Background: Despite numerous studies of diabetes mellitus type II (DM-II) in schizophrenia and schizoafective dis- order, there have been no studies on the glycemic efects of switching patients with long-standing symptomatic DM-II from their current antipsychotic regimen to ziprasidone. Methods: An open-label, prospective inpatient study was conducted with 26 suboptimally responding inpatients with DSM-IV diagnoses of schizophrenia or schizoafective disorder and comorbid DM-II who were switched to ziprasidone monotherapy and followed for 8 weeks. Outcome measures were fasting glucose, triglycerides, cholesterol, insulin levels, capillary blood glucose levels and weight. Afer a 3-week cross-titration period, patients were treated with ziprasidone up to a dose of 320 mg daily. Results: Of the 26 study participants, 16 completed the entire study period of 63 days and 10 (38.46%) discontinued participation, pri- marily due to psychotic relapse. Tere was a statistically signifcant reduction in fasting glucose (F=4.43, p=0.05; 14.68 mg/dL mean reduction), capillary blood glucose levels (F=8.90, p=0.01; 25.36 mg/dL mean reduction), weight (F=4.46, p=0.05; 4.68 lb mean weight loss) and Body Mass Index (F=4.40, p=0.05; 3.62 kg/m 2 mean reduction). Tere was also a reduction in the use of antidiabetic medications afer the switch to ziprasidone. Nine (34.62%) patients met criteria for metabolic syndrome (MetS) at baseline, as compared to 4 (15.38%) at endpoint. No change was observed in positive symptoms (F=0.62, p=0.44), negative symptoms (F=1.47, p=0.24) and in total PANSS score (F=0.12, p=0.74). Conclu- sions: Tis study suggests signifcant improvement in metabolic side efects and MetS in the subset of the patients who were able to tolerate switching from a polypharmacy regimen to ziprasidone. Tere was a large discontinuation rate, which limited the sustained benefcial efects of ziprasidone. Te decision to switch to ziprasidone in patients with prior suboptimal response has to balance the potential metabolic benefts and the potential relapse risks of the individual patient frst and foremost. Original Contributions Ziprasidone’s Efect on Metabolic Markers in Patients with Diabetes and Chronic Schizophrenia 1 Department of Psychiatry, New York University School of Medicine, New York, NY 2 Manhattan Psychiatric Center, New York, NY 3 Psychopharmacology Research Unit, Nathan Kline Institute for Psychiatric Research, New York, NY 4 ProPhase LLC., New York, NY 5 Visiting Scientist, Nathan S. Kline Institute for Psychiatric Research Address for correspondence: Jean-Pierre Lindenmayer, MD, Clinical Director, Manhattan Psychiatric Center, Wards Island, NY 10035 Phone: 646-672-6004; E-mail: lindenmayer@nki.rfmh.org Submitted: May 5, 2010; Revised: September 16, 2010; Accepted: November 17, 2010 J.P. Lindenmayer 1, 2, 3 , Frank Tedeschi 1 , Anna Yusim 1 , Anzalee Khan 2, 4 , Saurabh Kaushik 2, 3 , Robert C. Smith 1, 5 , Mohan Parakadavil 2, 3 Key Words: Ziprasidone, Diabetes, Switch, Schizophrenia, Schizoafective Disorder, Metabolic Syndrome Abstract Background Te association between schizophrenia and increased risk of diabetes mellitus type II (DM-II) has long been rec- ognized, even before the introduction of second-generation antipsychotics (SGAs) (1-4). In addition to an increased risk of DM-II, schizophrenia is also associated with increased prevalence of metabolic syndrome (MetS) (5, 6), with es- timates ranging from 25.1 to 66.7% of females and 19.4 to 47.3% of males (7-10). Elevated rates of DM-II and MetS have also been reported in our own population of inpatients with chronic schizophrenia (7): 43.7% had a Body Mass Index (BMI) ≥30 (indicating obesity) and 26.2% presented with DM-II, impaired fasting glucose, and/or impaired glu- cose tolerance, while 25.5% met World Health Organization (WHO) criteria for MetS. Among factors implicated in the Clinical Schizophrenia & Related Psychoses January 2012 • 185