Iloperidone: an old tune variation or the first implementation of personalized medicine into psychiatry?
Abstract
In 2009, following lengthy registration process, the US FDA approved new antipsychotic iloperidone. Iloperidone has a high affinity to serotonin 5-HT2a and dopamine D2 receptors.
It is an antagonist of 5-HT2c and 5-HT6 and partial agonist of 5-HT1a, with high affinity to dopamine D3 and moderate to D4 receptors, high affinity to α1 and moderate to α2c adrenoreceptors, low to histamine H1 and minimal to muscarine receptors. Antipsychotic efficacy was shown in acute placebo-controlled trials of schizophrenia.
Long-term relapse prevention studies demonstrated efficacy comparable to that of haloperidol. The recommended effective daily dose is 12-24 mg.
The most frequently reported side effects were transitory orthostatic hypotension, especially during the first week of treatment, QTc interval prolongation, dizziness, headache, dry mouth, and insomnia, all dose-dependent. Comparing to haloperidol and risperidone, iloperidone was associated with a low risk of EPS and akathisia.
Weight gain in six weeks was similar to that observed in risperidone, it has minimal adverse impact on biochemical parameters. Iloperidone was tested for genetic biomarkers of efficacy and safety.
Whole-genome association studies identified six single nucleotide polymorphisms (SNP) associated with its antipsychotic effects and six SNP that defined genotypes with low and high risk of QT interval prolongation. This data has to be further replicated.
Iloperidone represents another SDA-like atypical antipsychotic; nevertheless, its pharmacogenetics may be an opportunity for individualized treatment, tailored administration to potential responders and minimization of side effects