APA: New Drug No Better for Negative Schizophrenia Symptoms

Long-term findings for the novel antipsychotic agent asenapine did not confirm any advantage over second-generation antipsychotics for negative symptoms of schizophrenia.

In a randomized trial, the experimental compound produced the same benefit over 52 weeks as olanzapine (Zyprexa, Zydis) for all measures of both positive and negative symptoms, Nina Schooler, Ph.D., of the State University of New York Downstate Medical Center in New York, and colleagues reported here at the American Psychiatric Association meeting.

Asenapine is one of a new pipeline of antipsychotic agents with lower muscarinic and histaminic receptor affinity, suggesting fewer of the metabolic and other side effects that have plagued second-generation antipsychotics. (See APA: Novel Antipsychotic Promising for Schizophrenia)

The drug is being developed by Schering-Plough for treatment of schizophrenia and bipolar disorder. The company applied for FDA approval on the compound and said it expects a decision before the end of the year.

Earlier in the clinical trials program for asenapine, an unhypothesized benefit turned up -- it appeared to improve negative symptoms of schizophrenia significantly better than risperidone (Risperdal).

These negative symptoms, such as lack of motivation and social withdrawal, are far more likely to persist over time than are the core, positive symptoms of the disorder, "which have a much more waxing and waning form," Dr. Schooler said.

To examine this potential advantage prospectively, the researchers conducted the Aphrodite 25543 study, which included 26 weeks of double-dummy treatment with asenapine (5 to 10 mg bid) or olanzapine (5 to 20 mg qd) in 481 schizophrenia patients who had higher negative than positive symptom scores.

Dr. Schooler's presentation focused on the 26-week extension phase that followed for the 134 asenapine-treated patients and 172 olanzapine-treated patients that remained in the trial.

For the primary outcome of Negative Symptom Assessment Scale 16 scores, there was no significant difference between the drugs at week 52 (P=0.2344).

Likewise, they found no differences -- and little change over time -- for the positive symptom portion of the Positive and Negative Syndrome Scale (PANSS) or for the anxiety and depression portion.

Quality of life also improved similarly for asenapine and olanzapine over the course of the trial (P=0.2838).

Both drugs had a high rate of treatment-emergent adverse events over the total 52-week span of the trial (85.1% for asenapine and 74.1% for olanzapine), although serious treatment-emergent events were less common with the new drug (11.2% versus 4.1%).

The most common adverse events over the entire trial were headache (17.2% versus 11.0%), insomnia (15.7% versus 12.8%), and somnolence (11.9% versus 11.0%), which Dr. Schooler said she didn't believe were dramatically different between drugs.

Weight gain, though, as expected, was substantially higher with olanzapine at 27.9% compared with 6.0% with asenapine (change 4.0 versus ­-1.4 kg, P<0.001).>

Source : www.medpagetoday.com