SAM-e Treatment of Depression in Parkinson's Disease

SAM-e 治疗帕金森病抑郁症

• 批准号: 6541454
• 负责人: Alessandro DiRocco
• 金额: $ 86.19万
• 依托单位: BETH ISRAEL MEDICAL CTR (NEW YORK)
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-20 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6541454
• 关键词: Parkinson's disease; S adenosylmethionine; alternative medicine; antidepressants; behavioral /social science research tag; catechol methyltransferase; citalopram; clinical research; cognition; depression; diet therapy; dietary supplements; drug screening /evaluation; gene mutation; genetic polymorphism; genotype; human subject; human therapy evaluation; medical complication; memory; mental disorder chemotherapy; neuropsychology; nutrition related tag; placebos; psychomotor function; serotonin inhibitor; transmethylation

DESCRIPTION (provided by applicant): S-Adenosyl-methionme (SAM-e) is a molecule present in all eukaryotic cells, where it serves as the methyl-group donor for a number of metabolic functions. In the nervous system, SAM-E is essential in the metabolism of cathecholamines and may play an essential role in receptor stabilization and myelin formation and repair. SAM-a is available in the USA as a food supplement and is promoted as a mood enhancer. Parkinson's disease (PD) is commonly associated with depression, but conventional antidepressants have limited efficacy in parkinsonian patients and may exacerbate motor symptoms. SAM-a improves dopamine transmission, may have a beneficial effect on dopamine receptors and may be a good alternative to the currently used antidepressants. We have conducted a ten-week pilot study of SAM-e in thirteen depressed patients with PD. All patients had been previously treated with other anti-depressant agents and had no significant benefit or had intolerable side effects. Eleven patients completed the study, and ten had at least a 50% improvement of the 17point Hamilton Depression Scale (HAMD), while one patient did not improve. The mean HAMD score before SAM-e treatment was 27.09 greater than or equal to 6.04 SD), and was 9.55 +/-7.29 SD) after treatment (p<0.0001). Although uncontrolled and preliminary, the study suggests that SAM-e is well tolerated and may be a safe and effective alternative to other antidepressants used in PD. Therefore, we propose a controlled, double-blind study to investigate whether SAM-a is safe and effective in the treatment of depression associated with Parkinson's disease. The efficacy of SAM-e will be compared to placebo and to Citalopram, a Selective Serotonin Reuptake Inhibitor commonly used for the treatment of depression in PD. Secondary aims include investigating: a) the effect of SAM-e on the motor symptoms of PD; the effect of SAM-e on the serum concentrations of metabolites of the trans-methylation pathway; b) whether the clinical effect of SAM-e is associated with the presence of common genetic polymorphisms encoding enzymes of the trans-methylation pathway; and d) whether SAM-e treatment is associated with improvement in neuropsychological functioning. The submission of this application was previously discussed with officers of the National Center for Complementary and Alternative Medicine (NCCAM), who found the clinical and scientific scopes of this application compatible with the mission of their Institute, and recommended the submission of this grant proposal.

描述（由申请人提供）：S-腺苷 - 甲硫代（SAM-E）是存在于所有真核细胞中的一个分子，在该细胞中它是许多代谢功能的甲基组供体。在神经系统中，SAM-E在呼吸呼析的代谢中至关重要，并且可能在受体稳定和髓磷脂形成和修复中起着至关重要的作用。 SAM-A可以在美国作为食物补充剂提供，并作为情绪增强剂促进。 帕金森氏病（PD）通常与抑郁症有关，但是常规的抗抑郁药对帕金森病患者的疗效有限，可能会加剧运动症状。 SAM-A改善了多巴胺的传播，可能对多巴胺受体具有有益的作用，并且可能是当前使用的抗抑郁药的良好替代品。 我们已经在13例PD患者中对SAM-E进行了为期十周的SAM-E试点研究。 所有患者以前曾接受过其他抗抑郁药的治疗，没有明显的好处或无法忍受的副作用。 11名患者完成了这项研究，十名患者至少提高了17点汉密尔顿抑郁量表（HAMD）50％，而一名患者没有改善。 在治疗后，SAM-E治疗前的平均HAMD分数大于或等于6.04 SD，而处理后为9.55 +/- 7.29 SD（P <0.0001）。 尽管不受控制和初步研究表明，SAM-E的耐受性良好，并且可能是PD中其他抗抑郁药的安全有效替代品。因此，我们提出了一项受控的双盲研究，以研究SAM-A是否可以安全有效地治疗与帕金森氏病有关的抑郁症。 SAM-E的功效将与安慰剂和西妥位丙酰胺（一种选择性的5-羟色胺再摄取抑制剂，通常用于治疗PD中的抑郁症。 次要目的包括研究：a）SAM-E对PD运动症状的影响； SAM-E对反甲基化途径代谢产物的血清浓度的影响； b）SAM-E的临床作用是否与编码反甲基化途径酶的常见遗传多态性有关； d）SAM-E治疗是否与神经心理功能的改善有关。 该申请的提交先前与国家补充和替代医学中心（NCCAM）的官员进行了讨论，后者发现该申请的临床和科学范围与其研究所的使命兼容，并建议提交该赠款建议。