Montgomery S A
Department of Psychiatry, St Mary's Hospital, London, UK.
Int Clin Psychopharmacol. 1995 Mar;10 Suppl 1:23-7. doi: 10.1097/00004850-199503001-00005.
Establishing the optimum therapeutic dose of a putative antidepressant is important to avoid unnecessarily high doses, which may be associated with increased frequency of severity of unwanted side effects, or too low a dose which may not achieve the best therapeutic effect. Flexible dose regimes that are often used in clinical trial programmes may lead to the use of too high a dose because of the attribution of response in depression to the higher dose used later in the study rather than being identified as a delayed response to a lower dose used earlier. Fixed dose studies provide a more reliable view of the dose response relationship and, where differences between doses are small, metanalysis of large databases may provide a useful tool for the establishing of the minimum therapeutic dose. Metanalysis of the placebo controlled results with citalopram demonstrated that the dose-response curves based on log odds ratios showed a very flat curve across the 20-60 mg range and that 20 mg appeared therefore to be the minimum effective dose. There was evidence that in some subgroups of depressed patients a better response may be seen with a higher dose. For example in patients with severe depression citalopram was effective compared with placebo in doses of both 20 mg and 40 mg. However there was a more pronounced therapeutic effect with the higher dose. Similar results have been reported with other selective serotonin reuptake inhibitors.
确定一种假定抗抑郁药的最佳治疗剂量非常重要，这样可以避免不必要的高剂量，因为高剂量可能会增加不良副作用的严重程度或发生频率，也可以避免剂量过低而无法达到最佳治疗效果。临床试验方案中常用的灵活剂量方案可能会导致使用过高的剂量，原因是将抑郁症的反应归因于研究后期使用的较高剂量，而不是被认定为对早期使用的较低剂量的延迟反应。固定剂量研究能更可靠地反映剂量反应关系，而且在剂量差异较小的情况下，对大型数据库进行荟萃分析可能会为确定最小治疗剂量提供有用的工具。对西酞普兰安慰剂对照结果的荟萃分析表明，基于对数优势比的剂量反应曲线在20 - 60毫克范围内呈非常平缓的曲线，因此20毫克似乎是最小有效剂量。有证据表明，在一些抑郁症患者亚组中，较高剂量可能会有更好的反应。例如，对于重度抑郁症患者，20毫克和40毫克剂量的西酞普兰与安慰剂相比均有效。然而，较高剂量的治疗效果更显著。其他选择性5-羟色胺再摄取抑制剂也有类似的结果报道。
