A trial evaluating gradual- or immediate-switch strategies from risperidone, olanzapine, or aripiprazole to iloperidone in patients with schizophrenia

• Published in: Schizophrenia research Vol. 153; no. 1; pp. 160 - 168
• Main Authors: Weiden, Peter J, Citrome, Leslie, Alva, Gus, Brams, Matthew, Glick, Ira D, Jackson, Richard, Mattingly, Greg, Kianifard, Farid, Meng, Xiangyi, Pestreich, Linda, Hochfeld, Marla, Winseck, Adam
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.2014; Elsevier
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Analysis of Variance; Antipsychotic Agents - therapeutic use; Aortic Bodies - drug effects; Aripiprazole; Benzodiazepines; Biological and medical sciences; Clinical improvement; Cohort Studies; Drug Administration Schedule; Drug Substitution - methods; Female; Humans; Iloperidone; Isoxazoles; Male; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Piperazines; Piperidines; Psychiatric Status Rating Scales; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Quinolones; Risperidone; Safety; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - metabolism; Surveys and Questionnaires; Switch strategy; Tolerability; Treatment Outcome; Young Adult; Schizophrenia; Switch strategy; Tolerability; Safety; Clinical improvement; Iloperidone; Partial agonist; Dibenzodiazepine derivatives; Atypical antipsychotic; Olanzapine; Neuroleptic; Psychotropic; Quinolinone derivatives; Serotonine receptor; Aripiprazole; Psychosis; 5-HT1A Serotonine receptor; Risperidone; Benzisoxazole derivatives; 5-HT2A serotonin receptor; Human; Dopamine antagonist; Serotonin antagonist; Thienobenzodiazepine derivatives; D2 Dopamine receptor; Strategy
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2013.11.042

Abstract In a 12-week randomized open-label trial, adults diagnosed with schizophrenia experiencing inadequate efficacy and/or poor tolerability on risperidone, olanzapine, or aripiprazole were randomized to switch to iloperidone either gradually (ie, down-titration of current therapy over the first 2 weeks [to 50% on Day 1, 25% by Week 1, 0% by Week 2]) or immediately. All patients were titrated on iloperidone to 6 mg BID by Day 4, then flexibly dosing between 6 and 12 mg BID, as needed. The primary variable was the Integrated Clinical Global Impression of Change (I-CGI-C) and the primary analysis time point was Week 12. A total of 500 patients were randomized and received iloperidone (gradual switch, 240; immediate switch, 260), with 175, 155, and 170 patients switched from risperidone, olanzapine, and aripiprazole, respectively. I-CGI-C Results confirmed improved outcomes at Week 12, with scores that were similar between the gradual- and immediate-switch groups, respectively, for risperidone, 2.82 and 2.67 (95% CI: − 0.229, 0.511); olanzapine, 2.87 and 3.03 (95% CI: − 0.548, 0.235); and aripiprazole, 2.79 and 2.81 (95% CI: − 0.405, 0.368). Incidence of adverse events (AEs) was similar in both switch groups, with the most frequently reported (≥ 10%) being dizziness, dry mouth, somnolence, and weight increase. In conclusion, switching to iloperidone by either a gradual or an immediate method did not reveal any clinically significant differences in ratings of overall efficacy and safety/tolerability outcomes, based on the I-CGI-C at 12 weeks. Similar overall safety/AE profiles were observed regardless of the specific agent from which patients were switched.