'Cold Turkey' Switch to Iloperidone From Other Atypicals Safe, Effective

Nancy A. Melville

November 11, 2012

SAN DIEGO, California — Schizophrenia patients who fail to respond to or tolerate atypical antipsychotic medications can safely switch to iloperidone (Fanapt, Novartis) and will likely see improvements in efficacy, new research shows.

"Many clinicians don't realize that iloperidone has such an excellent EPS [extrapyramidal side effects] and akathisia profile," said Peter Weiden, MD, a psychiatrist with the University of Illinois at Chicago Medical Center and a lead investigator in the research.

"Even at effective doses, it's very unlikely to cause akathisia or parkinsonism," he said.

Dr. Weiden presented the research here at Psych Congress 2012: US Psychiatric and Mental Health Congress.

Iloperidone, a mixed D and 5-HT antagonist that was approved by the FDA in 2009 for the treatment of schizophrenia in adults, has a notably favorable profile in terms of side effects. It has been associated with levels of akathisia that are close to those seen with placebo and that are comparable to those reported with quetiapine. The drug is also similar to quetiapine (Seroquel, AstraZeneca) in terms of having a low risk for EPS.

However, switching medications can be tricky and carries important titration issues, particularly with a volatile condition such as schizophrenia.

Immediate vs Gradual Switch

In evaluating possible strategies for safely switching from antipsychotic drugs risperidone, olanzapine, or aripiprazole to iloperidone, Dr. Weiden and colleagues evaluated 2 switching strategies: a gradual switch with some overlap between the 2 drugs, and an immediate switch from the previous drug to iloperidone.

The research on switching involving the 3 drugs was part of the Iloperidone Flexible-Dose Study Assessing Efficacy and Safety and Tolerability of Two Switch Approaches in Schizophrenia Patients (iFANS) trial.

The study involved 500 patients, including 170 who were switched to iloperidone from aripiprazole, 175 who were switched from risperidone, and 155 who were switched from olanzapine.

In addition to being evaluated with respect to their switching approach, the patients were also assessed regarding the reason for switching, including those switching due to suboptimal efficacy, defined as an Efficacy Clinical Global Impression of Change (E-CGI-C) score of 4 (moderately ill) or 5 (markedly ill), or those switching due to side effects, including akathisia, EPS, increased prolactin, weight gain, somnolence/sedation, or agitation.

Interestingly, the efficacy results for patients in the immediate switch-over groups experienced improvement that was about the same as the improvement experienced by the gradual switch group among those switching from olanzapine.

Improvement was greater in the immediate switch-overs from aripiprazole, and much greater at all of the biweekly time points for the patients switching from risperidone.

Surprise Findings

"What we found was surprising — one would logically assume that there would likely be a better overall outlook in gradually titrating between the 2 drugs," Gus Alva, MD, lead investigator on the risperidone section of the study, told Medscape Medical News.

"But it turns out that from an efficacy perspective, the individuals who immediately switched actually fared better, and we saw about the same thing with safety," said Dr. Alva, of ATP Clinical Research, in Costa Mesa, California.

There were few adverse event reports in the 3 drug groups, and improvements in EPS issues were also seen in all 3 of the drug switch-over groups, regardless of whether the switch was immediate or gradual, as reflected in safety and tolerability CGI-S scores.

"If a clinician has a patient who is being treated with an antipsychotic medication for schizophrenia and is struggling with EPS and akathisia issues and is thinking about changing medications, I would recommend considering iloperidone for that patient," Dr. Weiden told Medscape Medical News.

"People tend to focus a lot on metabolic and dyslipidemia and medical problems, but it's important to remember that these medications still to some extent can cause devastating neurological problems," he noted.

"It's better than it was, but it's far from fixed, and is still a big problem that clinicians should think about."

The research was supported by Novartis Pharmaceuticals Corp. Dr. Weiden's disclosures include that he has received grant support or served as a consultant or speaker for Janssen, Novartis, Sepracor/Sunovio Pharmaceuticals, Merck, Eli Lilly, Otsuka America Pharmaceutical, and Roche. Dr. Alva's disclosures include relationships with Novartis, Pfizer, Otsuka, Sanofi-Aventis, and Forest Pharmaceuticals

Psych Congress 2012: US Psychiatric and Mental Health Congress. Abstracts 126, 226, 227. Presented November 9 and 10, 2012.