Efficacy of Iloperidone in the Treatment of Schizophrenia

Abstract

Iloperidone is an atypical antipsychotic in development for the treatment of schizophrenia. This report examines efficacy results from three 6-week, randomized, double-blind, placebo- and active comparator-controlled studies in patients with schizophrenia or schizoaffective disorder. Multiple doses of iloperidone were studied. Active comparators (haloperidol 15 mg/d, or risperidone 4-8 mg/d) were included to confirm trial validity. The primary protocol-defined efficacy variable in Study 1 was change from baseline to end point in Positive and Negative Syndrome Scale total scores; in Studies 2 and 3, it was change in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale scores. Results were assessed through analysis of covariance using last observation carried forward in the intent-to-treat population. In total, 1943 patients were randomized. At least 1 iloperidone dosing group in each study demonstrated significantly better efficacy than placebo (Study 1, iloperidone 12 mg/d [P = 0.047]; Study 2, 4-8 mg/d [P = 0.012] and 10-16 mg/d [P = 0.001]; and Study 3, 20-24 mg/d [P = 0.010]). Active controls were also significantly more effective than placebo in each trial, thus validating the trials. Additional analysis in patients who received active treatment for at least 2 weeks indicated comparable efficacy score reductions at 6 weeks for patients receiving iloperidone 20 to 24 mg/d versus those receiving haloperidol or risperidone. Risk for motor-related adverse events (eg, akathisia and extrapyramidal symptoms) was lower with iloperidone than with risperidone and haloperidol and was generally similar to placebo. These trials indicate that iloperidone is effective for the treatment of schizophrenia.

Long-term Effectiveness and Tolerability Profile of Iloperidone in Patients of Psychosis

“…Both short-and long-term adverse effects noted were in line with other workers. 16,17,21,23 Adverse effects did not cause any discontinuation of therapy in our study. Other authors observed that iloperidone discontinuation due to adverse events was similar to placebo (i.e., 4.8%).…”

“…Other authors observed that iloperidone discontinuation due to adverse events was similar to placebo (i.e., 4.8%). 16,23 Further, neither extrapyramidal signs and akathisia, nor hypersensitivity to iloperidone was observed. This was in contrast to CATIE study, which reported 4 to 8% extrapyramidal symptoms even with newer agents.…”

“…Other short-and long-term clinical trials also observed similar findings including those of ours. 16,17,[19][20][21] 24 conducted a metaanalysis and data were analyzed from 3,210 patients who received iloperidone for up to 2 years. Three-dose ranges of iloperidone 4 to 8, 10 to 16, and 20 to 24 mg/day were used.…”

Changes in weight and metabolic parameters following long-term iloperidone use: A meta-analysis of data from 9 Phase II and III trials of iloperidone

“…The full integrated safety database includes all adult patients enrolled in 9 clinical studies who received at least 1 dose of study drug--3210 patients were exposed to iloperidone during any phase of the studies (Tables 1 and 2) and the detailed methods and enrollment criteria for each study have been previously published in a series of articles [10][11][12][13]. A total of 1344 patients were exposed to iloperidone during the double-blind phase of 4 randomized, placebo-controlled studies (Studies 3000, 3004, 3005, and 3101); 281 patients were exposed to iloperidone during a long-term, active-control phase and/or an open-label extension phase of these studies; and 1585 patients were exposed to iloperidone during 5 active-controlled studies (Studies 2001, 2328, 3001, 3002, and 3003).…”

Nasal congestion with iloperidone therapy in a case series

“…3 A pooled analysis of safety data by Weiden et al from those 3 trials demonstrated the common reported adverse effects of iloperidone as dizzinness, dry mouth, somnolence and dyspepsia. Extra pyramidal symptoms were rather improved with iloperidone.…”