What is the clinical evidence from this study?

Study design: Observational. Population: Schizophrenia (n=109). Intervention: Clozapine vs. Haloperidol (5-10 mg/day), olanzapine (20 mg/day), and healthy controls. Primary outcome: Heart rate and heart rate variability (HRV).

August 1, 2001Open Access

Association of autonomic dysfunction and clozapine

Key Result

Clozapine treatment in patients with schizophrenia was associated with significantly higher heart rate and lower heart rate variability compared to haloperidol, olanzapine, and healthy controls.

Study Design

Type

Observational (n=109)

Multicenter

Structured PICO

Does clozapine alter heart rate variability and cardiac repolarization compared to other neuroleptics and healthy controls in patients with schizophrenia?

Population

109 subjects total: 56 patients with schizophrenia on standard doses of neuroleptic monotherapy and 53 healthy subjects.

Intervention

Clozapine monotherapy (n=21)

Comparator

Haloperidol (n=18), olanzapine (n=17), and healthy matched control subjects (n=53)

Outcome

Heart rate variability (power spectral analysis), heart rate, and QTc intervalssurrogate

Clozapine is associated with significant autonomic dysregulation and cardiac repolarization changes (prolonged QTc) compared to other antipsychotics, highlighting its potential arrhythmogenic risk.

Abstract

BACKGROUND: Antipsychotic medications cause a wide range of adverse effects and have been associated with sudden death in psychiatric patients. AIMS: To supply power spectral analysis of heart rate variability as a tool to examine the arrythmogenic effects of neuroleptics. METHOD: Heart rate analysis was carried out in patients with schizophrenia on standard doses of neuroleptic monotherapy -- 21 were on clozapine, 18 on haloperidol and 17 on olanzapine -- and in 53 healthy subjects. RESULTS: Patients with schizophrenia on clozapine had significantly higher heart rate, lower heart rate variability and lower high-frequency and higher low-frequency components compared with patients on haloperidol or olanzapine and matched control subjects. Prolonged QTc intervals were more common in patients than controls. CONCLUSIONS: Patients treated with neuroleptic medications, especially clozapine, showed autonomic dysregulation and cardiac repolarisation changes. Physicians should be aware of this adverse reaction.

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