Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis

J Clin Psychopharmacol. 2017 Dec;37(6):708-712. doi: 10.1097/JCP.0000000000000792.

Abstract

Background: Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment.

Methods: Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion.

Results: Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment.

Conclusions: This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects*
  • Cardiotoxicity
  • Clozapine / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Schizophrenia / drug therapy*
  • Ventricular Dysfunction, Left / chemically induced*
  • Ventricular Dysfunction, Left / diagnosis*

Substances

  • Antipsychotic Agents
  • Clozapine