ABSTRACT
INTRODUCTION: The intensity (loudness)-dependent amplitude change (IDAP) of auditory evoked event-related potential (ERP) components has been suggested as an indicator of central serotonergic neurotransmission. In patients with major depression, associations of high IDAP with favorable SSRI treatment outcome have been reported. This is the first study to assess the predictive value of the IDAP in SNRI treatment. METHODS: We evaluated the pre-treatment intensity-dependent change of auditory evoked P1, N1, P2, and P1/N1 and N1/P2 peak-to-peak amplitudes in 14 inpatients with major depressive episode (DSM IV) in the course of 24 days of treatment with the SNRI reboxetine (6-12 mg/d). RESULTS: Our data revealed a highly significant correlation between lower intensity-dependent N1 amplitude slopes prior to reboxetine treatment and stronger decrease of HDRS total score at Fz ( r = 0.86, P < 0.001), Fcz ( r = 0.91, P < 0.001), and Cz ( r = 0.93, P < 0.001). CONCLUSION: This result corroborates the hypothesis of the IDAP as a differential indicator of serotonergic versus noradrenergic antidepressant psychopharmacotherapy.
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Evoked Potentials, Auditory/physiology , Morpholines/therapeutic use , Acoustic Stimulation/methods , Adult , Depressive Disorder, Major/physiopathology , Dose-Response Relationship, Radiation , Electrodes , Electroencephalography , Evoked Potentials, Auditory/drug effects , Evoked Potentials, Auditory/radiation effects , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Reboxetine , Statistics as Topic , Time Factors , Treatment OutcomeABSTRACT
As part of a prospective clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function (ANF), serial standardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability (HRV) were obtained from 51 medication-free inpatients with schizophrenia (DSM-III-R-diagnosed) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day (N = 12), olanzapine 20 mg/day (N = 13), sertindole 12 mg/day (N = 13), or clozapine 100 mg/day (N = 13). Reference values for the HRV data were obtained from a large group of well-matched healthy controls (N = 70). The most important findings were the following: (1) clozapine, olanzapine, and sertindole all prolonged mean frequency-corrected QTc times, which, in the case of sertindole, proved to be significant (Wilcoxon test p <0.05); (2) sertindole and clozapine significantly increased the mean resting heart rate; and (3) only clozapine significantly reduced the parasympathetic resting tone. The results of the HRV studies are discussed considering the in vitro receptor profiles of the atypical neuroleptics under study. Potential implications for the cardiac safety and tolerance of these drugs are also discussed.
Subject(s)
Antipsychotic Agents/pharmacology , Autonomic Nervous System/drug effects , Heart/drug effects , Pirenzepine/analogs & derivatives , Sulpiride/analogs & derivatives , Adult , Amisulpride , Autonomic Nervous System/physiology , Benzodiazepines , Clozapine/pharmacology , Electrocardiography/drug effects , Female , Heart Rate/drug effects , Humans , Imidazoles/pharmacology , Indoles/pharmacology , Male , Middle Aged , Olanzapine , Pirenzepine/pharmacology , Prospective Studies , Sulpiride/pharmacologyABSTRACT
BACKGROUND: Major depression (MD) is associated with an augmented risk of cardiovascular mortality. One possible explanation for this association is that MD influences autonomic neurocardiac regulation (ANR). However, previous studies on this subject revealed conflicting results. METHODS: Using an autonomic test battery, which consisted of standardised measurements of heart rate variability (HRV) and blood pressure, we (1) compared ANR between 25 patients with DSM-III-R diagnosed MD and 60 healthy controls, and (2) investigated the autonomic effects of antidepressive treatment with nefazodone. RESULTS: Following multivariate analysis of all tests a significant reduction in HRV could only be shown for the Valsalva ratio amongst the depressives compared to controls. There was a significant inverse correlation between the HRV during deep respiration and both the severity of depression and the duration of the depressive episode. Serial HRV recordings revealed that both the mean resting heart rate and systolic blood pressure significantly decreased after 21 days of nefazodone treatment (average dosage 413 mg/day), whereas after 10 days (average dosage 270.8 mg/day) there were no striking changes compared to the pre-treatment values. During nefazodone treatment no significant changes in parasympathetic tone occurred. LIMITATIONS: ANR was not assessed in a randomised, placebo-controlled fashion. CONCLUSIONS: (1) Patients with MD may suffer from functional disturbances in the interaction between the sympathetic and parasympathetic autonomic tree. (2) The pattern of autonomic changes during treatment suggests that nefazodone induced a dose dependent, serotonergically-mediated down-regulation of the sympathetic tone. This mechanism might be responsible for nefazodone's properties of reducing anxiety.
