The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1 year, open-label, prospective study

Abstract

Objective:

Metabolic syndrome (MetS) is prevalent in subjects with schizophrenia-related psychotic disorders and contributes to increased rates of premature death due to cardiovascular disease. This study examined the impact of switching from another antipsychotic to ziprasidone on the distribution of the number of risk factors for MetS in subjects with schizophrenia or related psychotic disorders.

Research design and methods:

In this 1 year, open-label, prospective study, all subjects received ziprasidone 40–160 mg/day. Standard exclusion criteria included treatment resistance, physical health disorders, and substance abuse. The primary end point was the percentage of subjects achieving a reduction from baseline of at least one risk factor for MetS at end point (week 52 or premature discontinuation) in the per-protocol population (treated for at least 16 weeks). Secondary end points included the mean change from baseline in number of MetS risk factors, the prevalence of MetS, individual MetS risk factors (waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and glucose), and 10 year coronary heart disease (Framingham score) risk.

Clinical trial registration:

www.clinicaltrials.gov: NCT00748566.

Main outcome measures:

Of 114 evaluable subjects, 58.77% demonstrated one less MetS risk factor at week 52 (last observation carried forward) compared with baseline. Secondary end points also improved, with reductions in other metabolic parameters (fasting low-density lipoprotein cholesterol, total cholesterol and serum insulin, weight, body mass index and glycosylated hemoglobin [HbA_1c]). The 10 year coronary heart disease risk decreased continually over time. The open-label and uncontrolled design is a limitation of the study.

Conclusions:

Ziprasidone treatment reduced both the rate of MetS and its individual risk factors in subjects with schizophrenia and related psychotic disorders. The results have implications for the selection of first-line treatments in schizophrenia and related psychotic disorders, and provide treatment options for subjects who have developed MetS as a result of other antipsychotics.

Keywords::

• Atypical antipsychotic
• Metabolic syndrome
• Schizophrenia
• Ziprasidone

Transparency

Declaration of funding

This study was sponsored by Pfizer Canada Inc.

Declaration of financial/other relationships

P.C. has disclosed that he has served on advisory boards, speaker bureaus, or as a consultant and has received honoraria, research grants, travel grants, and educational grants from Pfizer, AstraZeneca, Novartis, Janssen, Eli Lilly, Bristol-Myers Squibb, Lundbeck, GlaxoSmithKline, Sunovion, Mylan, Valeant, and Otsuka. F.S.M. and F.T. have disclosed that they are contracted employees of Pfizer.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

This study was sponsored by Pfizer Canada Inc. Editorial support was provided by Hajira Koeller, PhD, of PAREXEL, and funded by Pfizer Canada Inc.

The A1281173 study group included the following physician investigators: Heather Milliken, Roumen Milev, Sunny Johnson, Saibal Nandy, Richard Williams, Beverly Adams, Leonardo Cortese, Kevin Kok, Alexander McIntyre, Kevin Hogan, Brian Ticoll, Paul Roy, Linda Beauclair, Gilbert Dru, Joseph Polimeni, Norman Costigan, Mark Rabinovitch, Ofer Agid, M.S. Renuka-Prasad, Autar K. Munshi, Rajendra Harricharan, Smadar Valerie Tourjman, Peter G. Turner, Ramamohan Veluri, Ivan Kowalchuk, Alla Kirshner, and Ranjith Chandrasena.

Previous presentations: Interim results were presented as posters at the 60th Annual Meeting of the Canadian Psychiatric Association, 23–26 September 2010, Toronto, Ontario, Canada; and at the 166th Annual Meeting of the American Psychiatric Association, 18–22 May 2013, San Francisco, USA.