Benkert O, Szegedi A, Wetzel H, Staab H J, Meister W, Philipp M
Department of Psychiatry, University of Mainz, Germany.
Acta Psychiatr Scand. 1997 Apr;95(4):288-96. doi: 10.1111/j.1600-0447.1997.tb09634.x.
In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n = 86; maprotiline group, n = 88) were again randomized to either continuation of the previous dosage (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.
鉴于缺乏关于选择性5-羟色胺再摄取抑制剂（SSRI）帕罗西汀剂量递增益处的对照前瞻性研究，我们开展了一项双盲、随机、平行组多中心研究，旨在根据改良的研究诊断标准（RDC），比较帕罗西汀和马普替林剂量递增对治疗反应不足的重度或轻度抑郁症患者可能带来的益处。研究样本包括544例不同抑郁严重程度的门诊患者。患者在最初3周以双盲方式接受20mg帕罗西汀（n = 271）或100mg马普替林（n = 273）治疗。3周后的反应根据明确的操作性标准进行定义。治疗反应不足的患者（帕罗西汀组，n = 86；马普替林组，n = 88）再次随机分为继续使用先前剂量（帕罗西汀，n = 36；马普替林，n = 48）或增加剂量，即分别为40mg帕罗西汀（n = 50）或150mg马普替林（n = 40）。进行了意向性治疗分析和完成者分析。将反应定义为汉密尔顿抑郁量表（17项版本）（HAMD-17）评分较基线至少降低50%，结果发现帕罗西汀或马普替林剂量递增均无显著益处。根据抑郁基线严重程度分层也未显示剂量递增有显著益处。剂量递增后，低剂量治疗期间未出现的新不良事件很少发生。我们的结果支持以下观点，即20mg帕罗西汀剂量对大多数抑郁症患者的急性治疗是最佳的。
