Goldberg R J
Department of Psychiatry, Rhode Island Hospital, Brown University, Providence, USA.
Drugs Aging. 1997 Aug;11(2):119-31. doi: 10.2165/00002512-199711020-00004.
Depression is a significant problem in the elderly. Because of aging-related pharmacokinetic and pharmacodynamic changes, it is not possible to automatically extrapolate findings on the efficacy or tolerability of antidepressants from younger to older populations. Venlafaxine inhibits both noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake. Analysis of data from phase II and III trials showed that venlafaxine was comparably effective in the young and in a subset of over 350 elderly patients. Venlafaxine dosage needs to be lowered in the elderly with renal impairment. As a weak cytochrome P450 (CYP) inhibitor, it is unlikely to have clinically significant drug interactions. Venlafaxine may be associated with some increase in supine diastolic blood pressure, especially at dosages above 150 mg/day. Nefazodone is a serotonin uptake inhibitor and serotonin 5-HT2A receptor antagonist. Pooled analysis of about 250 patients found nefazodone to be effective in elderly individuals with moderate or severe depressive symptoms, with or without melancholia, in both primary and recurrent episodes. Nefazodone clearance is reduced in patients with hepatic impairment, and plasma concentrations have been reported to be higher in the elderly. Nefazodone is an inhibitor of the CYP3A4 family. There does not appear to be any increase in the frequency or severity of adverse effects in the elderly. Moclobemide is a selective inhibitor of monoamine oxidase type A. Studies in the elderly have found it to be well tolerated and meta-analysis has shown it to be comparably effective in young and elderly populations, and comparable to other antidepressants in terms of efficacy. Neither age nor renal impairment necessitate dosage adjustment, but hepatic impairment does necessitate dosage reduction. Dietary restrictions are not required. Overall, there is a relative paucity of data on the tolerability and efficacy of newer antidepressants in the elderly, especially those with concomitant medical disorders. Data that are available indicate that venlafaxine, nefazodone and moclobemide have comparable efficacy in older and younger patients.
抑郁症在老年人中是一个重大问题。由于与衰老相关的药代动力学和药效学变化，无法直接将抗抑郁药在年轻人群中的疗效或耐受性研究结果外推至老年人群。文拉法辛可抑制去甲肾上腺素和5-羟色胺（5-HT）的再摄取。对II期和III期试验数据的分析表明，文拉法辛在年轻人和350多名老年患者亚组中的疗效相当。肾功能受损的老年人需要降低文拉法辛的剂量。作为一种弱细胞色素P450（CYP）抑制剂，它不太可能产生具有临床意义的药物相互作用。文拉法辛可能会使仰卧位舒张压有所升高，尤其是剂量超过150毫克/天时。奈法唑酮是一种5-羟色胺摄取抑制剂和5-HT2A受体拮抗剂。对约250名患者的汇总分析发现，奈法唑酮对伴有或不伴有 melancholia的中度或重度抑郁症状的老年患者，无论是初发还是复发，均有效。肝功能受损患者的奈法唑酮清除率降低，据报道老年人的血浆浓度更高。奈法唑酮是CYP3A4家族的抑制剂。在老年人中，不良反应的频率或严重程度似乎没有增加。吗氯贝胺是一种选择性单胺氧化酶A型抑制剂。针对老年人开展的研究发现，它耐受性良好，荟萃分析表明，它在年轻人和老年人中的疗效相当，在疗效方面与其他抗抑郁药相当。年龄和肾功能受损均无需调整剂量，但肝功能受损确实需要减少剂量。无需饮食限制。总体而言，关于新型抗抑郁药在老年人，尤其是伴有其他疾病的老年人中的耐受性和疗效的数据相对较少。现有数据表明，文拉法辛、奈法唑酮和吗氯贝胺在老年患者和年轻患者中的疗效相当。
