The mechanism of action of iloperidone, a psychotropic agent, is unknown, but researchers have proposed that the agent's efficacy is mediated through antagonism of dopamine type 2 (D₂) and serotonin type 2 (5-HT₂). This agent was approved on May 6, 2009, for the acute treatment of adult patients with schizophrenia.

Efficacy. The efficacy of iloperidone was evaluated in 2 placebo- and active-controlled, short-term trials. Both studies used the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) to assess the effects of drug treatment. The first study was a 6-week trial that evaluated iloperidone 12 to 16 mg/d and iloperidone 20 to 24 mg/d versus placebo and an active control. Iloperidone was initiated at a dose of 1 mg twice/d on Day 1, and the dose was increased as needed to 2, 4, 6, 8, 10, and 12 mg twice/d on Days 2, 3, 4, 5, 6, and 7, respectively. At 6 weeks, both dose ranges of iloperidone were superior to placebo on the end point of BPRS total score, whereas the active control was superior to iloperidone during the first 2 weeks of the trial. The second trial was a 4-week study that evaluated iloperidone 24 mg/d versus placebo and an active control. The titration schedule for iloperidone was similar to the schedule used in the first study. At 4 weeks, iloperidone was superior to placebo on the end point of PANSS total score; the efficacy of iloperidone was similar to that of the active control drug.

Safety. Elderly patients with dementia-related psychosis are at an increased risk of death when treated with atypical antipsychotic drugs; iloperidone is not approved for the treatment of dementia-related psychosis. Iloperidone has been associated with QTc prolongation. Neuroleptic malignant syndrome has been reported in patients treated with antipsychotic drugs. Tardive dyskinesia may develop in patients treated with antipsychotics. Atypical antipsychotics have been associated with hyperglycemia, some cases of which have been associated with ketoacidosis or hyperosmolar coma or death. In clinical trials, iloperidone-treated patients had increased weight gain compared with placebo-treated patients. Iloperidone should be used with caution in patients with a history of seizures or with a condition that may lower the seizure threshold. Iloperidone may induce orthostatic hypotension. Patients treated with antipsychotic agents have experienced leukopenia/neutropenia or agranulocytosis. Antipsychotic drugs have been associated with esophageal dysmotility and aspiration. Patients at high risk for suicide should be monitored during drug therapy. Iloperidone has the potential to impair cognitive and motor skills. The most common adverse events associated with iloperidone include dizziness, somnolence, dry mouth, nausea, and tachycardia.

Dosing. Iloperidone should be titrated from a low starting dose (1 mg twice/d) to avoid orthostatic hypotension. Daily dose adjustments to 2, 4, 6, 8, 10, and 12 mg twice/d can be made on Days 2, 3, 4, 5, 6, and 7, respectively. The target dose range is 6 to 12 mg twice/d; the maximum recommended dose is 12 mg twice/d.