The first data from the SEROQUEL XR™ (quetiapine fumarate) Extended Release clinical development programme in major depressive disorder (MDD)1,2 and generalised anxiety disorder (GAD)3 were presented at the 7th International Forum on Mood and Anxiety Disorders (IFMAD) in Budapest, AstraZeneca announced today. The data showed that patients who received SEROQUEL XR once daily experienced significant reductions in symptom severity compared to those on placebo in each of three trials, which investigated SEROQUEL XR as monotherapy in MDD,1 adjunctive therapy in patients with MDD2 with inadequate response to antidepressant therapy, and as monotherapy in GAD.3 These studies are part of a clinical development programme that involved over 7000 patients - one of the largest conducted in depression and anxiety. SEROQUEL® and SEROQUEL XR™ are not approved for the treatment of MDD or GAD.
Reductions in symptom severity were measured by improved (lowered) symptom scale scores. Two randomised, double-blind Phase III studies in MDD reported significantly reduced total scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 6 weeks of treatment with once daily SEROQUEL XR. In the MDD monotherapy study, mean MADRS score was significantly improved for patients receiving SEROQUEL XR 150 mg (-14.81; p
Dr Stuart Montgomery, Imperial College School of Medicine, University of London and author of the MDD monotherapy study said: "These study results are remarkable - all of the doses of SEROQUEL XR examined provided improvements in MDD and GAD symptoms. Results from further studies that are still ongoing will add to our understanding of SEROQUEL XR in these conditions."
In all three studies presented at IFMAD, SEROQUEL XR was generally well tolerated. The most common adverse events across all of the doses examined (50-300 mg/day) were dry mouth (15.9-38.2%), sedation or fatigue (13.2-38.8%), somnolence (16.8-27%) and dizziness (9.2-19.1%). The numbers of patients with blood glucose elevated above 126 mg/dL at study end for SEROQUEL XR 150 mg, 300 mg and placebo, respectively, were 2.9%, 6.3% and 0.9% in the MDD monotherapy and 3.2%, 6.3% and 3.3% in the adjunctive therapy study. In the GAD study the elevation was seen in 1.1% of patients (50mg SEROQUEL XR), 0.6% (150mg SEROQUEL XR) and 1.7% (placebo).
Martin Brecher, Executive Director Medical Science, AstraZeneca said: "The data are very encouraging and suggest SEROQUEL XR has the potential to provide a new treatment choice in this area particularly among patients who fail antidepressant therapy with existing treatment. The study program not only covers adjunct treatment but extended also to monotherapy. New therapy options are needed for treating MDD and GAD because currently available antidepressants do not achieve symptom remission in a substantial proportion of patients. Over the coming months and years we will learn more about how far an antipsychotic like SEROQUEL XR may provide a new option for these patients. AstraZeneca plans regulatory submissions in 2008."
Recently presented data may help to explain the study data in MDD and GAD alongside SEROQUEL's known efficacy in bipolar depression. A pre-clinical study used brain imaging with positron emission tomography (PET) to investigate the mechanism of action of SEROQUEL® in non-human primates.4 SEROQUEL (quetiapine fumarate), both directly and indirectly (via its major active metabolite norquetiapine), was found to target the dopamine D2 and the serotonin 5-HT2A receptors in the brain at blood concentrations similar to those during treatment with clinically recommended doses of SEROQUEL in humans. Additionally, SEROQUEL's major active metabolite norquetiapine was shown to target NET - the transporter for norepinephrine (noradrenaline). Inhibition of NET elevates norepinephrine (noradrenaline) levels in specific areas of the brain, an effect that is associated with antidepressant action.
Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 25 million* patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 77 countries for the treatment of bipolar mania, and in 11 countries including the USA for the treatment of bipolar depression. SEROQUEL XR was launched for the treatment of schizophrenia in the US in 2007, and its clinical development program and planned regulatory filings extend through bipolar disorder to major depressive disorder (MDD) and generalised anxiety disorder (GAD).
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 FTSE4Good Index.
SEROQUEL XR™ and SEROQUEL® are trademarks of the AstraZeneca group of companies.
1. Montgomery S, et al. A randomised, placebo-controlled study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
2. Bauer M, et al. Results from a phase III study of extended release quetiapine fumarate (quetiapine XR) as add-on to antidepressants in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
3. Bandelow B, et al. Results from a phase III study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalised anxiety disorder. Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007
4. Nyberg S et al. PET-measured D2, 5-HT2, and NET occupancy by quetiapine and N-desalkyl-quetiapine in non-human primates. Presented at the European Congress of Neuropsychopharmacology, Vienna, Austria, 13-17 October, 2007
*This estimate is based upon: (1) assumptions as to persistence (the number of prescriptions per patient) based upon 2002 market research; and (2) projections of prescriptions since launch based upon information available in the US and 13 of the 50 other countries in which SEROQUEL is marketed.
For further information, please visit http://www.astrazeneca.com or http://www.astrazenecapressoffice.com.
What is Anxiety?For more information on what anxiety is and what to do about it, please see:
What is Anxiety? What Causes Anxiety? What To Do About It.