S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder

A double-blind, randomized clinical trial

George I. Papakostas, David Mischoulon, Irene Shyu, Jonathan E. Alpert, Maurizio Fava

Research output: Contribution to journalArticle

139 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)942-948
Number of pages7
JournalAmerican Journal of Psychiatry
Volume167
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

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Major Depressive Disorder
Serotonin Uptake Inhibitors
Methionine
Antidepressive Agents
Randomized Controlled Trials
Placebos
Outcome Assessment (Health Care)
Numbers Needed To Treat
Therapeutics
Tissue Donors
Depression
Drug Therapy

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder : A double-blind, randomized clinical trial. / Papakostas, George I.; Mischoulon, David; Shyu, Irene; Alpert, Jonathan E.; Fava, Maurizio.

In: American Journal of Psychiatry, Vol. 167, No. 8, 08.2010, p. 942-948.

Research output: Contribution to journalArticle

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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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