Massachusetts General Hospital, Boston, MA 02114, USA.
J Clin Psychiatry. 2012 Jun;73(6):843-8. doi: 10.4088/JCP.11m07139. Epub 2012 May 15.
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.
通过检查来自 73 名患者中的 35 名患者的血浆水平，来描述 S-腺苷甲硫氨酸（SAMe）对同型半胱氨酸的影响，以及潜在的不良心血管作用的风险，这些患者参与了 2010 年发表的一项为期 6 周的、针对接受选择性 5-羟色胺再摄取抑制剂（SSRIs）治疗但部分缓解的、伴有 DSM-IV 重性抑郁障碍（MDD）的患者的 SAMe 增效作用的随机、双盲、安慰剂对照试验。
2004 年 6 月 4 日至 2008 年 8 月 8 日，患者被随机分配到辅助安慰剂或 SAMe 800-1600mg/d 治疗 6 周。主要观察指标包括在每个治疗臂内（通过配对 t 检验）和治疗臂之间（通过独立样本 t 检验）的一碳循环中间产物的变化。采用单因素方差分析和 Fisher 保护最小显著差异进行比较，以比较每个一碳循环中间产物的治疗后水平。次要观察指标包括通过线性回归（针对汉密尔顿抑郁评定量表评分的变化）和逻辑回归（针对反应或缓解），检查临床改善与血浆中间产物水平变化之间的关系。
我们发现 SAMe 组和安慰剂组之间的预处理血浆总同型半胱氨酸（tHCY）水平存在显著差异（P=0.03）。经过 6 周的治疗后，SAMe 组的血浆 SAMe（P=0.002）和 SAH（P＜0.0001）水平显著升高；安慰剂组的中间产物无明显变化。SAMe 组和安慰剂组之间的治疗后血浆 SAMe（P=0.0035）、SAH（P＜0.0001）和 tHCY（P=0.0016）水平差异有统计学意义。未发现血浆中间产物水平与临床改善、反应或缓解之间存在显著相关性。
尽管对 SAMe 治疗可能对同型半胱氨酸水平和不良心血管作用风险的影响存在担忧，但治疗后 tHCY 水平无显著升高表明，不应期望 SAMe 产生毒性作用。然而，我们的发现存在一些显著的局限性，应谨慎解释。
ClinicalTrials.gov 标识符：NCT00093847。
