Differential Prediction of First Clinical Response to Serotonergic and Noradrenergic Antidepressants Using the Loudness Dependence of Auditory Evoked Potentials in Patients With Major Depressive Disorder

Georg Juckel, M.D., Ph.D.; Oliver Pogarell, M.D.; Holger Augustin, M.D.; Christoph Mulert, M.D.; Florian Müller-Siecheneder, M.D.; Thomas Frodl, M.D., Ph.D.; Paraskevi Mavrogiorgou, M.D.; and Ulrich Hegerl, M.D., Ph.D.

Objective: 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.

Method: 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.

Results: 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. Nonresponders to citalopram or reboxetine showed the inverse LDAEP characteristics, respectively.

Conclusion: 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.

(J Clin Psychiatry 2007;68:1206-1212)

Received April 15, 2006; accepted Dec. 7, 2006. From the Department of Psychiatry, Ruhr-University Bochum, Bochum (Drs. Juckel and Mavrogiorgou), and the Department of Psychiatry, Ludwig Maximilians University of Munich, Munich (all authors), Germany.

This study was supported by the German Ministry for Education and Research with the promotional emphasis "German Research Network on Depression" (Project 6.3) and by an unrestricted grant from the Pharmacia-Upjohn Co. (investigator-initiated trial).

We thank Catherine Aubel, M.A., for her valuable help in the preparation of the manuscript. Ms. Aubel has no potential conflicts of interest in relation to this article.

The authors report no additional financial or other affiliations that can be considered a conflict of interest relevant to the subject of this article.

Corresponding author and reprints: Georg Juckel, M.D., Ph.D., Westphalian Center Bochum, Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Ruhr-University Bochum, Alexandrinenstrasse 1, 44791 Bochum, Germany (e-mail: juckelgwk@aol.com).