Zimmerman Mark, Thongy Tavi
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Rhode Island Hospital, Providence, USA.
J Clin Psychiatry. 2007 Aug;68(8):1271-6. doi: 10.4088/jcp.v68n0814.
A substantial number of patients who respond to antidepressants experience a relapse despite ongoing pharmacotherapy. The return of symptoms has been interpreted as a loss of the effectiveness of antidepressant activity. However, patients who initially improve while taking antidepressants include an admixture of true drug responders and placebo responders. Consequently, symptom return despite ongoing treatment may not represent a loss of drug effect because the patient may not have experienced a true drug response in the first place. The goal of the present report is to estimate the proportion of relapse attributable to the loss of true drug response versus a loss of placebo response.
We reviewed continuation studies of new-generation antidepressants that began as placebo-controlled acute-phase studies. Studies were identified using MEDLINE (English-language articles published from 1980 to 2005 in 23 prespecified journals, using the search terms depression, continuation, and tachyphylaxis). Finally, we identified studies in reference lists of pertinent studies and review articles.
Five studies were reviewed and selected according to the following criteria: continuation studies of new-generation antidepressants that began as placebo-controlled acute-phase studies. One of the studies was excluded from our analyses because it did not report response rates in the acute phase, and we could not find acute-phase response rates in related reports.
Using the 2 formulas proposed by Quitkin and colleagues, we estimated the proportion of relapse attributable to the loss of true drug response versus the loss of response attributable to the nonspecific effects of treatment: The relapse rate in placebo responders was 24.1%, whereas the relapse rate in antidepressant responders was 7.4%. Two different methods of estimating relapse suggested that the majority of relapses in patients taking antidepressants during continuation treatment could be attributed to relapses occurring in patients who were not true drug responders.
Most of the relapse rate during new-generation antidepressant continuation treatment may be due to relapse in patients who were not true drug responders, which suggests that loss of true drug response may be less common than previously thought.
相当一部分对抗抑郁药有反应的患者尽管持续接受药物治疗仍会复发。症状的复发被解释为抗抑郁活性有效性的丧失。然而，最初在服用抗抑郁药时病情有所改善的患者中，包括了真正的药物反应者和安慰剂反应者。因此，尽管持续治疗仍出现症状复发，可能并不代表药物效果丧失，因为患者最初可能并未经历真正的药物反应。本报告的目的是估计复发中因真正药物反应丧失与因安慰剂反应丧失所致的比例。
我们回顾了作为安慰剂对照急性期研究开始的新一代抗抑郁药的延续性研究。通过MEDLINE（1980年至2005年在23种预先指定的期刊上发表的英文文章，使用搜索词“抑郁”“延续性”和“快速耐受性”）来识别研究。最后，我们在相关研究和综述文章的参考文献列表中识别研究。
根据以下标准对五项研究进行了回顾和选择：作为安慰剂对照急性期研究开始的新一代抗抑郁药的延续性研究。其中一项研究被排除在我们的分析之外，因为它未报告急性期的反应率，且我们在相关报告中也未找到急性期反应率。
使用奎特金及其同事提出的两个公式，我们估计了因真正药物反应丧失导致的复发比例与因治疗非特异性效应导致的反应丧失比例：安慰剂反应者的复发率为24.1%，而抗抑郁药反应者的复发率为7.4%。两种不同的估计复发的方法表明，在延续性治疗期间服用抗抑郁药的患者中，大多数复发可归因于非真正药物反应者的复发。
新一代抗抑郁药延续性治疗期间的大多数复发率可能是由于非真正药物反应者的复发，这表明真正药物反应丧失可能比以前认为的更少见。
