Tollefson G D, Birkett M, Koran L, Genduso L
Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, Ind. 46285.
J Clin Psychiatry. 1994 Oct;55 Suppl:69-76; discussion 77-8.
Recent advances in the pharmacotherapy of obsessive compulsive disorder (OCD) have led to a significant reduction in suffering and a return to productive living for many patients previously considered refractory to treatment. However, OCD can be a chronic disorder that significantly detracts from an individual's well-being. Potent inhibitors of 5-hydroxytryptamine (5-HT) reuptake have emerged as the first-line choice in the pharmacotherapy of OCD. These members of the therapeutic armamentarium for OCD, while associated with acute symptomatic improvement, have not been extensively studied during continuation therapy. In this study, 274 primary OCD subjects completed a 13-week, double-blind, placebo-controlled trial of three fixed doses of fluoxetine. Treatment responders (n = 76) continued their blinded treatment, whereas acute fixed-dose nonresponders began an open-label trial on their maximally tolerated dose (up to 80 mg daily) for 24 weeks. Responders maintained their acute treatment gains; in addition, all three doses of fluoxetine (20, 40, and 60 mg) were associated with further Y-BOCS improvement over the 24-week extension. Fluoxetine 60 mg achieved a statistically significantly greater reduction in Y-BOCS than placebo during the continuation. Open-label study subjects (n = 198) benefited from dose titration, with two thirds achieving a clinical response during the subsequent 24 weeks. Fluoxetine was well tolerated during both 24-week continuation periods. Only 4 (5.7%) of 70 subjects treated with fluoxetine in the responder extension terminated early due to an adverse event. The open-label extension, fluoxetine (to 80 mg), also demonstrated a low rate of adverse events; the profile of events was consistent with the extensive fluoxetine experience in other clinical populations. In conclusion, fluoxetine continuation treatment in OCD was associated with a maintained/improved symptomatic profile in most cases. Further dose titration improved the outcome of many acute, fixed-dose nonresponders. Continuation treatment with fluoxetine appeared to be well tolerated with few late-emergent adverse events.
强迫症（OCD）药物治疗的最新进展已使许多先前被认为难治的患者痛苦显著减轻，并恢复了有意义的生活。然而，OCD可能是一种慢性疾病，会严重损害个人的幸福感。5-羟色胺（5-HT）再摄取强效抑制剂已成为OCD药物治疗的一线选择。这些用于OCD治疗的药物，虽然与急性症状改善有关，但在维持治疗期间尚未得到广泛研究。在本研究中，274名原发性OCD受试者完成了一项为期13周、双盲、安慰剂对照试验，试验采用三种固定剂量的氟西汀。治疗有反应者（n = 76）继续接受盲法治疗，而急性固定剂量无反应者开始进行开放标签试验，服用其最大耐受剂量（每日高达80 mg），为期24周。有反应者维持了其急性治疗效果；此外，在24周的延长期内，所有三种剂量的氟西汀（20、40和60 mg）均与Y-BOCS进一步改善相关。在维持治疗期间，60 mg氟西汀在Y-BOCS降低方面比安慰剂有统计学意义上的显著更大幅度下降。开放标签研究受试者（n = 198）从剂量滴定中获益，三分之二的受试者在随后的24周内实现了临床反应。在两个24周的维持治疗期内，氟西汀耐受性良好。在有反应者延长期接受氟西汀治疗的70名受试者中，只有4名（5.7%）因不良事件提前终止治疗。开放标签延长期使用的氟西汀（至80 mg）也显示不良事件发生率较低；事件情况与氟西汀在其他临床人群中的广泛经验一致。总之，在大多数情况下，OCD患者使用氟西汀维持治疗与症状维持/改善相关。进一步的剂量滴定改善了许多急性固定剂量无反应者的治疗结果。氟西汀维持治疗似乎耐受性良好，晚期出现的不良事件很少。
