HOLLYWOOD, FLA. – An immediate and abrupt switch to iloperidone from another atypical antipsychotic agent provides a markedly greater clinical response rate within the first 2 weeks than does a gradual switch with stepwise dose reduction of the drug being discontinued, according to data from the i-FANS trial.
This superior early clinical response rate comes at the price of a modest increase in dizziness. However, the rates of no other antipsychotic side effects in the Iloperidone Flexible-Dose Study Assessing Efficacy and Tolerability of Two Switch Approaches in Schizophrenia patients, or i-FANS trial, were affected by switching strategy, Dr. Leslie Citrome reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
Dr. Leslie Citrome
The i-FANS study was a multicenter, open-label trial involving 500 adults with schizophrenia randomized to a gradual or immediate switch from risperidone (Risperdal), olanzapine (Zyprexa), or aripiprazole (Abilify) to iloperidone (Fanapt). The switch was made because of inadequate efficacy and/or emergence of tolerability problems with the drug being discontinued.
In the gradual-switch group, the baseline dose of the first antipsychotic was reduced by 50% on day 1 and by 75% after 1 week, with a complete halt of the drug at the end of week 2. In contrast, current therapy was discontinued on day 0 in the immediate-switch group. Patients in both study arms received iloperidone at 1 mg b.i.d. on day 1, titrated over 4 days to 6 mg b.i.d., then further increasing by no more than 4 mg per day up to 12 mg b.i.d. as warranted, explained Dr. Citrome, professor of psychiatry at New York Medical College, Valhalla.
The primary outcome for this analysis was a rating of "much" or "very much" improved on the Integrated Clinical Global Impression of Change (I-CGI-C) at the end of week 2. This endpoint was achieved in 5.4% of the gradual switch and 11.1% of the immediate switch group at week 1, and by 17.5% and 26.1%, respectively, in the two groups at week 2. The significant advantage favoring the immediate switch strategy was similar in magnitude across the individual subgroups switching from risperidone, olanzapine, and aripiprazole.
The most common treatment emergent adverse event seen in i-FANS was dizziness. The incidence was significantly lower in the gradual-switch group during week 1, at 8.8% compared to 14.2% in the immediate-switch group. The rate during week 2 was 1.3% in the gradual- and 3.2% in the immediate switch group during week 2.
Iloperidone is a mixed dopamine D2, serotonin 5HT-2A, and alpha-adrenergic antagonist approved for the treatment of schizophrenia.
The i-FANS study was supported by Novartis. Dr. Citrome reported receiving research support and/or consulting fees from Novartis and 17 other pharmaceutical companies.