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.

No abstract

These preliminary findings are compatible with the hypothesis that inhibition of brain NE reuptake by reboxetine resulted in an inhibition of central noradrenergic activity via a local increase of NE concentration at inhibitory alpha(2)-autoreceptors. Long-term treatment (21 days) may cause desensitization and down-regulation of alpha(2)-autoreceptors, so that attenuation of the inhibitory restraint on sympathetic outflow results.

Background and Aim: Repetitive transcranial magnetic stimulation (rTMS) is supposed to be not as effective in severe depression as it is in medium depression. We evaluated the treatment response to an ultra-high-frequency (UHF; 30 Hz) approach, which was used to maximize the rTMS efficacy in severely ill patients. Methods: 43 severely depressed patients were included in the randomized, double-blind study and received either rTMS with 30 Hz over the left dorsolateral prefrontal cortex or sham condition for 3 weeks as an add-on therapy to stable antidepressant medication. Hamilton Depression Rating Scale (HDRS) and cognitive performance were evaluated before and after the intervention. Results: In the active UHF group, the HRDS score was reduced by about 7.2, whereas the sham condition showed a smaller reduction of the HDRS score with 3.9. However, lithium as a covariant was responsible for the outcome difference, not the group of stimulation. No adverse events were reported. Comparing the differences of both groups in the pre- and post-study performance in a trail-making test, a group effect for the UHF group that was not influenced by the lithium intake was observed. Conclusion: A 30-Hz left prefrontal rTMS in severely depressed patients was safe and no adverse events occurred. Due to a strong effect of lithium as a covariate, we could not demonstrate favorable antidepressant effects of the UHF stimulation compared to sham. However, we found an improvement of processing speed performance in the UHF group, which covaried with improvement of psychomotor retardation.