Changes in weight, plasma lipids, and glucose in adults treated with ziprasidone: a comprehensive analysis of pfizer-initiated clinical trials.
BACKGROUND
Elevated cardiometabolic morbidity and mortality in patients with schizophrenia and bipolar disorder have been attributed to multiple sources, including antipsychotic treatment, which may adversely affect cardiometabolic risk factors. We therefore present here a comprehensive set of analyses of changes in metabolic parameters from ziprasidone clinical trials.


METHODS
The comprehensive set of analyses of metabolic changes conducted here was considered post hoc and exploratory. Changes in weight, fasting lipids, and fasting glucose from baseline to study end (last observation carried forward [LOCF]) for adult subjects in Pfizer-sponsored oral monotherapy randomized placebo-controlled ziprasidone clinical trials were analyzed by using an analysis of covariance model. In addition, available weight, fasting lipids, and fasting glucose data from all ziprasidone-treated subjects from all controlled and uncontrolled oral monotherapy studies of ziprasidone (102 studies; N = 12,599) conducted from 1992 to 2009 were analyzed similarly.


RESULTS
In short-term randomized controlled trials (RCTs) (duration ≤ 12 weeks), least squares mean ± SD change from baseline to end of study (LOCF) in weight was 0.64 ± 0.12 kg in ziprasidone-treated subjects (n = 1,386) versus -0.02 ± 0.14 kg in placebo-treated subjects (n = 747) (P < .0001); in long-term RCTs (duration > 12 weeks), the corresponding values were -0.96 ± 0.68 kg for ziprasidone (n = 363) and -1.68 ± 0.80 kg for placebo (n = 142) (P = .24). Mean ± SD weight change in ziprasidone-treated subjects from all controlled and uncontrolled studies ranged from 0.2 ± 5.6 kg at 6 weeks (n = 3,156) to 1.7 ± 10.1 kg at 36 months (n = 178). There were no significant differences between the ziprasidone and placebo groups in fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or glucose in the controlled studies, and there were minimal changes in ziprasidone-treated subjects in all controlled and uncontrolled studies.


CONCLUSIONS
This comprehensive analysis of data from the ziprasidone clinical trial database demonstrates limited evidence of any clinically significant adverse effects of ziprasidone on weight and consistent evidence of a neutral effect on fasting plasma lipids and glucose.
Pfizer Inc, New York, NY, USA. Elizabeth.Pappadopulos@pfizer.com
Elizabeth
E
Pappadopulos
John W
JW
Newcomer
Sheela
S
Kolluri
D014150:Antipsychotic Agents / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy; D001786:Blood Glucose / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D004345:Drug Industry / Q000706:statistics & numerical data; D005215:Fasting / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000097:blood*; D010879:Piperazines / Q000009:adverse effects*; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D013844:Thiazoles / Q000009:adverse effects*; D013997:Time Factors
D014150:Antipsychotic Agents; D001786:Blood Glucose; D008055:Lipids; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone