Sustained-release quetiapine significantly improves symptoms of schizophrenia and time to relapse when initiated in a three-step dose increase to reach effective dose range by the second day of once-daily treatment, according to a presentation at the 2007 European Congress of Psychiatry.

Study 132 randomized 588 patients with acute schizophrenia to the sustained release formulation (400 mg/day, 600 mg/day, or 800 mg/day) or placebo; researchers found significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline for all doses.

After 6 weeks of treatment, reductions of 24.8, 30.9, and 31.3 points were seen with 400, 600, and 800 mg doses, respectively, compared with a reduction of 18.8 points for placebo. Patients on the sustained release formulation also had significantly better scores on the Clinical Global Impression (CGI)-Severity scale and significantly more patients showed improvement on the CGI-Improvement scale than on placebo.

A second study (Study 004) examined time to first psychiatric relapse in 197 patients with clinically stable schizophrenia who were randomized to the sustained release formulation (mean dose, 669 mg/day) or placebo. Patients treated with the sustained release formulation experienced a significantly reduced risk of relapse (risk reduction of 87 percent), and a significantly longer time to relapse compared with patients treated with placebo.

Differences in relapse rate between active treatment and placebo were large enough to require the study to be stopped early, in accordance with study protocol. In the sustained release group, the estimated risk of relapse after 6 months was 14.3 percent versus 68.2 percent in the placebo group. Hospitalization due to worsening of schizophrenia was required by 8.3 percent of placebo patients but no quetiapine patient.

Professor Rene Kahn, Professor and Chair of the Department of Psychiatry and Head of the Division of Neuroscience at the University Medical Center, Utrecht, said: "In these studies [SEROQUEL(R)] sustained release formulation showed its potential as a once-daily treatment for both acute and clinically stable schizophrenia. Statistical significance on the primary endpoint was seen at doses between 400 and 800 mg/day and patients achieved that range within two days of starting treatment - that is an advantage over original formulation quetiapine, where the initial dose escalation is not so simple. In mental healthcare, striving for treatment that is simpler and more practical is an important objective for patients and doctors."

In both studies, somnolence and dizziness were the most common adverse events with the sustained release formulation and these were generally mild or moderate, transient, and did not lead to withdrawal from the trials. The incidence of extrapyramidal adverse events was similar to that for placebo (5.1 percent for placebo versus 2.7 percent [400mg], 8.0 percent [600mg] and 4.1 percent [800mg] of patients taking the sustained release formulation in the acute study).