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AJP CME: June 2016 - Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses

Activity Type:

  • Journal CME

Release Date: 6/1/2016

Expiration Date: 5/31/2018

  • AMA PRA Category 1 Physician: 1
  • Participation: 1

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Objective: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted.

Method: A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed.

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Educational Objective

The participant will describe how the application of nutraceuticals may be applied in the treatment of depression in combination with pharmacotherapy.

Target Audience

This program is designed for all psychiatrists in clinical practice, residents in Graduate Medical Education programs, medical students interested in psychiatry, and other physicians who wish to advance their current knowledge of clinical medicine.

Estimated Time to Complete

Duration: 1 hour
Begin Date: June 1, 2016
End Date: May 31, 2018

How to Earn Credit

In order to earn CME credit, subscribers should read through the material presented in the article. After reading the article, complete the course online at and submit your evaluation and study hours (up to 1 AMA PRA Category 1 Credit™).


The American Psychiatric Association (APA) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The APA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Faculty and Planner Disclosures

Title: Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses

Authors: Jerome Sarris, Ph.D., M.H.Sc., Jenifer Murphy, Ph.D., David Mischoulon, M.D., Ph.D., George I. Papakostas, M.D., Maurizio Fava, M.D., Michael Berk, M.D., Ph.D., Chee H. Ng, M.D.

Affiliations: From the Department of Psychiatry, the Melbourne Clinic, University of Melbourne, Melbourne, Australia (J.S., J.M., M. B., C.H.N.); the Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia (J.S.); the Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston (D.M., G.I.P., M.F.); the IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, Australia (M.B.); Orygen, the National Centre of Excellence in Youth Mental Health and the Centre of Youth Mental Health, Melbourne, Australia (M.B.); and the Florey Institute for Neuroscience and Mental Health, Melbourne, Australia (M.B.).

Disclosures: All authors except Dr. Murphy disclose having been provided previous or current research funding to study pharmaceuticals and nutraceuticals for mood disorders, including but not restricted to omega 3, folinic acid, 5-MTHF, tryptophan, and S-adenosylmethionine. Dr. Sarris reports no specific direct conflict of interest; general disclosures involve presentation honoraria, travel support, clinical trial grants, or book royalties from Integria Healthcare, MediHerb, Pfizer, Taki Mai, Pepsico, BioCeuticals, Blackmores, Soho-Flordis, Elsevier, HealthEd, and the National Health and Medical Research Council. Dr. Mischoulon has received research support from FisherWallace, Nordic Naturals, Methylation Sciences, and PharmoRx Therapeutics; he has received honoraria for consulting, speaking, and writing from the Massachusetts General Hospital Psychiatry Academy; and he has received royalties from Lippincott Williams & Wilkins for the book Natural Medications for Psychiatric Disorders: Considering the Alternatives. Dr. Papakostas has served as a consultant for Abbott, AstraZeneca, Avanir, Axsome (on behalf of Massachusetts General Hospital [MGH]), Brainsway, Bristol-Myers Squibb, Cephalon, Dey, Eli Lilly, Genentech (on behalf of MGH), GlaxoSmithKline, Evotec, H. Lundbeck, Inflabloc, Janssen Global Services (on behalf of MGH), Jazz Pharmaceuticals, Johnson & Johnson (on behalf of MGH), Methylation Sciences, Novartis, One Carbon Therapeutics (on behalf of MGH), Osmotica (on behalf of MGH), Otsuka, PAMLAB, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire, Sunovion, Taisho, Takeda, Theracos, and Wyeth; he has received honoraria (for lectures or consultancy) from Abbott, AstraZeneca, Avanir, Bristol-Myers Squibb, Brainsway, Cephalon, Dey, Eli Lilly, Evotec, Forest, GlaxoSmithKline, Inflabloc, Jazz, H. Lundbeck, Medichem, Meiji Seika, Novartis, Otsuka, PAMLAB, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire, Sunovion, Takeda, Theracos, Titan, and Wyeth; he has received research support (paid to hospital) from AstraZeneca, Bristol-Myers Squibb, Forest, the National Institute of Mental Health, Neuralstem, PAMLAB, Pfizer, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion, Tal Medical, and Theracos; he has also served (not currently) on the speaker’s bureau for Bristol-Myers Squibb and Pfizer. Dr. Fava has received research support from and/or served as an adviser or consultant to Acadia, Alkermes, AstraZeneca, Avanir, AXSOME Therapeutics, Biogen, Bristol-Myers Squibb, Cerecor, Dinippon Sumitomo, Eli Lilly, EnVivo, Euthymics Bioscience, Forest, FORUM, GenOmind, GlaxoSmithKline, Intracellular, Janssen R&D, Johnson & Johnson Pharmaceutical Research and Development, Lundbeck, Merck, Methylation Sciences, MSI Methylation Sciences, the National Center for Complementary and Alternative Medicine, the National Coordinating Center for Integrative Medicine, NIDA, NIMH, Naurex, Nestle Health Sciences, Neuralstem, Novartis, Nutrition 21, Osmotica, Otsuka, PamLab, Pfizer, PharmoRx Therapeutics, Photothera, PPD, Puretech Ventures, PsychoGenics, RCT Logic (formerly Clinical Trials Solutions), Reckitt Benckiser, Ridge Diagnostics, Roche, Sanofi-Aventis, Servier Laboratories, the Stanley Medical Research Institute, Sunovion, Taisho, Takeda, Tal Medical, and VistaGen; he has had speaking or publishing roles for the American Society of Clinical Psychopharmacology, Belvoir Media Group, CME Institute/Physicians Postgraduate Press, and MGH Psychiatry Academy; he has equity holdings in Compellis and PsyBrain; he is named on patents for sequential parallel comparison design, licensed by MGH to Pharmaceutical Product Development, and a patent application for a combination of ketamine plus scopolamine in major depressive disorder, licensed by MGH to Biohaven; and he is a copyright holder for the MGH Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms, the Symptoms of Depression Questionnaire, and SAFER and has publications with Lippincott Williams & Wilkins, Wolters Kluwer, and World Scientific Publishing. Dr. Berk has received grant/research support from Stanley Medical Research Foundation, MBF, NHMRC, NHMRC Senior Principal Research Fellowship (1059660), Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Rotary Health, Meat and Livestock Board, Woolworths, BeyondBlue, Geelong Medical Research Foundation, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma, and Servier; he has been a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Pfizer, Sanofi Synthelabo, Servier, Solvay, and Wyeth; he has been a consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Bioadvantex, Merck, Glaxo SmithKline, Lundbeck, Janssen Cilag, and Servier; and he is a co-inventor of two provisional patents regarding the use of NAC and related compounds for psychiatric indications, which, while assigned to the Mental Health Research Institute, could lead to personal remuneration upon a commercialization event. Dr. Ng has served on advisory boards for Servier, Wyeth, and Eli Lilly; has received research grant support from Wyeth and Lundbeck; and has received honoraria from Servier, Bristol-Myers Squibb, Organon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, AstraZeneca, Wyeth, and Pfizer. Dr. Murphy reports no financial relationships with commercial interests.

Discussion of unapproved or investigational use of products*: Yes.

*APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by scientific literature and clinical experience.

Program Planners

Robert Freedman, M.D. (Editor-in-Chief, AJP); Susan K. Schultz, M.D. (Deputy Editor, AJP); Michael D. Roy (Editorial Director, AJP) ; Michael A. Pogachar (Online Content Manager, Journals).

Dr. Schultz has received research support from the Alzheimer’s Disease Cooperative Study for projects conducted in partnership with Toyama Chemical Company and in partnership with Eli Lilly and Company. Dr. Freedman, Mr. Roy, and Mr. Pogachar report no financial relationships with commercial interests.

Hardware/Software Requirements

This internet-based CME activity is best experienced using Internet Explorer 8+, Mozilla Firefox 3+, Safari 4+. This Web site requires that JavaScript and session cookies be enabled. Certain activities may require additional software to view multimedia, presentation, or printable versions of the content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Adobe Acrobat, Microsoft PowerPoint, and Windows Media Player.

Optimal System Configuration:
Flash Player: Adobe Flash Player 10.1+ 
Browser: Firefox 3+, Internet Explorer 8.0+, Safari 4.0+, or Google Chrome 7.0+ 
Operating System: Windows XP+ or Mac OS X 10.4+ 
Internet Connection: 1 Mbps or higher
Screen Resolution: 1024 x 768 pixels.

Minimum Requirements:
Windows PC:
500-MHz Pentium II; Windows XP or higher; 128 MB RAM; Video Card at least 64MB of video memory; Sound Card at least 16-bit; Macromedia Flash Player 10 or higher, audio playback with speakers for programs with video content; Firefox 1.1+, Internet Explorer 7.0+, Safari 1.0+, Google Chrome, or Opera
Mac OS X 10.3 or higher with latest updates installed; 1.83MHz Intel Core Duo or faster; RAM: 128MB or more; Video Card: at least 64MB of video memory; Sound Card: at least 16-bit

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