BOLDER II, an eight week, multi-centre, placebo-controlled study, reinforces the findings of the landmark BOLDER I study2 published in American Journal of Psychiatry in July 2005, which first indicated a significant effect for SEROQUEL in treating major depressive episodes associated with bipolar disorder.
In BOLDER II, the significant reduction in MADRS total score was seen both in patients with bipolar I and bipolar II disorder, in patients with or without a rapid cycling course of illness, and as early as week one after randomisation. Significant improvements were also seen compared with placebo in the various secondary study endpoints among SEROQUEL-treated patients, including reduction of anxiety symptoms. In addition, more than half (53%) of patients receiving SEROQUEL achieved remission** from their bipolar depression symptoms.
Importantly, SEROQUEL was shown to be well tolerated in BOLDER II with a similar safety profile seen to that in BOLDER I. The rate of serious adverse events was low and comparable in all treated groups. The most common adverse events reported in the trial were dry mouth, sedation, somnolence, dizziness and constipation, and there was a low incidence of treatment-emergent mania in the SEROQUEL-treated groups.
As in BOLDER I, there was a low incidence of EPS (extrapyramidal symptoms) and minimal weight change reported in the study.
* MADRS (Montgomery- Åsberg Depression Rating Scale) measures the severity of a number of depressive symptoms including mood and sadness, tension, sleep, appetite, energy, concentration, suicidal ideation and restlessness. The MADRS score decreases as depression symptoms improve.
** Remission defined as a score of less than 12 on the MADRS scale (Montgomery-Asberg Depression Rating Scale) at any point in time during the study
Professor Joseph Calabrese, co-director of the National Institute of Mental Health Bipolar Research Center at University Hospitals of Cleveland and Case Western Reserve University says: "Patients with bipolar depression are underserved and understudied. The findings from the BOLDER II study are very encouraging and support the findings of BOLDER I, in showing the potential of SEROQUEL, as monotherapy, for the acute treatment for bipolar depression. Each of these two studies represent the largest placebo-controlled short-term studies ever conducted in bipolar depression. The beneficial risk:benefit profile of Seroquel seen in both studies could offer an important therapeutic value for both patients and physicians as we currently have only one FDA-approved therapy to treat depressive episodes associated with bipolar disorder."
Bipolar disorder is a serious mental illness that affects approximately 3-4% of the adult population and is the sixth leading cause of disability in the world.3,4,5,6 Patients with bipolar disorder are symptomatic almost half of their lives, and approximately two-thirds of that time is spent in the depressed phase of the illness.7 Currently SEROQUEL is only approved for the treatment of mania associated with bipolar disorder.
"BOLDER II shows that SEROQUEL may provide substantial clinical benefits to patients with bipolar disorder", commented Carolyn Fitzsimons, Seroquel Commercial VP. "Based on prior discussions with the FDA and the results of BOLDER II, AstraZeneca plans to file for a US licence extension for SEROQUEL in the treatment of depressive episodes associated with bipolar disorder around the end of this year (2005)."
SEROQUEL has been licensed for the treatment of schizophrenia since 1997 and is available in 85 countries for the treatment of this condition. SEROQUEL is also licensed in 73 countries for the treatment of mania associated with bipolar disorder.
All product names appear in upper case. SEROQUEL is a trademark of the AstraZeneca group of companies.
SEROQUEL is currently not licensed for the treatment of bipolar depression.
BOLDER II was an eight week, multi-centre, placebo-controlled trial conducted in the US which evaluated the efficacy of SEROQUEL (quetiapine) treatment at doses of 300 or 600mg in over 500 patients with bipolar disorder experiencing major depressive episodes. In BOLDER, the primary endpoint for bipolar depression was change in baseline on the MADRS (Montgomery- Åsberg Depression Rating Scale). Bipolar depression and anxiety symptoms were assessed using the MADRS, HAM-D (Hamilton Rating Scale for Depression) and HAM-A (Hamilton Rating Scale for Anxiety Scale).
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 over $21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology and neuroscience products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. In Neuroscience, AstraZeneca is dedicated to providing medicines that have the potential to change patients' lives. The company already markets several products including SEROQUEL and ZOMIG. SEROQUEL, which has proven efficacy and a very favourable side effect profile, is the fastest growing of the leading atypical antipsychotics and the number one prescribed atypical in the United States with global sales of $2 billion in 2004; ZOMIG is a reliable migraine therapy and a leader within the triptan market. The Neuroscience pipeline includes leading approaches for the treatment of depression and anxiety, overactive bladder, dementia, stroke, pain control and anaesthesia.
Further Information:
For further information, please go to www.astrazenecapressoffice.com or please contact:
Louise Marland at AstraZeneca
Tel: +44 (0) 1625 510782
Mobile +44 7900 607 794
louise.marland@astrazeneca.com
Julie Saunders at AstraZeneca
Tel: +44 (0) 1625 231319
Mobile: +44 (0) 7810 528 368
Julie.Saunders@astrazeneca.com
References:
1. BOLDER II study. AstraZeneca Data on File.
2. Calabrese JR et al. Am J Psychiatry 2005;162:1351–60.
3. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC, American Psychiatric Association, 2000:385;395.
4. Hirschfield et al. Screening for bipolar disorder in the community J Clin Psychiatry. 2003:64;53-59
5. Lish JD, Dime-Meenan S, Whybrow PC et al. The National Depressive and Manic-Depressive Association (DMDA) survey of bipolar members. J Affect Disord. 1994:31;281-294.
6. World Health Organization and the World Bank. The Global Burden of Disease: Summary. Cambridge, Mass: The Harvard School of Public Health Harvard University Press, 1996.
7. Judd, Lll, Akiskal, HS, Schettler, PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar disorder. Arch Gen Psychiatry. 2002;59:530-537.