NEW YORK (Reuters Health) – In patients with schizophrenia, clozapine does not seem to increase the risk of cardiovascular death relative to risperidone, despite known differences in cardiometabolic risk profiles for these two antipsychotic drugs, a retrospective study suggests.

Many factors might put schizophrenic individuals at risk for premature mortality, “and the extent to which antipsychotics contribute to this risk remains unknown,” lead author Dr. Deanna L. Kelly of the Maryland Psychiatric Research Center in Baltimore noted in an email to Reuters Health.

In an online report in the January Journal of Clinical Psychiatry, she and her colleagues point out that while the superiority of clozapine over risperidone for refractory schizophrenia is “well established,” clozapine causes significant weight gain and may increase the risk of diabetes and other metabolic abnormalities.

In their paper, the researchers compare cardiovascular disease (CVD)-related mortality in a cohort treated with clozapine (n = 1084) and a matched group never exposed to clozapine and treated with risperidone instead (n = 602).

Over a 6- to 10-year follow-up period (1994-2004), 136 subjects died, including 43 who died of CVD.

“We did not find a significant difference in mortality risk, especially in the population started on medication before the age of 55 years,” Dr. Kelly wrote to Reuters Health. At 5 years, mortality due to CVD in patients younger than 55 years when starting medication was 1.1% in the clozapine group and 1.0% in the risperidone group; at 10 years, it was 2.7% and 2.8%, respectively.

“We did see some increase in mortality with clozapine in patients treated with clozapine over the age of 55 years, but this age group was small and larger samples for longer study periods may be required,” Dr. Kelly said.

Specifically, in patients who started medication at age 55 or older, CVD mortality was 8.5% with clozapine and 3.6% with risperidone at 5 years and 16.0% and 5.7%, respectively, at 10 years (p=0.144).

In Dr. Kelly’s view, clozapine “remains a viable option” for treatment-resistant patients with schizophrenia, particularly those younger than 55, and it “may be underutilized due to many factors including its weight gain liability.”

The current findings also confirm that patients with schizophrenia have a significantly higher risk for CVD-related mortality compared to the general population, Dr. Kelly points out.

In Maryland, where she works, the risk of cardiovascular-related mortality in people with schizophrenia is about 4.0 times higher than in the general population, and the difference is particularly marked in female patients, who have 6.2 times the risk of the general public, Dr. Kelly told Reuters Health.

“We remain convinced that greater attention should be paid to healthier lifestyles such as increasing exercise, improving food choices and smoking cessation in people with schizophrenia,” she said.

In terms of drug choice, “weighing the risk/benefit profile for each medication still remains essential and data from this study adds to the literature on the risk profile of clozapine in chronic schizophrenia,” Dr. Kelly noted.

Reference:
J Clin Psychiatry 2010.