SEROQUEL XL® (quetiapine Fumarate Prolonged Release): New Depression And Anxiety Results Presented At IFMAD In Budapest

Main Category: Depression
Also Included In: Anxiety / Stress;  Clinical Trials / Drug Trials
Article Date: 13 Dec 2007 - 2:00 PDT

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The first data from the SEROQUEL XL® major depressive disorder (MDD)1,2 and generalised anxiety disorder (GAD)3 clinical development programmes were presented at the 7th International Forum on Mood and Anxiety Disorders (IFMAD) in Budapest. The data showed that patients who received quetiapine XL experienced significant reductions in symptom severity compared to those on placebo, in each of three trials, which investigated quetiapine XL as monotherapy in MDD1, adjunctive therapy in MDD2 and as monotherapy in GAD3. The data is the first to be released from the AstraZeneca MDD/GAD clinical trial programme, which involves over 7000 patients. Seroquel XL is not currently licensed in the UK and does not currently have licenses for MDD or GAD.

All studies were randomised double blind and in the first study of 612 patients with MDD, quetiapine XL monotherapy showed a significant reduction in total scores on the Montgomery-Åsberg Depression Rating Scale (MADRS)1. After 6 weeks of treatment, scores were reduced for both the 150mg/day dose (14.81; P≤0.001) and the 300mg/day dose (-15.29; P≤0.001) versus placebo (-11.18; P≤0.001). Significant improvement was seen within 8 days of starting treatment (P<0.01) compared with placebo. In an active-control arm, patients who received duloxetine (60mg/day) had significant improvement at Week 6, but no significant response by Day 8 (P=0.3).

Dr Stuart Montgomery, Imperial College School of Medicine, University of London and lead investigator in the MDD study said: "Seroquel has now demonstrated efficacy in unipolar depression and generalised anxiety disorder. All of the doses of Seroquel XL examined in the studies provided improvement in MDD and GAD symptoms and, importantly, Seroquel XL worked quickly, improving symptoms for patients within about a week of starting treatment."

The second study (Phase III), also in patients with MDD examined quetiapine XL as add-on to antidepressants2. After 6 weeks of treatment, MADRS scores were significantly reduced for both the 150mg/day dose (-15.26; P<0.01) and the 300mg/day dose (-14.94; P<0.01) versus placebo (-12.21). Onset of action was rapid, with significant differences from placebo apparent from Week 1 (P<0.001).

The third study (Phase III) in patients with GAD who received quetiapine XL, showed significant improvements on the Hamilton Anxiety scale (HAM-A) 3. Quetiapine XL monotherapy significantly reduced scores after 8 weeks of treatment at doses of 50mg/day (-13.95, P<0.05) and 150mg/day (-15.96, P<0.001) compared with placebo (-12.30). Statistically significant separation from placebo in the HAM-A total score was evident by day 4 with quetiapine XL 50mg/day (P<0.001) and 150mg/day (P<0.05). Patients who received paroxetine (20 mg/day) in an active-control arm of the trial had significant improvement at Week 8 (P<0.01), but not at Day 4.

Data recently presented on the mechanism of action of quetiapine may help explain these findings of antidepressant activity. Abnormal serotonin and norepinephrine activity is believed to mediate key symptoms of depression. The active metabolite of quetiapine inhibits the activity of the norepinephrine transporter (NET), which is an established and important site of therapeutic action for several antidepressant medications. Inhibiting NET leads to elevation of noradrenaline levels in specific areas of the brain, and may be associated with antidepressant effects.4

References

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). Poster 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). Poster 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. Poster presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007

4. Goldstein JM, et al. Unique mechanism of action for the antidepressant properties of the atypical antipsychotic quetiapine. Poster NR336 presented at the American Psychiatric Association 160th Annual Meeting, San Diego, California, 19-24 May, 2007

Notes:

In the rest of the world SEROQUEL XL® is known as SEROQUEL XR(tm). SEROQUEL XL is a trademark of the AstraZeneca group of companies.

The U.S. Food and Drug Administration (FDA) approved SEROQUEL XL, known as XR in the US, in May 2007 for the treatment of schizophrenia in adult patients. The Netherlands regulatory authority Medicines Evaluation Board (MEB) has also approved SEROQUEL XL, and AstraZeneca has applied for a Mutual Recognition Procedure to seek similar approvals across Europe. AstraZeneca has filed for approval to the UK's MHRA under a national licence.

Launched in 1997, Seroquel (quetiapine fumarate, immediate release) 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 FTSE4Good Index.

For more information about AstraZeneca, please visit: http://www.astrazeneca.com

AstraZeneca Press Office: http://www.astrazenecapressoffice.com

The Seroquel SmPC can be found at http://emc.medicines.org.uk/

Media contacts:

Kate Jefferson, AstraZeneca

Daniel Burges, Munro & Forster Communications

Source:
Manmeet Sohal
http://www.munroforster.com