments in response to open-ended questions.
2.4. Data analyses
A Likert scale (from zero to ten) was used for the 19 closed ques-
tions/statements (zero = fully against, ten = fully agree). The con-
sensus level was predefined as a score above 7.0/10.0 (consensus
agreement, with unanimous agreement defined as 10.0/10.0), and equi-
vocal result was defined as between 5.1 to 6.9 (majority agreement) for
the closed questions, while items scoring lower than 5.0 were allocated
into a proposed second round Delphi survey with inverse questions
(questions worded in the opposite way compared to the original, e.g.,
“N3-PUFAs could be prescribed for children and adolescents with MDD”
will be asked as “N3-PUFAs could not be prescribed for children and
adolescents with MDD”). The questionnaire responses were first auto-
matically aggregated by the online platform, and then both the closed
questions and the open-ended questions were analyzed by TW and KS,
and the complete results were presented to all the panelists. The com-
plete process of the study is summarized in Fig. 1.
3. Results
3.1. 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 re-
cruited 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 nutritional sciences, while the rest of the panelists were
the field of psychiatry. Geographically, the panelists came from Asia,
Australasia, Europe and North America, and the details of panelists’
characteristics are shown in Table 2.
Table 1
Levels of evidence.
Level I Systematic reviews or meta-analyses of randomized controlled trials with narrow confidence interval or consistent results.
Level II Systematic reviews or meta-analyses of randomized controlled trials with wide confidence interval or inconsistent results; or at least one well-designed randomized
controlled trial.
Level III Non-randomized controlled cohort/follow-up studies.
Level IV Appropriate and important reviews, case series and case reports and judged by experts during the meeting and discussions.
T.-W. Guu, et al. Journal of Affective Disorders 265 (2020) 233–238
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3.2. Agreement of n-3 PUFAs clinical usage for MDD
The complete Delphi survey results are presented in Table 3. Sixteen
out of the nineteen statements reached the consensus agreement
threshold (average Likert scale rating >7/10) and were endorsed by
the expert panel. None of the statements scored below 5.0, so the
proposed second round Delphi survey was not required, and was re-
placed by online discussions. The following three statements that
reached majority agreement only (equivocal) were “N-3 PUFAs are one
of the potential monotherapies for adult MDD (5.93/10.0, General Con-
cepts); ” “Pure EPA is more recommended than EPA/DHA (>2) combi-
nation (6.57/10.0, General Concepts); ” and “N3-PUFAs are considered
similarly effective for recurrent MDD, compared with treatment-naïve MDD,
as an adjunctive treatment (6.86/10.0, Recurrence and Prevention).”
The sixteen statements that reached the consensus threshold were
synthesized into the ISNPR guidelines along with the literature review
(Guu et al., 2019); among them, there was a large score discrepancy
(from 7.14 to 9.43 out of 10.0). Notably, there was some consensus
statements with only lower levels (level II or lower) of supportive evi-
dence, mostly in the themes of “Acute Treatment Strategy” and
“Safety.” Also, some items that reached consensus threshold of agree-
ment were supported by not only lower levels of evidence, but also
evidence that was either limited or inconclusive, especially in the
themes of “Recurrence and Prevention” and “Special Populations.”
4. 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 accumulating evidence suggests that adjunctive EPA and DHA
may add to the efficacy of antidepressants with a sound tolerability
profile, the pooled estimated effect sizes only range from 0.23–0.56 in
treating DSM-defined MDD patients (Appleton et al., 2015;
Grosso et al., 2014; Lin et al., 2012). Importantly, there has been cri-
ticism of trials included in meta-analyses, due to issues of high het-
erogeneity and wide confidence intervals (Appleton et al., 2016). Al-
though there are similarly modest effect sizes (range between 0.30 and
0.47) reported in antidepressant trials (Cipriani et al., 2018;
Fournier et al., 2010; Kirsch et al., 2008), the issues of heterogeneity
and wide confidence intervals often mean that clinicians are hesitant to
consider n-3 PUFAs as a treatment for MDD patients. In this Delphi
study, we aimed to manage the gaps between evidence and practice,
address the heterogeneity in the literature, and improve the applic-
ability of the ISNPR guidelines.
4.1. Differences between consensus degree and practice
In the Delphi study, despite categorized items reaching consensus, it
is notable that their scores varied widely. For example, “N-3 PUFAs are
one of the potential adjunctive treatments for adult MDD” unsurprisingly
reached the highest agreement among experts (9.43/10.0), as there
were already several independent randomized-controlled trials and
subsequently meta-analyses consistently suggesting the benefit of n-3
PUFAs used in addition to antidepressants (Hallahan et al., 2016;
Mocking et al., 2016). On the other hand, “The dose is recommended to be
increased in 2 weeks for non- or partial responders, and titrated up to the
Fig. 1. Flow Diagram of the N-3 Guideline for Depression Development Process.
Table 2
Delphi panel respondents’ characteristics (N = 14).
Delphi panel respondents
Gender, n (%)
Female 2 (14%)
Male 12 (86%)
Primary area of practice, n (%)
Psychiatry 11 (79%)
Nutritional Sciences 3 (21%)
Geographic area of practice, n (%)
Asia 5 (36%)
Australasia 3 (21%)
Europe* 2 (14%)
North America 4 (28%)
⁎ Israel is considered a European country in this study.T.-W. Guu, et al. Journal of Affective Disorders 265 (2020) 233–238
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maximum dose in 4–6 weeks if tolerable” only marginally achieved con-
sensus level (7.14/10.0). However, some experts disclosed that their
reasons for disagreeing with this item, stating “because with n-3 PUFAs,
we can go directly to therapeutic levels to get the patient optimized as
soon as possible.” This implies that although there was not a clear dose-
titration strategy in the literature previously, n-3 PUFAs are considered
a safe and well-tolerated nutrient that can be up-titrated rapidly for
potentially better and faster responses.
4.2. Heterogeneity in the evidence
In addition to the score differences between the consensus items, it
is also interesting to compare all the items two-dimensionally, re-
viewing the supporting evidence behind them and the level of con-
sensus reached.
First, among the three non-consensus items, “N-3 PUFAs are one of
the potential monotherapies for adult MDD (5.93/10.0)” scored the
lowest, followed by “Pure EPA is more recommended than EPA/DHA
(>2) combination (6.57/10.0)” and “N3-PUFAs are considered similarly
effective for recurrent MDD, compared with treatment-naïve MDD, as an
adjunctive treatment (6.86/10.0).” Indeed, the evidence behind these
items is inconclusive. For example, only a few studies have used n-3
PUFAs as a monotherapy in MDD patients of heterogenous physical
conditions and with inconsistent results (Mischoulon et al., 2015;
Nemets et al., 2006; Su et al., 2008; Zimmer et al., 2013). There are also
very limited clinical trial data comparing the effectiveness of n-3 PUFAs
between treatment-naïve MDD and recurrent-MDD patients. Also, pure
EPA is not yet available in many countries, which has not only limited
the conduct of clinical trials with EPA, but also influenced the clinical
experience of the experts and therefore the consensus results.
Second, there were also items that were supported by lower levels of
evidence, yet reached consensus thresholds of agreement, including:
“For non-responders, it is recommended to evaluate the quality of n-3 PUFA
supplementary products (7.64/10.0; Level II evidence)”; and “If clinicians
are not familiar with high quality n-3 PUFAs in the market, they should
consider prescription omega-3 fatty acid products (RxOM3FAs) (8.29/10.0;
Level IV evidence).” Since the Delphi process was aimed at facilitating
clinical applicability, some of the questions, including these, were de-
signed to translate the results and experiences of n-3 PUFA clinical
trials, and were rather straightforward and intuitive. As these items
reached consensus threshold of agreement, it is recommended that
appropriate government agencies should consider regulating the
quality of n-3 PUFA products and clinicians should check the quality of
the n-3 PUFAs in their markets.
Finally, but most interestingly, there were items with lower levels
of, and limited or inconclusive supporting evidence, which still reached
a high degree of consensus, especially in the themes of “Recurrence and
Prevention (questions 11: “N-3 PUFAs could be recommended as a poten-
tial prophylactic treatment for high-risk populations (alongside standard
medical care) (7.50/10.0; Level II, inconclusive evidence)” and 13: “The
duration of acute n-3 PUFAs treatment could be extended to include
maintenance treatment to potentially prevent recurrence (8.36/10.0; Level
II, inconclusive).”),” and “Special Populations (questions 16–19: “N-3
PUFAs could be prescribed for MDD patients who are over-weight (BMI>
25) and/or have elevated levels of inflammatory markers (8.93/10.0; Level
II, inconclusive evidence);” “N3-PUFAs could be prescribed for women
with perinatal MDD (9.00/10.0; Level II, inconclusive evidence);” “N3-
PUFAs could be prescribed for elderly patients with MDD (8.79/10.0; Level
II, inconclusive evidence);” and “N3-PUFAs could be prescribed for chil-
dren and adolescents with MDD (8.71/10.0; Level II, inconclusive evi-
dence).”).”
Three main reasons may explain this consensus phenomenon. First,
it would be relatively difficult to conduct clinical trials addressing ei-
ther recurrence or prevention of depression, due to the high cost of such
studies; and more challenging to apply clinical pharmacotherapy trials
in the vulnerable populations such as pregnant women, the elderly and
Table 3
Consensus results and evidence of n-3 PUFAs clinical usage for MDD.
Themes Clinical questions Average score Supporting evidence
General Concepts 1 Clinicians who use n-3 PUFA treatments in major depressive disorder (MDD) should do so only after
applying a clinical interview to confirm the diagnosis and assess mental status and relevant physical
conditions, including fish hypersensitivities.
7.86 Level I
1 N-3 PUFAs are better used as an adjunctive treatment than monotherapy for adult MDD. 8.07 Level I
1 N-3 PUFAs are one of the potential adjunctive treatments for adult MDD. 9.43 Level I
1 N-3 PUFAs are one of the potential monotherapies for adult MDD. 5.93* Level II, inconclusive
1 N-3 PUFAs can be efficacious and safe, both for acceleration and augmentation.
*Acceleration = adding n-3 at the beginning of treatment concurrently with another
antidepressant.*Augmentation = adding n-3 when a prior antidepressant's effect is inadequate.
8.29 Level I
1 Both pure EPA and EPA/DHA (ratio≥2:1) combinations are effective as a potential treatment of MDD. 8.79 Level I
1 Pure EPA is more recommended than EPA/DHA (>2) combination. 6.57* Level II, inconclusive
Acute Treatment Strategy 1 The recommended therapeutic dosages should aim for 1 g/day to 2 g/day of total EPA from pure EPA or
1 g/day to 2 g/day EPA from an EPA/DHA (≥2:1) combination.
8.86 Level I
1 The dose is recommended to be increased in 2 weeks for non- or partial responders, and titrated up to the
maximum dose in 4–6 weeks if tolerable.
7.14 Level I
1 For non-responders, it is recommended to evaluate the quality of n-3 PUFA supplementary products. 7.64 Level II
Recurrence and
Prevention
1 N-3 PUFAs could be recommended as a potential prophylactic treatment for high-risk populations
(alongside standard medical care).
7.50 Level II, inconclusive
1 N3-PUFAs are considered similarly effective for recurrent MDD, compared with treatment-naïve MDD, as
an adjunctive treatment.
6.86* Level II, inconclusive
1 The duration of acute n-3 PUFAs treatment could be extended to include maintenance treatment to
potentially prevent recurrence.
8.36 Level II, inconclusive
Safety 1 It is recommended to monitor adverse effects systematically, including the gastrointestinal and
dermatological conditions, and obtaining a comprehensive metabolic panel in patients receiving higher
doses of n-3 PUFAs.
8.07 Level I
1 If clinicians are not familiar with high quality n-3 PUFAs in the market, they should consider prescription
omega-3 fatty acid products (RxOM3FAs).
8.29 Level IV
Special Populations 1 N-3 PUFAs could be prescribed for MDD patients who are over-weight (BMI> 25) and/or have elevated
levels of inflammatory markers.
8.93 Level II, inconclusive
1 N3-PUFAs could be prescribed for women with perinatal MDD. 9.00 Level II, inconclusive
1 N3-PUFAs could be prescribed for elderly patients with MDD. 8.79 Level II, inconclusive
1 N3-PUFAs could be prescribed for children and adolescents with MDD. 8.71 Level II, inconclusive
⁎ Did not reached the predefined consensus level (>7.0). **Please refer to the ISNPR guideline for full references of evidence.
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children, and thus the treatment choices and evidence of even phar-
macotherapy are scarce in these domains and populations, that treat-
ment decisions are often guided by data from general adults in acute
treatment settings (Taylor, 2014). Second, becauseof the “placebo-like”
tolerability and safety profile of n-3 PUFAs (Chang et al., 2018a), it
could be justified to use n-3 PUFAs in the elderly, children and pregnant
women if adequate dosage was prescribed, and careful selection of the
patients, such as overweight (BMI> 25) and/or have elevated levels of
inflammatory markers was done before the treatment. In fact, taking
the elderly for example, one meta-analysis included nine studies sug-
gested that overall, antidepressant effects of n-3 PUFA was not sig-
nificant for older adults, (Bai et al., 2018), however, it also found that if
the dosage of n-3 PUFA is greater than 1.5 g/d, the therapeutic effects
could be significant. This phenomenon was further enhanced when sub-
categorizing the elderly into well-being mental health group and de-
pressive group in another meta-analysis (Bae and Kim, 2018), and was
similar in studies of adult populations, suggestive of the importance of
adequate dosing and patient selection (Lin et al., 2012). Finally, al-
though therapeutic efficacy associated with recurrence and prevention
is not yet well demonstrated, when we consider, say, pregnant women,
if we take into account the entire clinical context, i.e., potential ob-
stetrical benefits (Freeman et al., 2014), the expert consensus supports
n-3 PUFAs remaining in the treatment armamentarium. This highlights
the value of the Delphi process in research translation, by bridging the
gaps between evidence and practice, and by reframing research evi-
dence in relevant fields and presenting the evidence to both clinicians
and patients.
4.3. Strengths and limitations
As our Delphi survey is clinically-oriented, a major limitation is the
shortage of data addressing unanswered questions, such as utility in
special populations and the basic biological research data on the anti-
depressant mechanism of n-3 PUFAs. However, as most of the panelists
are familiar with both clinical MDD management and basic n-3 PUFAs
research, the consensus represents a balance between knowledge from
clinical trial and preclinical evidence, and from clinical practice. For
example, some of the consensus items, such as “N-3 PUFAs could be
prescribed for MDD patients who are overweight (BMI> 25) and/or have
elevated levels of inflammatory markers,” are originally formulated based
on both clinical (Rapaport et al., 2016) and basic research results
(Song et al., 2016; Su, 2009; Su et al., 2014), and there are ongoing
studies trying to bridge basic research and clinical practice (e.g. using
EPA monotherapy in overweight patients with MDD and elevated CRP
at baseline, NCT02553915). As such, we believe this supports future
actions to translate mechanistic results into clinical practice. Another
key limitation also recognized is that this study surveyed academics
with an interest in n-3 PUFAs, and as such, their views may be more
positive towards n-3 PUFAs than those of expert clinicians without such
an interest.
5. Conclusions
There is still inconsistency and heterogeneity in the literature re-
garding 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 insufficiencies in the extant clinical research.
6. 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 either presentation honoraria, travel
support, clinical trial grants, book royalties, or independent con-
sultancy payments from: Integria Healthcare & MediHerb, Pfizer, Scius
Health, Key Pharmaceuticals, Australian Natural Therapies Group, Fiji
Kava, Taki Mai, FIT-BioCeuticals, Blackmores, Soho-Flordis,
Healthworld, HealthEd, HealthMasters, Kantar Consulting, Grunbiotics,
Australian Natural Therapeutics Group, Research Reviews, Elsevier,
Chaminade University, International Society for Affective Disorders,
Complementary Medicines Australia, SPRIM, Terry White Chemists,
ANS, Society for Medicinal Plant and Natural Product Research, Sanofi-
Aventis, Omega-3 center, the National Health and Medical Research
Council, CR Roper Fellowship
Felice Jacka has received Grant/Research support from the Brain
and Behavior Research Institute, the National Health and Medical
Research Council (NHMRC), Australian Rotary Health, the Geelong
Medical Research Foundation, the Ian Potter Foundation, Eli Lilly, Meat
and Livestock Australia, The A2 Milk Company, BeFit Foods,
Woolworths Limited, Fernwood Foundation, The Wilson Foundation,
and The University of Melbourne and has received speakers honoraria
from Sanofi-Synthelabo, Janssen Cilag, Servier, Pfizer, Health Ed,
Network Nutrition, Angelini Farmaceutica, Eli Lilly and Metagenics.
She is supported by an NHMRC Career Development Fellowship (2)
(#1108125). Felice Jacka has written two books for commercial pub-
lication and has a personal belief that good diet quality is important for
mental and brain health. Matsuoka has received honoraria for speaking
from Suntory Wellness, Pfizer, Mochida, Eli Lilly, Morinaga Milk, and
NTT Data.
7. 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 manu-
script, 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 inter-
pretation 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 and
DMR-109-102 from the China Medical University Hospital, Taichung,
Taiwan. In addition, Michael Berk is supported by a NHMRC Senior
Principal Research Fellowship (1059660 and APP1156072) and Jerome
Sarris is supported by an NHMRC Clinical Research Fellowship
(APP1125000). We thank Miss Yu-Chuan Chien from University of
T.-W. Guu, et al. Journal of Affective Disorders 265 (2020) 233–238
237
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Macau, China (MYRG2018-00242-ICMS) for data collection and orga-
nization.
Supplementary materials
Supplementary material associated with this article can be found, in
the online version, at doi:10.1016/j.jad.2020.01.050.
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https://doi.org/10.1016/j.jad.2020.01.050
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	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
	Introduction
	Methods
	Panel formation
	Literature review and questionnaire development
	Delphi method
	Data analyses
	Results
	Panel members
	Agreement of n-3 PUFAs clinical usage for MDD
	Discussion
	Differences between consensus degree and practice
	Heterogeneity in the evidence
	Strengths and limitations
	Conclusions
	Disclosures
	Author contributions
	Role of the funding source
	mk:H1_18
	Acknowledgements
	Supplementary materials
	References