Switching to Lurasidone following 12 months of treatment with Risperidone: results of a 6-month, open-label study

Abstract

Background: Patients with a diagnosis of schizophrenia are at an increased risk for developing metabolic syndrome, which is associated with greater cardiovascular morbidity and mortality. Treatment with some commonly used antipsychotic medications may increase the risk of developing metabolic syndrome. The aim of the study was to evaluate the safety of lurasidone in patients who continued lurasidone or switched from risperidone to lurasidone. A secondary aim was assessment of the effect of long-term lurasidone on the Positive and Negative Syndrome Scale (PANSS).

Methods: The treatment sample in the current study consisted of clinically stable patients with schizophrenia (N = 223) who had completed a 12-month, double-blind study of lurasidone vs. risperidone. In the current extension study, all patients received 6 months of open-label treatment with lurasidone, either continuing lurasidone assigned during the preceding double-blind trial, or switching from double-blind risperidone to lurasidone. Safety and tolerability parameters included body weight, prolactin, and metabolic laboratory tests.

Results: Six months of OL treatment with lurasidone was generally well-tolerated, with a low incidence of parkinsonism (4.5%) and akathisia (3.1%). Overall, few adverse events were rated as severe (4.9%), and discontinuation due to an adverse event was low in the lurasidone continuation vs. risperidone switch groups (3.7% vs. 6.9%). In the lurasidone continuation versus risperidone switch groups, change from OL baseline to 6-month endpoint (observed case) was observed in mean body weight (- 0.6 vs. -2.6 kg), median total cholesterol (- 4.0 vs. + 4.5 mg/dL), triglycerides (- 4.5 vs. -5.5 mg/dL), glucose (0.0 vs. -3.0 mg/dL) and prolactin (males, + 0.15 vs. -11.2 ng/mL; females, + 1.3 vs. -30.8 ng/mL). Improvement in PANSS total score was maintained, from OL baseline to endpoint in the continuation vs. switch groups (+ 1.0 vs. -1.0; OC).

Conclusions: In this 6-month extension study, lurasidone treatment was generally well-tolerated and associated with minimal effects on weight, metabolic parameters, and prolactin levels. Patients who switched from risperidone to lurasidone experienced reductions in weight, metabolic parameters and prolactin levels commensurate with increases in these safety parameters experienced during the previous 12 months of treatment with risperidone.

Trial registration: ClinicalTrials.gov NCT00641745 (Date of Registration: March 24, 2008).

Keywords: Adverse effects; Antipsychotic agents; Lipids; Lurasidone; Metabolic; Prolactin; Schizophrenia; Weight.

Conflict of interest statement

GWW reports receiving research support from AstraZeneca, Ayerst, Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly and Co., Forest Laboratories, Inc., GlaxoSmithKline, Janssen Pharmaceuticals, Inc., Lundbeck, McNeil, Merck & Co., Inc., Novartis, Organon, Otsuka America Pharmaceutical, Inc., Pfizer Inc., Sanofi-Synthelabo, Schwabe/Ingenix, Shionogi Inc., Shire plc, Solvay Pharmaceuticals, Sunovion Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc., and Vanda Pharmaceuticals Inc.; serving on the speakers’ bureaus for Forest, Novartis, Noven Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc., Shire plc, and Sunovion Pharmaceuticals Inc.; and serving as a consultant for Eli Lilly and Co., Forest, Novartis, Noven Pharmaceuticals, Inc., Shire plc, Shionogi Inc., and Sunovion Pharmaceuticals Inc.

PMH has received honoraria for lecturing and consultancy work from Allergan, Galen, Janssen, Lundbeck, NewBridge Pharmaceuticals, Otsuka, Sunovion and Teva; and conference support from Janssen, Lundbeck, NewBridge Pharmaceuticals and Sunovion Pharmaceuticals Inc.

MT, JX, DP, AP, and AL are employees of Sunovion Pharmaceuticals Inc. AL is an associate editor on the BMC Psychiatry editorial board.

Figures

Fig. 1

Patient Disposition. LUR = lurasidone; RIS = risperidone; DB: double-blind; OLE: open-label extension

Fig. 2

Median Change in Weight From Double-Blind Baseline Through 6 Months of Open-Label Treatment With Lurasidone, by Treatment Assignment in the Double-Blind Study. LUR = lurasidone; RIS = risperidone. *Subgroup entering open-label extension; 6-month completer analysis: LUR-LUR, n = 109; RIS-LUR, n = 66. †Patients in the RIS-LUR group received risperidone in the 12-month, double-blind study

Fig. 3

Median Change in Prolactin From Double-Blind Baseline Through 6 Months of Open-Label Treatment With Lurasidone, by Treatment Assignment in the Double-Blind Study. 3-A. Males. LUR = lurasidone; RIS = risperidone. *Subgroup entering open-label extension; 6-month completer analysis: LUR-LUR, n = 102; RIS-LUR, n = 68. †Patients in the RIS-LUR group received risperidone in the 12-month, double-blind study. 3-B. Females. LUR = lurasidone; RIS = risperidone. *Subgroup entering open-label extension; 6-month completer analysis: LUR-LUR, n = 34; RIS-LUR, n = 29. †Patients in the RIS-LUR group received risperidone in the 12-month, double-blind study

Fig. 4

Mean PANSS Total Score From Double-Blind Baseline Through 6 Months of Open-Label Treatment With Lurasidone, by Treatment Assignment in the Double-Blind Study. LUR = lurasidone; PANSS = Positive and Negative Syndrome Scale; RIS = risperidone. *Subgroup entering open-label extension; 6-month completer analysis: LUR-LUR, n = 115; RIS-LUR, n = 71. †Patients in the RIS-LUR group received risperidone in the 12-month, double-blind study