Stewart J W, Quitkin F M, McGrath P J, Amsterdam J, Fava M, Fawcett J, Reimherr F, Rosenbaum J, Beasley C, Roback P
Department of Psychiatry, New York State Psychiatric Institute, New York, USA.
Arch Gen Psychiatry. 1998 Apr;55(4):334-43. doi: 10.1001/archpsyc.55.4.334.
Delayed and persistent ("true drug") improvement characterizes the response to antidepressant medication. Early or nonpersistent ("placebo") benefit is typical of a placebo response. The prediction was that patients with a true drug response would sustain their benefit best if they continued to receive the drug and that patients with a placebo response would have an equivalent prognosis whether they continued to receive the drug or were switched to placebo.
Patients with major depression who met the study's response criteria (a modified Hamilton Depression Rating Scale score < or =7 and failure to meet major depression criteria after each of the last 3 weeks following 12 to 14 weeks of treatment with fluoxetine hydrochloride, 20 mg/d) were enrolled in a 50-week randomized placebo substitution trial during which the return of depressive symptoms defined relapse. The timing and persistency of response during initial treatment defined true drug or placebo response patterns.
Patients with a true drug response pattern relapsed significantly more frequently if they were switched to placebo than if they continued to receive fluoxetine (P<.001 for weeks 12-26, P<.005 for weeks 26-50, and P<.41 for weeks 50-62). Patients with a placebo response pattern had an equivalent outcome whether maintained on fluoxetine therapy or placebo (P< .20 for weeks 12-26, test invalid for weeks 26-50, and P<.67 for weeks 50-62). Patients with a placebo response pattern relapsed more often when they continued to receive fluoxetine than patients with a true drug response pattern (P<.01 for weeks 12-26, P<.10 for weeks 26-50, and P<.36 for weeks 50-62).
These findings confirm that pattern analysis validly differentiates true drug from nonspecific initial responses and extend its use to the continuation and maintenance phases of treatment for depression. Investigations into the mechanisms of antidepressant activity might best be limited to those that can account for delayed efficacy. Fluoxetine's efficacy during the continuation and maintenance phases of treatment may be limited to patients with a true drug pattern of initial response.
延迟且持续（“真正的药物”）改善是对抗抑郁药物反应的特征。早期或非持续性（“安慰剂”）获益是安慰剂反应的典型表现。预测是具有真正药物反应的患者如果继续接受药物治疗，其获益维持得最好；而具有安慰剂反应的患者，无论继续接受药物治疗还是换用安慰剂，其预后相当。
符合研究反应标准（使用20mg/d盐酸氟西汀治疗12至14周后，改良汉密尔顿抑郁量表评分≤7且在最后3周的每一周均不符合重度抑郁标准）的重度抑郁症患者参加了一项为期50周的随机安慰剂替代试验，在此期间抑郁症状的复发定义为病情复发。初始治疗期间反应的时间和持续性定义了真正的药物或安慰剂反应模式。
具有真正药物反应模式的患者，如果换用安慰剂，其复发频率显著高于继续接受氟西汀治疗的患者（第12 - 26周P<0.001，第26 - 50周P<0.005，第50 - 62周P<0.41）。具有安慰剂反应模式的患者，无论维持氟西汀治疗还是使用安慰剂，其结果相当（第12 - 26周P<0.20，第26 - 50周检验无效，第50 - 62周P<0.67）。具有安慰剂反应模式的患者继续接受氟西汀治疗时，比具有真正药物反应模式的患者复发更频繁（第12 - 26周P<0.01，第26 - 50周P<0.10，第50 - 62周P<0.36）。
这些发现证实模式分析能有效区分真正的药物反应与非特异性初始反应，并将其应用扩展至抑郁症治疗的延续和维持阶段。对抗抑郁活性机制的研究可能最好局限于那些能解释延迟疗效的机制。氟西汀在治疗延续和维持阶段的疗效可能仅限于具有真正药物初始反应模式的患者。
