Amsterdam Jay D, Shults Justine
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3309, United States.
J Affect Disord. 2009 May;115(1-2):234-40. doi: 10.1016/j.jad.2008.07.007. Epub 2008 Aug 9.
Tachyphylaxis often refers to the loss of antidepressant efficacy during long-term treatment. However, it may also refer to the gradual loss of efficacy after repeated antidepressant exposures over time. The aim of this study was to examine the phenomenon of tachyphylaxis in patients with Bipolar II major depression treated with either venlafaxine or lithium. We hypothesized that a greater number of prior antidepressant exposures would result in a reduced response to venlafaxine, but not lithium, therapy.
83 patients were randomized to treatment with either venlafaxine (n=43) or lithium (n=40). The primary outcome was a >or= 50% reduction in baseline Hamilton Depression Rating score. A detailed history of prior drug therapy was obtained. Logistic regression was used to test the hypothesis that prior antidepressant exposure was associated with reduced response to venlafaxine therapy.
The mean number of prior antidepressant and mood stabilizer exposures was significantly higher in venlafaxine non-responders versus responders (p=0.02). There was no significant association between response to lithium and the number of prior antidepressant and mood stabilizer exposures (p=0.38). The odds of responding to venlafaxine or lithium therapy decreased with an increasing number of prior antidepressant exposures (p=0.04). Response was not significantly affected by the number of prior mood stabilizer exposures (p=0.30). Adjustment for clinical and demographic covariates sharpened the estimated impact of prior antidepressant exposure on treatment outcome.
This study was a post hoc exploratory analysis. The study was not specifically powered to test the hypothesis of an association between number of prior antidepressant drug exposures and response to venlafaxine or lithium therapy.
These observations support earlier findings suggesting the presence of tachyphylaxis occurring after repeated antidepressant drug exposures. Possible mechanisms of tachyphylaxis may include genetic predisposition for non-response, physiological adaptation after repeated antidepressant exposures, and inherent illness and pharmacokinetic heterogeneity.
快速减敏通常指长期治疗期间抗抑郁药疗效丧失。然而，它也可能指随着时间推移反复接触抗抑郁药后疗效逐渐丧失。本研究的目的是探讨用文拉法辛或锂治疗的双相II型重度抑郁症患者中的快速减敏现象。我们假设既往更多次接触抗抑郁药会导致对文拉法辛治疗的反应降低，但对锂治疗无此影响。
83例患者被随机分为接受文拉法辛治疗组（n = 43）或锂治疗组（n = 40）。主要结局是汉密尔顿抑郁评定量表基线评分降低≥50%。获取了既往药物治疗的详细病史。采用逻辑回归检验既往抗抑郁药暴露与文拉法辛治疗反应降低相关的假设。
文拉法辛无反应者既往抗抑郁药和心境稳定剂暴露的平均次数显著高于有反应者（p = 0.02）。对锂的反应与既往抗抑郁药和心境稳定剂暴露次数之间无显著关联（p = 0.38）。随着既往抗抑郁药暴露次数增加，对文拉法辛或锂治疗有反应的几率降低（p = 0.04）。反应未受到既往心境稳定剂暴露次数的显著影响（p = 0.30）。对临床和人口统计学协变量进行调整后，既往抗抑郁药暴露对治疗结局的估计影响更加明显。
本研究是一项事后探索性分析。该研究并非专门为检验既往抗抑郁药暴露次数与对文拉法辛或锂治疗的反应之间存在关联这一假设而设计。
这些观察结果支持了早期研究结果，提示反复接触抗抑郁药后会出现快速减敏现象。快速减敏的可能机制可能包括无反应的遗传易感性、反复接触抗抑郁药后的生理适应，以及内在疾病和药代动力学异质性。
