Long-Term Changes in Weight and Plasma Lipids during Maintenance Treatment with Ziprasidone

Abstract

To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N ¼ 185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n ¼ 43), olanzapine (n ¼ 71), or conventional antipsychotic agents (n ¼ 71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global ImpressionFSeverity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (po0.001) and 6.9 kg (po0.005) for patients previously treated with olanzapine and risperidone, respectively. These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids.

Effectiveness of Lurasidone for Patients With Schizophrenia Following 6 Weeks of Acute Treatment With Lurasidone, Olanzapine, or Placebo

“…The magnitude of the reduction in weight and lipid parameters found after switching from olanzapine to lurasidone in this extension study appeared clinically relevant and suggests that lurasidone may be a useful treatment for patients with antipsychoticinduced weight gain or dyslipidemia. These improvements in metabolic parameters were consistent with those reported in other studies that have examined the effects of switching from atypical antipsychotic medications with higher metabolic liability to those with lower metabolic liability, [23][24][25][26][27][28] as well as a recent metaanalysis of short and longerterm placebocontrolled and headto head trials of several atypical antipsychotics in patients with schizophrenia and bipolar disorder, which reported that lurasidone had the lowest potential for weight gain among the atypical antipsychotics studied. 29 Improvements in psychopathology and reductions in weight and dyslipidemia were also observed in a recently completed formal switch study in which stable outpatients with schizophrenia were switched to lurasidone from other antipsychotic agents.…”

Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: Prospective data from phase 1

“…As expected from earlier studies (Weiden et al, 2007), ziprasidone did not significantly worsen and often improved metabolic indices, particularly central adiposity and triglycerides.…”

Effectiveness of Lurasidone in Patients with Schizophrenia or Schizoaffective Disorder Switched From Other Antipsychotics

“…1 Lurasidone may thus be a logical antipsychotic to switch to in the presence of antipsychotic-associated weight gain. Switching to an agent with lower metabolic liability, a strategy suggested in the Patient Outcomes Research Team (PORT) recommendations, 29 has previously been supported by switch studies with agents such as ziprasidone 11 and aripiprazole, 10,30 as well as by the Phase 2T report from the CATIE trials. 31 As noted in reports of switching studies with other agents, a concern has been that switching patients from one antipsychotic to another can lead to tolerability problems, transient symptom exacerbations, or increased use of acute-care services.…”

“…9 Switching for the purpose of assessment of improvement in metabolic variables was the specific focus of a recently reported study of aripiprazole, 10 with benefits and risks observed similar to those shown in switch studies involving ziprasidone. 11 To better understand the effects of switching antipsychotic medication regimens to lurasidone among outpatients under "real-world" conditions, we undertook this study to evaluate…”