In vivo cardiovascular effects of the new atypical neuroleptic sertindole

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

Method: 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).

Results: 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.

Conclusion: 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).