Source: J Am Coll Cardiol  |  Posted 6 years ago

Zyprexa Associated With Significant Increases In Weight, Cholesterol And Insulin

NEW YORK, NY -- August 8, 2005 -- The antipsychotic Geodon[^]?[] (ziprasidone HCl) is as effective as Zyprexa? (olanzapine) in maintenance treatment of patients with schizophrenia, but has significantly less adverse effect on body weight, cholesterol, and insulin, according to results from a 6-month, double-blind, head-to-head study published in the current issue of the American Journal of Psychiatry.

These study results come amidst concern that some second-generation antipsychotics (SGAs) can cause weight gain and metabolic adverse events -- including raised cholesterol and insulin levels -- which can increase patients' risks for obesity, diabetes and cardiovascular disease.

"Geodon's equal long-term efficacy but lack of metabolic adverse effects are important advantages over Zyprexa," said lead author and investigator George Simpson, MD, professor of research psychiatry and interim chair, Keck School of Medicine of the University of Southern California. "Given that patients often take antipsychotic medications for many years, it's important for physicians to consider potential long-term risks, such as cardiovascular disease and diabetes, when selecting the best treatment."

Study and Findings

In this continuation study, 126 patients with schizophrenia or schizoaffective disorder given flexibly dosed Geodon or Zyprexa demonstrated comparable responses on standard measures of schizophrenia symptoms at 6 months (85.5% for ziprasidone and 84.5% for olanzapine), maintaining improvements seen in the core 6-week trial.

However, patients taking Zyprexa had significant increases versus baseline in average body weight (+11 lbs) compared with a mean weight loss of -1.8 pounds for patients on Geodon. Zyprexa patients also experienced significant increases from baseline in total cholesterol (+13.0 mg/dL), low-density lipoprotein cholesterol (+17.0 mg/dL) and fasting insulin (+2.0 mcU/mL); there were no significant changes seen with Geodon.

The frequency of treatment-related adverse events (mostly mild to moderate) was similar in the Geodon and Zyprexa groups (58.2% and 66.2%, respectively). The most common treatment-related adverse events were of the nervous system (50.9% for Zyprexa and 46.5% for Geodon) and digestive system (27.3% for Zyprexa and 22.5% for Geodon). More adverse events related to metabolic adverse effects and weight gain were seen in Zyprexa patients vs. Geodon patients (21.8% vs. 3.6%, respectively).

This study was a double-blinded extension of an initial, 6-week trial in 269 patients, which also showed equivalent efficacy for the two SGAs. Patients who responded to Geodon (n=55) and Zyprexa (n=71) in the initial study were enrolled in the 6-month extension. Primary efficacy measures included scores on the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression?Severity (CGI?S); other efficacy measures included scores on Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS).

Schizophrenia and Metabolic Disorders

Individuals with schizophrenia have a 20% shorter life expectancy than the population at large and a greater vulnerability to several illnesses, including diabetes, coronary heart disease, hypertension, and emphysema. These increased risks are partly due to lifestyle factors, including poor dietary habits, high rates of smoking, and the use of alcohol and street drugs.1 In addition, while SGAs represent a major

advance in the management of schizophrenia, some are associated with significant increases in body weight and blood levels of triglycerides, cholesterol and insulin ? all of which can increase the risk for diabetes and cardiovascular disease.2,3

However, according to a consensus statement by the American Diabetes Association, American Psychiatric Association and other health organizations, Geodon is associated with little or no significant risk of weight gain, diabetes, or dyslipidemia, although it has not been used as extensively as other agents.4 Additionally, studies show that patients who switched from some other SGAs to Geodon showed substantial weight loss, as well as improvements in cholesterol and triglycerides.5

About Geodon

Approved in the United States in February 2001 for the treatment of schizophrenia and in 2004 for acute bipolar mania, Geodon is licensed in 73 countries, and more than 5 million prescriptions have been written worldwide. It is widely accepted on hospital, Medicaid, national Veterans Administration (VA) and managed care formularies.

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Geodon is not approved for the treatment of elderly patients with dementia-related psychosis.

Geodon is contraindicated in patients with a known history of QT prolongation, recent acute myocardial infarction, or uncompensated heart failure, and should not be used with other QT-prolonging drugs.

Geodon has a greater capacity to prolong the QTc interval than several antipsychotics. In some drugs, QT prolongation has been associated with torsade de pointes, a potentially fatal arrhythmia. In many cases this would lead to the conclusion that other drugs should be tried first.

Hyperglycemia-related adverse events, sometimes serious, have been reported in patients treated with atypical antipsychotics. There have been few reports of hyperglycemia or diabetes in patients treated with Geodon, and it is not known if Geodon is associated with these events. Patients treated with an atypical antipsychotic should be monitored for symptoms of hyperglycemia.

Discovered and developed by Pfizer, Geodon is a serotonin and dopamine antagonist. In short-term schizophrenia trials, the most commonly observed adverse events associated with Geodon at an incidence of >/=5% and at least twice the rate of placebo were somnolence and respiratory tract infection.

REFERENCES:
1. Simpson GM, Weiden P, Pigott T, Murray S, Siu CO, Romano SJ. Ziprasidone vs. olanzapine in schizophrenia: a 6-month, blinded, multicenter continuation study. Am J Psychiatry, August 2005
2. Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161: 1334-1349.
3. Masand PS. Weight gain associated with psychotropic drugs. Expert Opinion on Pharmacotherapy 2000; 1(3): 377-389.
4. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004 Feb;27(2):596-601
5. Weiden P, Daniel D, et al. Improvement in indices of health status in outpatients with schizophrenia switched to ziprasidone. Journal of Clinical Psychopharmacology. 2003; 23(6):595-600.

SOURCE: Pfizer Inc.