Iloperidone for schizophrenia
New treatment option for patients who have not fully responded to or cannot tolerate other antipsychotics
Tolerability
Clinicians might consider iloperidone when seeking to switch a patient to an antipsychotic with a potentially lower side-effect burden.6,11 Compared with risperidone, iloperidone has a lower liability for extrapyramidal symptoms (EPS) and does not cause clinically significant prolactin elevation (Table 3).5,7-9 Compared with ziprasidone, iloperidone has a lower EPS and akathisia liability. Somewhat greater weight gain was seen with iloperidone when compared with ziprasidone in a 4-week study (iloperidone, +2.8 kg; ziprasidone, +1.1 kg; placebo, +0.5 kg) but the 2 drugs’ effects on triglycerides and cholesterol were comparable.9
Iloperidone has a similar degree of QTc prolongation as ziprasidone (mean 9 msec at the highest dosage of 12 mg bid). Safety studies including administration of maximal doses of iloperidone with CYP3A4 and CYP2D6 inhibitors showed a mean QTc prolongation of 19 msec without clinically significant problems, and iloperidone has not been associated with serious arrhythmia.4 Iloperidone should not be prescribed to patients with significant cardiac problems or electrolyte disturbances, however, or those taking drugs known to have clinically significant QTc/proarrhythmic properties, such as thioridazine, droperidol, pimozide, or methadone.4
Iloperidone has the same safety concerns associated with other atypical antipsychotics, including tardive dyskinesia and neuroleptic malignant syndrome. Like other atypical antipsychotics, iloperidone carries a warning of increased mortality risk in elderly patients with dementia-related psychosis.
Dose-related side effects include dizziness, orthostatic hypotension, and tachycardia. Dizziness occurred more often at higher doses (20% at 20 to 24 mg/d vs 10% at 10 to 16 mg/d vs 7% in placebo groups). Presumably these side effects are related to NEα1 antagonism and are the basis for the recommended dose-titration schedule described below. Clinical trials do not seem to demonstrate a dose-response relationship for acute EPS or akathisia.
Table 3
Common side effects: Iloperidone vs other antipsychotics*
| Other antipsychotic | Less likely or less severe with iloperidone | More likely or more severe with iloperidone |
|---|---|---|
| Haloperidol4,8 | EPS Akathisia Prolactin elevation | Weight gain Orthostasis |
| Olanzapine | Dyslipidemia Weight gain Sedation | Orthostasis |
| Quetiapine | Dyslipidemia Sedation | EPS |
| Risperidone4,6 | EPS Prolactin elevation Akathisia | None |
| Ziprasidone7 | EPS Akathisia | Weight gain Orthostasis |
| Aripiprazole | Akathisia | Weight gain Orthostasis |
| * Iloperidone has been compared head-to-head with haloperidol, risperidone, and ziprasidone in clinical trials. Other suggested antipsychotic side effect liabilities are based on indirect comparisons | ||
| EPS: extrapyramidal symptoms | ||
The approved dosage range for iloperidone is 12 to 24 mg/d, given as 6 to 12 mg bid. Some trials suggest a dose-response relationship, with 24 mg being more effective than lower target doses.5 Reduce the target dosage of iloperidone by one-half when administering it concomitantly with medications that are strong CYP2D6 or CYP3A4 inhibitors.
Titration schedule. Because iloperidone’s relatively strong NEα1 antagonism creates risk for initial orthostatic hypotension, the drug needs to be titrated to the target dose over 4 to 7 days:
- 1 mg bid at day 1
- 2 mg bid at day 2
- 4 mg bid at day 3
- 6 mg bid at day 4 (for a target dosage of 12 mg/d)
- 8 mg bid at day 5
- 10 mg bid at day 6
- 12 mg bid at day 7 (for a target dosage of 24 mg/d).
Monitor patients for dose adjustments based on clinical status, concomitant use of other medications (including antipsychotics), and tolerability of up-titration.
The need to titrate iloperidone slowly to reach efficacious acute antipsychotic doses may lead to delayed effectiveness compared with antipsychotics that can be started at therapeutic doses. This problem also may be seen with up-titration of other agents with strong NEα1 properties, including chlorpromazine, clozapine, quetiapine, and risperidone, and should be considered when treating patients who need rapid dose escalation.
Related resource
- Iloperidone (Fanapt) prescribing information. www.fanapt.com/fanapt-pi-may09.pdf.
Drug brand names
- Aripiprazole • Abilify
- Chlorpromazine • Thorazine
- Clozapine • Clozaril
- Droperidol • Inapsine
- Fluoxetine • Prozac
- Haloperidol • Haldol
- Iloperidone • Fanapt
- Ketoconazole • Nizoral
- Methadone • Dolophine, Methadose
- Olanzapine • Zyprexa
- Paliperidone • Invega
- Paroxetine • Paxil
- Pimozide • Orap
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Thioridazine • Mellaril
- Ziprasidone • Geodon
Disclosures
Dr. Weiden receives research support from the National Institute of Mental Health and Ortho-McNeil Janssen. He is a consultant to AstraZeneca, Bristol-Myers Squibb/Otsuka America Pharmaceutical, Eli Lilly and Company, Forest, Ortho-McNeil Janssen, Pfizer Inc., Schering-Plough, Vanda, and Wyeth, and a speaker for Ortho-McNeil Janssen and Pfizer Inc.
Dr. Bishop receives research/grant support from the National Institute of Mental Health, NARSAD, and Ortho-McNeil Janssen.
