By Walter Alexander
COLORADO SPRINGS—A new atypical antipsychotic medication, bifeprunox (Solvay), currently under FDA final review, has shown good efficacy in 2 studies of patients with schizophrenia being treated for acute exacerbations or maintenance of stable disease, investigators reported at the International Congress for Schizophrenia Research. The major advantage of this agent appears to be a more benign side-effect profile than that common to other atypical and typical antipsychotic agents.
"The main point is that bifeprunox has probably the most benign side-effect profile of any of the atypical antipsychotic agents, and certainly is more benign than the typical agents," said Herbert Y. Meltzer, MD, professor of psychiatry, Vanderbilt University Medical Center, Nashville.
Bifeprunox is a highly-potent partial dopamine D2 agonist with moderately-potent serotonin 5-HT1A agonist activity. Its lack of affinity for 5-HT2A and 5-HT2C, muscarinic or histaminergic receptors, accounts for an absence of the cardiometabolic symptoms (ie, weight gain, adverse lipid changes) and extrapyramidal symptoms (tardive dyskinesia) common to other atypical and typical antipsychotic agents, said Dr Meltzer.
In this double-blind study, patients (mean age, 38 years) meeting the Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia who had an acute exacerbation of the disease were randomized to once-daily bifeprunox (30 or 40 mg/d; n = 148 for each), risperidone (Risperdal) 6 mg/day (n = 154), or placebo (n = 148) for 6 weeks.
All patients were hospitalized for a minimum of 10 days after randomization. The primary efficacy end point was the change in Positive and Negative Syndrome Scale (PANSS) score compared with baseline.
Significant decreases in PANSS scores versus baseline were seen with use of bifeprunox 30 mg and with risperidone at each weekly assessment. Dr Meltzer noted that the greater efficacy improvement with risperidone (an approximate 19-point drop in PANSS score vs about a 13-point drop with bifeprunox) was unlikely to be clinically significant. The dropout rate for lack of efficacy was similar in the 2 groups.
The most striking differences between the 2 groups were the changes in weight and lipids.
Patients in the bifeprunox (30-mg) group lost approximately 1 kg ( = .001 vs placebo), while those in the risperidone (6-mg) group gained nearly 1.5 kg ( = .003 vs placebo); those taking placebo gained a clinically insignificant amount of weight.
Mean plasma glucose dropped nearly 5 mg/dL with bifeprunox and increased by more than 1 mg/dL with risperidone. Similarly, plasma prolactin levels decreased significantly with bifeprunox and increased significantly with risperidone.
Second Study, Similar Results
In the second trial, approximately 500 stable patients with schizophrenia received bifeprunox 20 or 30 mg/day or placebo for 6 months. The primary end point of time to deterioration was significantly prolonged with both doses of bifeprunox compared with placebo, said Michel Bourin, MD, of the University de Nantes, Nantes, Cedex, France. Risk of deterioration was 1.5 times greater in the placebo group. Significantly more patients deteriorated in the placebo group (59%) than in the bifeprunox groups (41% with 20 mg; 38% with 30 mg).
Weight loss was significantly greater with the active drug (30 mg) compared with placebo. The incidence of the metabolic syndrome trended upward in the placebo group and downward in the 2 bifeprunox groups.
Reviewing both studies, Dr Meltzer told IMWR, "Because efficacy is essentially the same among the atypical antipsychotic agents, I think most physicians and patients make treatment decisions based on side-effect profile. With schizophrenia occurring in 1% of the population, there's a huge number of people who will find this drug as effective as anything else they can receive, and certainly more tolerable."
Dr Meltzer noted that, once approved, the bifeprunox recommended dose will be 20 mg/day. More than 2 million people in the United States have schizophrenia.