Juckel Georg, Pogarell Oliver, Augustin Holger, Mulert Christoph, Müller-Siecheneder Florian, Frodl Thomas, Mavrogiorgou Paraskevi, Hegerl Ulrich
Department of Psychiatry, Ruhr-University Bochum, Bochum, Germany.
J Clin Psychiatry. 2007 Aug;68(8):1206-12. doi: 10.4088/jcp.v68n0806.
Predictors of treatment response to serotonergic versus nonserotonergic, e.g., noradrenergic, antidepressants are of considerable clinical relevance as they could help to reduce the occurrence of patients' receiving weeks or even months of unsuccessful treatment. Several studies show that the response to selective serotonin reuptake inhibitors can be successfully predicted by using the loudness dependence of auditory evoked potentials (LDAEP), which denotes change in the amplitudes in response to different stimulus intensities and is to date one of the best validated indicators of the central serotonergic system. The aim of the current randomized prospective study was to investigate whether or not LDAEP also allows the differential prediction of treatment response to serotonergic versus noradrenergic antidepressants.
Electrophysiologic recordings were performed on 48 subjects between 1999 and 2001. After exclusions due to artifacts, the study sample consisted of 35 unmedicated inpatients with a DSM-IV or ICD-10 diagnosis of major depressive disorder (mean +/- SD age = 42.5 +/- 10.8 years; 13 male, 22 female; mean +/- SD score of 28.9 +/- 5.7 on the Hamilton Rating Scale for Depression [HAM-D], the primary measure for psychopathology). The patients were then treated for 4 weeks with either the selective serotonin reuptake inhibitor citalopram or the noradrenaline reuptake inhibitor reboxetine.
Analysis of variance (F = 5.05, df = 1,31; p = .03) revealed that responders (50% improvement in HAM-D score) to the citalopram treatment were characterized by a strong LDAEP at baseline, and responders to reboxetine were characterized by a weak LDAEP at baseline. Non-responders to citalopram or reboxetine showed the inverse LDAEP characteristics, respectively.
This study is one of the first to demonstrate differential prediction of response to different classes of antidepressants. Patients at the beginning of an antidepressant treatment who show an initially strong LDAEP have a greater probability of responding to a serotonin-agonist antidepressant, whereas patients with a weak LDAEP will probably benefit more from a nonserotonergic, e.g., noradrenergic, antidepressant. If these results were replicated in a larger sample, this simple electroencephalographic method could be more broadly used in clinical practice to support clinicians in replacing the trial and error method with a more targeted and individualized approach to antidepressant treatment.
血清素能与非血清素能（如去甲肾上腺素能）抗抑郁药治疗反应的预测指标具有重要的临床意义，因为它们有助于减少患者接受数周甚至数月无效治疗的情况发生。多项研究表明，通过使用听觉诱发电位的响度依赖性（LDAEP）能够成功预测对选择性5-羟色胺再摄取抑制剂的反应，LDAEP指的是对不同刺激强度作出反应时振幅的变化，是迄今为止中枢血清素能系统最佳验证指标之一。本随机前瞻性研究的目的是调查LDAEP是否也能对血清素能与去甲肾上腺素能抗抑郁药的治疗反应进行差异预测。
1999年至2001年间，对48名受试者进行了电生理记录。排除因伪迹导致的数据后，研究样本包括35名未接受药物治疗的住院患者，他们被诊断为符合DSM-IV或ICD-10标准的重度抑郁症（年龄均值±标准差=42.5±10.8岁；男性13名，女性22名；汉密尔顿抑郁量表[HAM-D]的平均得分±标准差为28.9±5.7，这是精神病理学的主要测量指标）。然后，这些患者用选择性5-羟色胺再摄取抑制剂西酞普兰或去甲肾上腺素再摄取抑制剂瑞波西汀治疗4周。
方差分析（F = 5.05，自由度=1,31；p = 0.03）显示，西酞普兰治疗的反应者（HAM-D评分改善50%）在基线时LDAEP较强，瑞波西汀治疗的反应者在基线时LDAEP较弱。西酞普兰或瑞波西汀的无反应者分别表现出相反的LDAEP特征。
本研究是首批证明对不同类别抗抑郁药反应进行差异预测的研究之一。在抗抑郁治疗开始时，初始LDAEP较强的患者对血清素激动剂抗抑郁药有更大的反应可能性，而LDAEP较弱的患者可能从非血清素能（如去甲肾上腺素能）抗抑郁药中获益更多。如果这些结果能在更大样本中得到重复验证，这种简单的脑电图方法可在临床实践中更广泛地应用，以帮助临床医生用更有针对性和个性化的抗抑郁治疗方法取代试错法。
