Iloperidone for the treatment of schizophrenia

Abstract

Iloperidone is a recently approved antipsychotic agent indicated for the acute treatment of schizophrenia in adults. Iloperidone is characterized as a serotonin 5-HT(2A) and dopamine D(2) receptor antagonist, which makes its core mechanism of action similar to other second-generation antipsychotic agents. The affinity (or lack thereof) of iloperidone for other receptors (e.g., histamine, muscarinic, α(1)-adrenoceptors, serotonin) results in a unique side effect and perhaps response profile that may make it an additional option for patients who have previously not tolerated or adequately responded to other available agents. Iloperidone has been studied in over 3,200 patients throughout its development. Its efficacy appears to be similar to haloperidol, risperidone and ziprasidone. It appears to be safe with minimal extrapyramidal side effects, weight gain and prolactin elevation. A cautious dosing and titration schedule is recommended at the initiation of therapy due to the potential for orthostatic hypotension and dizziness. Drug interactions through the CYP3A4 and CYP2D6 enzymes, along with the potential for QT prolongation, may influence its use in certain patients. Genetic studies conducted during drug development may facilitate the clinical use of pharmacogenomic tests to aid clinicians in optimizing the risk-benefit ratio of iloperidone. The purpose of this review is to summarize the chemistry, pharmacology and clinical aspects of iloperidone, with the goals of identifying key scientific and clinical issues for its use, as well as assessing the potential utility of iloperidone for the treatment of schizophrenia.

The Challenge of Adherence in Schizophrenia

“…Results of efficacy studies are difficult to generalize to routine clinical practice and direct comparison of the different agents has produced inconsistent differences in efficacy in the acute setting, with any differences generally small in magnitude, inadequately tested and/or possibly influenced by pharmaceutical industry input into the design and reporting of the clinical trials, low and fixed doses, biased samples (selected patients) and differing inclusion/ exclusion criteria, statistics and methodologies [28][29][30]. Results of efficacy studies are difficult to generalize to routine clinical practice and direct comparison of the different agents has produced inconsistent differences in efficacy in the acute setting, with any differences generally small in magnitude, inadequately tested and/or possibly influenced by pharmaceutical industry input into the design and reporting of the clinical trials, low and fixed doses, biased samples (selected patients) and differing inclusion/ exclusion criteria, statistics and methodologies [28][29][30].…”

“…Iloperidone causes minimal extrapyramidal symptoms, prolactin elevation and weight gain [30]. However, prolongation of the QTc interval is similar to haloperidol and ziprasidone, which is of concern (the latter did not receive a UK license because of potential cardiotoxicity) [27].…”

“…However, prolongation of the QTc interval is similar to haloperidol and ziprasidone, which is of concern (the latter did not receive a UK license because of potential cardiotoxicity) [27]. In addition, drug interactions via the CYP3A4 and CYP2D6 enzymes may restrict the use of iloperidone [30].…”