Second-Generation Antipsychotics Equally Effective in Schizophrenia

Larry Schuster

July 01, 2005

June 30, 2005 (Vienna) — In the first head-to-head trial of three leading second-generation antipsychotics for patients with first-episode schizophrenia, researchers found that the three drugs were nearly equal on all measures of response and drop-out rates, according to findings presented here at the 8th World Congress of Biological Psychiatry.

The CAFÈ (Comparison of Atypicals in First Episode Psychosis) study was conducted by the University of North Carolina at Chapel Hill and involved investigators at 26 U.S. sites.

Christine E. Marx, MA, MD, assistant professor, department of psychiatry and behavior sciences, Duke University Medical Center, Durham, North Carolina, presented preliminary results on behalf of Jeffrey Lieberman, MD, CAFÈ principal investigator and chairman of psychiatry at Columbia University College of Physicians and Surgeons in New York, NY, and director of the New York State Psychiatric Institute in New York City.

The study was conducted for 52 weeks, and the researchers compared the mean modal doses of 11.7 mg per day of olanzapine (Zyprexa) in 133 patients, 506 mg per day of quetiapine (Seroquel) in 134 patients, and 2.4 mg per day of risperidone (Risperdal) in 133 patients.

At least 73% of the patients in each group had not received any previous treatment. All patients had either schizophrenia, schizophreniform disorder, or schizoaffective disorder, and the mean duration of the disease was 11 to 15 months. The mean age of the study group was 24 to 25 years old, and about 75% were male.

The primary endpoint was all-cause treatment discontinuation. Dr. Marx told Medscape that about 65% to 70% of patients in each treatment group dropped out by the end of the 52 weeks.

The response rate was the secondary endpoint, and each drug achieved at least a 60% response rate on combined measures of the Positive and Negative Syndrome Scale and on the Clinical Global Impression scale.

Sexual dysfunction was the most common adverse effect seen in the trial, affecting about 60% of patients. The most serious adverse effects were two suicide attempts among the olanzapine group, one attempt in the risperidone group, and two suicides in the quetiapine group. Dr. Marx said that she did not know how the rate of suicide and attempted suicide in study patients would compare with a group of similar patients who had not received treatment, but that study patients generally did have an increased risk of suicide and attempted suicide.

As seen in previous studies, weight gain was an adverse effect in the olanzapine group. Also the quetiapine group required less medications to deal with Parkinson symptoms and akathisia than the other groups, though the incidence of those complaints seemed similar, Dr. Marx said.

Another benefit of the study was the realization that the dose of quetiapine that is commonly used in practice is probably too low for patients with schizophrenia, Dr. Marx told Medscape.

"The likely dose of quetiapine needs to be higher than what is typically used in clinical practice," Dr. Marx said, noting that chronic patients usually receive 500 mg per day or less. The rule of thumb, however, is that chronic patients generally ought to receive about double the dose that is given to patients with first-episode schizophrenia who tend to respond better to smaller doses. Based on this study, chronic patients ought to be receiving about 1,000 mg per day of quetiapine.

The final dosing in this study was arrived at by a protocol that allowed physicians to increase the dosing every 48 hours as warranted by the physician's determination of tolerability and efficacy of the drug, Dr.Marx said. Ultimately, 506 mg per day was found to provide a level of efficacy that was equivalent to the other two drugs, whose therapeutic dosing had been previously well established, Dr. Marx said.

She also stated that separate studies are underway to confirm whether 1,000 mg per day is the proper dosing for chronic patients, but clinicians who work with the drug expect that 1,000 mg is to be set as the proper dosing for chronic patients.

AstraZeneca, the maker of quetiapine, conducted the CAFÈ study in collaboration with the University of North Carolina.

8th WCBP: Symposium S-070: Novel Mechanisms of Action and Development Strategies for Antipsychotic Drugs. Presented June 29, 2005.

Reviewed by Gary D. Vogin, MD