In vivo cardiovascular effects of the new atypical neuroleptic sertindole

INTRODUCTION: The goal of this open clinical study was to perform a detaile d investigation of the cardiovascular Effects of the novel atypical neurole ptic sertindole. METHOD: Thirty initially untreated schizophrenic inpatients (diagnosed acco rding to DSM-III-R) underwent a total of 103 serial recordings of standardi zed autonomic rests during a sertindole dose titration programme (4-16 mg/d ), The autonomic test battery included: (1) conventional ECGs with 12 chann els, (2) computer-assisted analysis of the 5-min resting heart rate variabi lity (HRV); (3) HRV during standard autonomic reflex rests (deep-breathing test, 30: 15 ratio); and (4) blood pressure measurement under vesting condi tions 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 inc reased the vesting heart rate; (2) sertindole induced a significant and pro bably dose-dependent prolongation of the frequency-corrected QT-times, whil e mean PQ-conduction times remained unchanged; (3) sertindole had no signif icant affects on autonomic parasympathetic tone, both in the vesting study and following the autonomic reflex tests; and (4) sertindole at doses betwe en 4 and 16 mg/d did not significantly influence blood pressure either unde r vesting conditions or during orthostatic stress. CONCLUSION: The implications of these findings for the cardiovascular safet y and tolerance of sertindole are discussed comprehensively, while consider ing the pathophysiologically relevant mechanisms underlying the appearance of life-threatening cardiac arrhythmias and sudden cardiac death.