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Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder.

ABSTRACT: To characterize the impact of S-adenosyl methionine (SAMe) on homocysteine and potential risk of adverse cardiovascular effects by examining plasma levels of SAMe, S-adenosyl homocysteine (SAH), total homocysteine (tHCY), methionine (MET), and 5-methyltetrahydrofolate (5-MTHF) in 35 of 73 patients from a 6-week randomized double-blind, placebo-controlled trial of SAMe augmentation in serotonin reuptake inhibitor partial responders with DSM-IV major depressive disorder (MDD), published in 2010.Subjects were randomized from June 4, 2004, until August 8, 2008, to adjunctive placebo or SAMe 800-1600 mg/d for 6 weeks. Primary outcome measures included changes in one-carbon cycle intermediates within each treatment arm (by paired t test) and between treatment arms (by independent samples t test). Univariate analysis of variance and Fisher Protected Least Significant Difference were carried out to compare posttreatment levels of each one-carbon cycle intermediate. Secondary outcome measures included associations between clinical improvement and change in plasma intermediate levels, examined by linear regression (for change in Hamilton Depression Rating Scale scores) and logistic regression (for response or remission).We found significant differences in pretreatment plasma levels of tHCY (P = .03) between the SAMe and placebo arms. Following 6 weeks of treatment, plasma SAMe (P = .002) and SAH (P < .0001) levels increased significantly in the SAMe arm; no intermediates in the placebo group changed significantly. Posttreatment plasma SAMe (P = .0035), SAH (P < .0001), and tHCY (P = .0016) levels differed significantly between the SAMe and placebo groups. No significant associations were found between plasma intermediate levels and clinical improvement, response, or remission.Despite concerns about the impact that SAMe therapy may have on homocysteine levels and risk of adverse cardiovascular effects, the lack of significant increase in tHCY levels after treatment suggests that no toxic effects from SAMe should be expected. Our findings, however, have some significant limitations and should be interpreted with caution.ClinicalTrials.gov identifier: NCT00093847.

SUBMITTER: Mischoulon D

PROVIDER: S-EPMC4156851 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder.

Mischoulon David D Alpert Jonathan E JE Arning Erland E Bottiglieri Teodoro T Fava Maurizio M Papakostas George I GI

The Journal of clinical psychiatry 20120515 6

<h4>Objective</h4>To characterize the impact of S-adenosyl methionine (SAMe) on homocysteine and potential risk of adverse cardiovascular effects by examining plasma levels of SAMe, S-adenosyl homocysteine (SAH), total homocysteine (tHCY), methionine (MET), and 5-methyltetrahydrofolate (5-MTHF) in 35 of 73 patients from a 6-week randomized double-blind, placebo-controlled trial of SAMe augmentation in serotonin reuptake inhibitor partial responders with DSM-IV major depressive disorder (MDD), pu ...[more]

PMID: 22687580

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Project description:BackgroundMajor depressive disorder (MDD) is a serious illness in children and adolescents. Vilazodone is a selective serotonin reuptake inhibitor approved for MDD in adults. This study evaluated the efficacy, safety, and tolerability of vilazodone in adolescent patients, ages 12-17 years, with MDD (NCT01878292).MethodsThis double-blind, randomized, placebo-controlled, parallel-group, fixed-dose study was conducted at 56 study centers in the United States and was 10 weeks in duration (a 1-week screening period, an 8-week double-blind treatment period, and a 1-week double-blind down-taper period). Outpatients with an MDD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria were included in the study. Clinical inclusion criteria required a Children's Depression Rating Scale-Revised (CDRS-R) total score of ≥ 40 and Clinical Global Impressions-Severity (CGI-S) score of ≥ 4. Patients were randomized 1:1:1 to 8 weeks of double-blind treatment with placebo (n = 174), vilazodone 15 mg/day (n = 175), or vilazodone 30 mg/day (n = 180). The primary and secondary efficacy parameters were change from baseline to week 8 in CDRS-R total score and CGI-S score, respectively. Safety parameters included adverse events (AEs); clinical laboratory, vital sign, and electrocardiogram parameters; and the Columbia-Suicide Severity Rating Scale.ResultsApproximately 86% of patients completed double-blind treatment. There was no statistically significant difference between vilazodone 15 mg/day or 30 mg/day and placebo in change from baseline in CDRS-R score. Change in CGI-S score was not significant after adjustment for multiple comparisons. The most common treatment-emergent AEs were nausea, upper abdominal pain, vomiting, diarrhea, nasopharyngitis, headache, and dizziness. Reports of suicidal ideation (placebo, 33.3%; vilazodone 15 mg/day, 36.0%; vilazodone 30 mg/day, 31.1%) and suicidal behavior (placebo, 1.8%; vilazodone 15 mg/day, 1.1%; vilazodone 30 mg/day, 1.1%) were similar between treatment groups. There were no deaths in the study.ConclusionsThe efficacy of vilazodone for the treatment of MDD in adolescent patients could not be confirmed in this study. Vilazodone was generally safe and well tolerated, with treatment-emergent AEs similar to those in adult patients.Clinical trial registrationNCT01878292.

Dataset Information

Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder.

Publications

Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder.

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