Seroquel® (Quetiapine) Sustained Release Schizophrenia Data Show Relapse Prevention

Main Category: Schizophrenia
Also Included In: Psychology / Psychiatry;  Mental Health
Article Date: 19 Mar 2007 - 10:00 PDT

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AstraZeneca today announced clinical trial data presented at the European Congress of Psychiatry (ECP) in Madrid that found the once-daily quetiapine sustained-release formulation treatment effective and well tolerated in patients with schizophrenia. The trial results presented demonstrated that the quetiapine sustained release formulation significantly improved symptoms associated with schizophrenia1 and reduced the time to psychiatric relapse2.

Quetiapine sustained release formulation is under review by regulatory authorities around the world for the treatment of schizophrenia and has not yet been approved in any market.

A randomized, double-blind study of 588 patients with acute schizophrenia (Study 132) compared quetiapine sustained release formulation (400 mg/day, 600 mg/day or 800 mg/day) with placebo and found a significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline for all doses.1 After 6 weeks of treatment, reductions of 24.8 (p=0.03), 30.9 (p<0.001), and 31.3 (p<0.001) points were seen with 400, 600, and 800 mg doses, respectively, compared with a reduction of 18.8 points for placebo. Patients on quetiapine (600 & 800mg/day) 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 compared to placebo.

A second randomized, double-blind placebo controlled study (Study 004) examined psychiatric relapse in 197 patients with clinically stable schizophrenia treated with either quetiapine sustained release formulation (mean dose 669 mg/day) or placebo2. Patients treated with quetiapine sustained release formulation experienced a significantly reduced risk of relapse (risk reduction of 87%, p<0.0001), and a significantly longer time to relapse, compared with those on placebo. Treatment effectiveness was large enough to require the study to be stopped early, in accordance with the study protocol. In the quetiapine sustained release group, the estimated risk of relapse after 6 months was 14.3% versus 68.2% in the placebo group (p<0.001). Hospitalization due to worsening of schizophrenia was required by 8.3% of patients on placebo, but was not needed for any patients taking quetiapine sustained release formulation.

Professor Mohan George of the Queen Elizabeth Psychiatric Hospital Birmingham: "In these studies quetiapine sustained release formulation was effective as a once-daily treatment for both acute and clinically stable schizophrenia. Patients responded well to doses between 400 and 800 mg. It is worth noting that a greater separation on endpoints was seen at 600 and 800mg in study 132, and the average dose in study 004 was 669mg/day. In mental healthcare, a choice of formulations is vitally important to provide doctors and patients with additional flexibility and choice of treatment administration."

In both studies, somnolence and dizziness were the most common adverse events with quetiapine sustained release formulation and these were generally mild or moderate, transient, and did not generally lead to withdrawal from the trials. The incidence of extrapyramidal adverse events was similar to placebo (EPS-related adverse events were seen in 5.1% of patients taking placebo versus 2.7% [400mg], 8.0% [600mg] and 4.1% [800mg] of patients taking quetiapine sustained release formulation in the acute study1.

Other new quetiapine sustained release formulation studies presented at the congress show that patients who are inadequately treated with another antipsychotic agent, can be effectively switched to quetiapine sustained release formulation. Among patients who switched to quetiapine sustained release formulation from other antipsychotics, 62.8% achieved improved clinical benefit regardless of the reason for switching (insufficient efficacy or intolerability) (Study 147) 4.

Based on these data and data from other trials, regulatory filings for the treatment of schizophrenia with quetiapine sustained release formulation were submitted to the authorities in the US, EU and other markets in 2006." Beyond schizophrenia, ongoing clinical studies of quetiapine sustained release formulation cover bipolar disorder, major depressive disorder and generalized anxiety disorder.

Quetiapine (original formulation) is the number 1 prescribed atypical antipsychotic in the United States and global sales for quetiapine reached $3.4 billion in 2006. It is licensed in 85 countries for the treatment of schizophrenia, in 73 countries for the treatment of mania associated with bipolar disorder, and in October 2006 it was approved in the US by the FDA for the treatment of bipolar depression.

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index.

References

1. Kahn R, et al. Efficacy and tolerability of once daily quetiapine sustained release in patients with acute schizophrenia: a randomised, double blind, 6 week, placebo-controlled study. Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.

2. Peuskens J, et al. Randomised, placebo-controlled, relapse-prevention study with once-daily quetiapine sustained release in patients with schizophrenia. Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.

3. Möller H-J, et al. Continued efficacy and tolerability in clinically stable patients switched from quetiapine immediate release (IR) to quetiapine sustained release (SR). Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.

4. Ganesan S, et al. Clinical benefit of switching patients with schizophrenia to once-daily quetiapine sustained release. Presented at the European Congress of Psychiatry, Madrid, Spain, 17-21 March, 2007.

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