S-Adenosyl Methionine (SAMe) Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders With Major Depressive Disorder: A Double-Blind, Randomized Clinical Trial
Publication: American Journal of Psychiatry
Abstract
Objective
Despite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-adenosyl methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development.
Method
Participants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM–D).
Results
The HAM–D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively. There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively).
Conclusions
These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.
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History
Received: 21 August 2009
Accepted: 28 December 2009
Published online: 1 August 2010
Published in print: August 2010
Authors
Competing Interests
Dr. Papakostas has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Pfizer, Pierre Fabre Laboratories, Shire Pharmaceuticals, and Wyeth; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, Pamlab, Pfizer, Pierre Fabre Laboratories, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth; he has received research support from Bristol-Myers Squibb, Forest Pharmaceuticals, the National Institute of Mental Health, Pamlab, Pfizer, and Ridge Diagnostics (formerly known as Precision Human Biolaboratories); and he has served on the speaker's bureau for Bristol-Myers Squibb and Pfizer. Dr. Mischoulon has received research support for other clinical trials in the form of donated medications from Amarin (Laxdale), Bristol-Myers Squibb, Cederroth, Lichtwer Pharma GmbH, Nordic Naturals, and Swiss Medica; he has received consulting and writing honoraria from Pamlab; he has received speaking honoraria from Bristol-Myers Squibb, Nordic Naturals, Pfizer, Pamlab, and Virbac as well as from Reed Medical Education (a company working as a logistics collaborator for the Massachusetts General Hospital Psychiatry Academy); and he has received royalty income from Back Bay Scientific for PMS Escape (patent application pending). Dr. Alpert has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Cephalon, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, J and J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has participated on the advisory boards of or as a consultant to Eli Lilly, Pamlab, and Pharmavite; and he has received speaker's honoraria from Eli Lilly, Janssen, Organon, and Reed Medical Education. Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Bio Research, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, J and J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, the National Center for Complementary and Alternative Medicine, the National Institute on Drug and Alcohol Abuse, the National Institute of Mental Health, Novartis, Organon Inc., Pamlab, Pfizer, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Synthelabo, and Wyeth-Ayerst Laboratories; he has served on the advisory boards of or as a consultant to Abbott Laboratories, Amarin, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, BioMarin Pharmaceuticals, Biovail Pharmaceuticals, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Grunenthal GmbH Janssen Pharmaceutica, Jazz Pharmaceuticals, J and J Pharmaceuticals, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, PsychoGenics, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has received speaker and publishing fees from Advanced Meeting Partners, the American Psychiatric Association, AstraZeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, Massachusetts General Hospital Psychiatry Academy/Primedia, Massachusetts General Hospital Psychiatry Academy/Reed-Elsevier, UBC Pharma, and Wyeth-Ayerst Laboratories; he is a shareholder with Compellis; he has patent applications for sequential parallel comparison of design and for a combination of azapirones and bupropion in major depressive disorder; and he receives copyright royalties for the following Massachusetts General Hospital assessment tools: the Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, the Discontinuation-Emergent Sign and Symptom scale, and SAFER. Ms. Shyu reports no financial relationships with commercial interests.
Funding Information
Funded by a National Institute of Mental Health grant (5-K23 MH-069629).
SAMe and matching placebo pills were provided (free of cost) by Pharmavite.
The education programs conducted by the Massachusetts General Hospital Psychiatry Academy were supported through Independent Medical Education grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the Massachusetts General Hospital Psychiatry Academy are listed on the Academy's website (www.mghcme.org).
ClinicalTrials.gov registry number, NCT00093847.
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