According to study results presented at the 2007 American Psychiatric Association annual meeting, iloperidone, an investigational atypical antipsychotic, was shown to have a favorable akathisia profile.
Akathisia – a debilitating sensation of restlessness that manifests as an inability to sit still – is a frequent side effect of antipsychotic medications. Iloperidone is being studied by Vanda Pharmaceuticals Inc., a biopharmaceutical company working to advance the science of personalized medicine.
“Many people who have akathisia will say that it is the worst experience in their life, and at its worst it can even lead to suicidal behavior given its severity. It is not a surprise that akathisia can lead to medication discontinuation, leading to further symptoms and relapse,” said Peter Weiden, M.D., Director of the Psychosis Program of the Department of Psychiatry at the University of Illinois at Chicago. “Many of the newer medications have less akathisia than older antipsychotics, but it is still a significant problem. These findings suggest that iloperidone has a very low akathisia profile, which is positive news for patients with schizophrenia, and the physician community.”
Akathisia was assessed in a Phase III trial conducted by Novartis, in which 706 patients were studied over six weeks at two dose ranges of iloperidone (12-16 mg/d, 20-24 mg/d) with placebo and risperidone controls (6-8 mg/d). When akathisia was measured on the Barnes Akathisia Scale (BAS), the iloperidone groups had fewer patients whose total akathisia score worsened (12%, p=0.04; 8%, p=0.004), compared to placebo (20%). The risperidone group (20%, p=1.00) was equal to placebo.
Three times as many patients in the risperidone group (22%), compared to placebo (7%), received anticholinergic medication to manage intolerable extrapyramidal symptoms (EPS) (such as tremor, slurred speech, restlessness and involuntary muscle movement) during the course of the study. In contrast, 5% of low-dose and 11% of high-dose iloperidone patients received anticholinergic medication.
“Iloperidone may be less likely to worsen akathisia because of its novel mechanism of action,” said Paolo Baroldi, M.D., Ph.D., Chief Medical Officer, Vanda Pharmaceuticals Inc. “Akathisia is believed to be due to D2 activation, which is not present with iloperidone.”
In this Phase III randomized, double-blind, placebo- and risperidone-controlled, international multi-center six-week study conducted by Novartis, patients were randomized to one of four treatment groups: iloperidone low-dose (12-16 mg/d, n=244), iloperidone high-dose (20-24 mg/d, n=145), risperidone (6-8 mg/d, n=157) or placebo (n=160).
Patients enrolled in the study were 62% male (n=435) and 38% female (n=271), approximately 39 years of age, and had a diagnosis of schizophrenia or schizoaffective disorder with a Positive and Negative Syndrome Scale (PANSS) score =60 at baseline.
Anticholinergic drugs for the treatment of EPS were permitted during the two-day placebo run-in period. EPS must have improved and anticholinergics discontinued for more than 24 hours prior to baseline measurement.
Changes in akathisia were measured weekly by the BAS and the Extrapyramidal Symptom Rating Scale (ESRS) from baseline to the six-week end point for patients in all treatment groups. Categorical analysis was conducted to determine the percentage of patients with akathisia that worsened, remained unchanged, or improved, from baseline, during the treatment period. Use of anticholinergics (benztropine or biperiden) was allowed during the double-blind phase in all four groups for treatment-emergent EPS, after assessment was completed by the EPS rating scales.