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

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 electro-encephalographic 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.