Objective:

To review the pharmacology, efficacy, and tolerability of iloperidone, a second-generation antipsychotic, in the treatment of acute schizophrenia in adults.

Data Sources:

English-language articles were obtained via MEDLINE (1966-March 2010) and International Pharmaceutical Abstracts (1970-March 2010) searches using the key words iloperidone, acute schizophrenia, atypical antipsychotics, second-generation antipsychotics, HP 873, P88–8991, P95–12113, and Fanapt. Bibliographies of selected articles were used to identify additional sources.

Study Selection and Data Extraction:

Available published articles reporting the results of human studies of iloperidone were reviewed for inclusion in this article. Additional information regarding pharmacology, adverse events, contraindications, and precautions was obtained from the manufacturer's prescribing information.

Data Synthesis:

Iloperidone is a second-generation antipsychotic approved for the treatment of acute schizophrenia in adults. Iloperidone is well absorbed upon oral administration, highly protein bound, and metabolized primarily by CYP3A4 and 2D6. Phase 3 clinical trials evaluating the efficacy of iloperidone demonstrated significantly higher response rates with iloperidone compared with placebo in the treatment of positive, negative, and cognitive symptoms associated with acute schizophrenia when the drug was given in doses up to 24 mg daily. Dizziness, dry mouth, and nausea were the most commonly reported adverse events and appear to be dose related. Additional adverse events occurring in 5% or more of patients include orthostatic hypotension, somnolence, tachycardia, fatigue, nasal congestion, and weight increase. Iloperidone should be titrated slowly over a 7-day interval to avoid the potential for orthostatic hypotension. Product labeling includes a black box warning against the use of iloperidone in dementia-related psychosis and precautions regarding QT interval prolongation.

Conclusions:

Iloperidone is an effective treatment for the symptoms of acute schizophrenia in adults. Additional studies are needed to assess comparative effectiveness with other pharmacologic treatments of schizophrenia, long-term efficacy, and long-term safety.