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Atypical Antipsychotics Offer Equivalent Benefit in First-Episode Psychosis: Presented at ECNP

By Paula Moyer

AMSTERDAM, THE NETHERLANDS -- October 25, 2005 -- All of the atypical antipsychotic agents preserve neurocognitive function in patients with first-episode psychosis, but they differ in minor ways regarding the specific domains that they influence, according to results of the Comparison of Atypicals for First-Episode Psychosis (CAFE) study.

Richard S. E. Keefe, PhD, associate professor of psychiatry and behavioral sciences, Duke University Medical Center, Durham, North Carolina, presented the findings here on October 23^rd at the 18^th Congress of the European College of Neuropsychopharmacology (ECNP).

Dr. Keefe said, "It's important to take these data --- and target individualized medicines for these patients, and make sure all patients have access to all of these medications, because each patient will respond differently."

The study involved 26 centers in the United States and Canada and was designed to compare the antipsychotic agents for patients having a first psychotic episode. An appropriate treatment is critical for such patients because they typically respond well to treatment, but they often discontinue treatment and therefore have recurrent episodes that are less easy to treat, Dr. Keefe said.

The investigators compared the effects of quetiapine (Seroquel), risperidone (Risperdal), and olanzapine (Zyprexa). They evaluated overall effectiveness as measured by all-cause treatment discontinuation in subjects who were 16 to 40 years old and had a diagnosis of first-episode schizophrenia, had psychotic symptoms for 1 month to 5 years, and scores greater than 4 on the Positive and Negative Symptoms Score (PANSS) psychosis subscale.

Subjects were excluded who had a previous psychotic episode from which they recovered and if they had a lifetime history of more than 16 weeks of antipsychotic treatment.

Discontinuation of treatment could be due to an inadequate effect, adverse effects, and patient choice, which consisted of failure to keep appointments, desire to stop medication for personal reasons, and other patient-specific reasons for stopping treatment. Secondary outcomes included PANSS and Clinical Global Impression (CGI) scores, as well as the Calgary Depression Scale for Schizophrenia (CDSS), 2 neurocognitive batteries, and side-effect characterizations.

Subjects underwent the neurocognitive battery of tests at baseline, at week 12, and at week 52. The investigators assessed the cognitive domains of processing speed, reasoning and problem solving, verbal memory, working memory, and vigilance.

There were 134 patients in the quetiapine arm and 133 each in the olanzapine and risperidone arms. The average dose was 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone.

"There was no difference among the drugs in terms of the all-cause discontinuation rate," Dr. Keefe said. "After 1 year of treatment, all 3 of the medications had a pretty high rate of discontinuation, about 70% in all of them. There was no difference in subcategories of reasons for discontinuation, whether it was patient decision or inadequate effect."

The 3 groups had no statistically significant difference in PANSS scores, Dr. Keefe said. However, analysis of the improvement of positive symptoms showed that patients on olanzapine improved more than those on quetiapine. "That was the only difference among the drugs," he said.

The agents were associated with similar results on the CGI and on the CDSS.

Similarly, the agents were associated with similar rates of adverse effects. Dr. Keefe noted that patients on quetiapine were more likely to report dry mouth and somnolence, and those on risperidone were more likely to complain of drooling.

Patients on olanzapine gained an average of 7 km over their baseline weight after 12 weeks and approximately 11.5 km at 1 year. The other 2 agents were associated with less weight gain. Among those treated with olanzapine, 80% gained 7% or more over their baseline weight, compared with 57.6% of those on risperidone and 50% of those on quetiapine.

On neurocognitive tests, results showed no statistically significant difference among the drugs, with a modest improvement in all. However, when the investigators assessed the impact of the medications on different cognitive domains, they saw that quetiapine had a greater effect on verbal fluency and processing speed. Risperidone was associated with a greater improvement in working memory.

Therefore, the results show the importance of tailoring the treatment to the individual patient's needs, Dr Keefe said. "All patients should have access to all of the medications, so that the physician can make the best choice for the individual patient," he said.

CAFE was funded by AstraZeneca, which manufactures Seroquel.


[Presentation title: Comparison of Atypicals in First-Episode Psychosis: A Randomized, 52-Week Comparison of Olanzapine, Quetiapine, and Risperidone. Late-Breaking Session, Abstract 5]

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