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Long-term safety and tolerability of iloperidone: results from a 25-week, open-label extension trial

  • Andrew J. Cutler (a1) (a2), Amir H. Kalali (a3) (a4), Greg W. Mattingly (a5) (a6), Jelena Kunovac (a7) (a8) and Xiangyi Meng (a9)...



Long-term use of the atypical antipsychotic iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension of a 4-week placebo- and ziprasidone-controlled clinical trial of iloperidone.


Patients received a dose of 24 mg/d (given as 12 mg twice daily; mean dose = 21.6 mg) that could be reduced to 12 mg/d (given once daily at bedtime) any time after day 35 at the investigator's discretion.


A total of 72/173 patients (41.6%) completed the open-label extension. Treatment-emergent adverse events (TEAEs), most mild to moderate in severity, included headache (13.9%), weight increase (9.2%), dizziness (6.9%), nausea (6.4%), sedation (6.4%), and insomnia (5.2%). The only notable dose-related TEAEs were increased weight and headache. Levels of serum glucose, lipids, and prolactin were essentially unchanged or decreased during treatment. In general, akathisia and extrapyramidal symptoms (EPS) improved or were unchanged during treatment. There was no signal of worsening of efficacy based on changes from baseline in the Positive and Negative Syndrome Scale-Total.


This study further supports the long-term safety and tolerability of iloperidone for the treatment of schizophrenia, including iloperidone's favorable effect on metabolic laboratory parameters and low propensity to cause akathisia or EPS.


Corresponding author

*Address for correspondence: Andrew J. Cutler, MD, Courtesy Assistant Professor, Department of Psychiatry, University of Florida, 8043 Cooper Creek Blvd., Suite 107, Bradenton, FL 34201, USA. (Email


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This clinical study was funded by Vanda Pharmaceuticals. Assistance with manuscript preparation was provided by Oxford PharmaGenesis, Inc., and this assistance was funded by Novartis Pharmaceuticals Corporation. The authors would also like to acknowledge project management support to Novartis provided by Arlene Kaufman of Research Pharmaceuticals, Inc. The authors wish to acknowledge the significant contributions of Dr. Paolo Baroldi and Rebecca Lannan, formerly of Vanda Pharmaceuticals, and of Dr. Curt Wolfgang and Jennifer Hamilton of Vanda Pharmaceuticals.



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