In vivo cardiovascular effects of the new atypical neuroleptic sertindole

The goal of this open clinical study was to perform a detailed investigation of the cardiovascular effects of the novel atypical neuroleptic sertindole.

Thirty initially untreated schizophrenic inpatients (diagnosed according to DSM-III-R) underwent a total of 103 serial recordings of standardized autonomic tests during a sertindole dose titration programme (4-16 mg/d). The autonomic test battery included: (1) conventional ECGs with 12 channels, (2) computer-assisted analysis of the 5-min resting heart rate variability (HRV); (3) HRV during standard autonomic reflex tests (deep breathing test, 30:15 ratio); and (4) blood pressure measurement under resting conditions and during orthostatic stress (Schellong test). Reference values for the HRV study were obtained from healthy controls ( n =80).

The most important findings were: (1) sertindole significantly increased the resting heart rate; (2) sertindole induced a significant and probably dose-dependent prolongation of the frequency-corrected QT-times, while mean PQ-conduction times remained unchanged; (3) sertindole had no significant effects on autonomic parasympathetic tone, both in the resting study and following the autonomic reflex tests; and (4) sertindole at doses between 4 and 16 mg/d did not significantly influence blood pressure either under resting conditions or during orthostatic stress.

The implications of these findings for the cardiovascular safety and tolerance of sertindole are discussed comprehensively, while considering the pathophysiologically relevant mechanisms underlying the appearance of life-threatening cardiac arrhythmias and sudden cardiac death. ( Int J Psych Clin Pract 2001; 5:33-40).