FDA Approves Astrazeneca's Seroquel For Maintenance Treatment In Bipolar Disorder

Main Category: Bipolar
Also Included In: Regulatory Affairs / Drug Approvals;  Psychology / Psychiatry
Article Date: 16 May 2008 - 2:00 PDT

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AstraZeneca announced that the U.S. Food and Drug Administration (FDA) has approved SEROQUEL® (quetiapine fumarate) for the maintenance treatment of patients with bipolar I disorder, as adjunct to lithium or divalproex. SEROQUEL is approved by the FDA for the treatment of schizophrenia, and is also the only single agent approved by the FDA for the treatment of both depressive episodes in bipolar disorder and acute manic episodes associated with bipolar I disorder1,2.

Considered one of the most severe forms of mental illness2, bipolar disorder currently affects about 8 million adults in the US3-5. Bipolar I disorder is a lifelong psychiatric condition characterized by manic or mixed mood episodes, interspersed with episodes of major depression6. It is estimated that 0.4 percent to 1.6 percent of individuals will develop bipolar I disorder in their lifetime6.

The FDA approval was based on two multicenter, randomized, double-blind, placebo-controlled clinical trials that evaluated SEROQUEL when used as an adjunct therapy to lithium or valproate in the maintenance treatment of adult patients with bipolar I disorder (n=703, n=623 respectively)7,8. The rigorous study design included a 12 to 36 week stabilization phase which was followed by up to two years of randomized double-blind treatment (mean duration of randomized quetiapine treatment was 189 days7 and 240 days8 respectively).

In both studies, patients with bipolar I disorder whose most recent episode was manic, depressed, or mixed, were treated with either SEROQUEL (flexible dosing between 400 and 800 mg per day in divided doses) plus lithium-or-divalproex or placebo plus lithium-or-divalproex9. The primary endpoint, which was time to recurrence of a depressive, manic, or mixed mood event, compared with placebo, was significant for SEROQUEL compared with placebo in both studies9. Pooled study results indicated that patients treated with SEROQUEL plus lithium-or-divalproex (n=646) had a risk reduction of 70% relative to those treated with placebo plus lithium-or-divalproex (n=680) for time to recurrence of a mood event (HR: 0.30; 95% CI: 0.24, 0.37; p<0.001)9. This reduction in risk was significant for both recurrence of manic episodes (HR: 0.30; 95% CI: 0.22, 0.41; p<0.001) and recurrence of depressive episodes (HR: 0.30; 95% CI: 0.23, 0.40; p<0.001). The proportion of patients who relapsed when treated with SEROQUEL was 19.3% [125/646] versus 50.4% [343/680] of patients on placebo9.

Adverse events in these trials, which were monitored during both the open-label stabilization phase and the randomized controlled-phase, were generally consistent with those reported in short term, placebo-controlled trials for SEROQUEL. In the pooled data of the two clinical studies, a greater incidence of blood glucose increases to hyperglycemic levels ( 126mg/dL) was observed in patients randomized to SEROQUEL plus lithium-or-divalproex than in patients randomized to placebo plus lithium-or-divalproex. The SEROQUEL prescribing information was updated in July 2007 to reflect the increases in blood glucose levels observed in these trials.

About Bipolar Disorder

Approximately eight million American adults are affected by bipolar disorder, a serious psychiatric condition also known as manic depressive illness4,5. Bipolar disorder consists of recurring episodes of mania and depression. Bipolar I disorder is characterized by one or more manic or mixed episodes, often with episodes of major depression, whereas bipolar II disorder is distinguished by one or more major depressive episodes accompanied by at least one hypomanic episode6. In the long term, patients with bipolar I disorder experience depressive symptoms, including prolonged periods of sadness, loss of energy, persistent lethargy, and recurring thoughts of death or suicide - three times longer than manic symptoms10,11. Similarly, patients with bipolar II disorder spend almost forty times longer in the depressed state than in hypomania12. Bipolar disorder is often misdiagnosed as unipolar depression. This misdiagnosis can lead to unfocused treatment that may exacerbate the disease. In fact, many patients face up to ten years without appropriate treatment before a correct diagnosis is made13. Up to 50 percent of patients with bipolar disorder attempt suicide, and approximately 10 to 15 percent complete suicide14. Bipolar Disorder is typically managed through a treatment strategy with several phases - including acute and maintenance phases. In the acute phase, the aim is to improve the acute symptoms of the patient. The maintenance treatment phase aims to prevent the recurrence of the future episodes3,15.

About SEROQUEL and SEROQUEL XR

Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 22 million* patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 79 countries for the treatment of bipolar mania, and in 11 countries including the US for the treatment of bipolar depression. Beside today's announcement of the approval of SEROQUEL by the FDA in the US for the maintenance treatment of patients with bipolar I disorder, as adjunct to lithium or divalproex, a further submission was recently made seeking a similar approval in Europe, in line with previously announced clinical development plans. The European bipolar maintenance submission includes data from a study of SEROQUEL as monotherapy in the maintenance treatment of patients with bipolar I disorder.

SEROQUEL XR™ is approved in the US and 25 further countries for the treatment of schizophrenia in adult patients and for maintenance treatment of schizophrenia in adult patients. It was launched in the US in 2007 and earlier this year AstraZeneca announced the submission of regulatory applications in both the US and European Union for SEROQUEL XR in the treatment of manic episodes associated with bipolar disorder, and the treatment of depressive episodes associated with bipolar disorder. An sNDA for SEROQUEL XR seeking approval for the treatment of Major Depressive Disorder in the US was also announced in February. SEROQUEL XR is not approved for these indications at this time and the applications remain under review by the regulatory authorities.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. In the United States, AstraZeneca is a $13.35 billion dollar healthcare business with 12,200 employees committed to improving people's lives. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.

*Based on assumptions: (1) estimated number of prescriptions per patient based upon IMS APLD data; and (2) IMS Prescription data for SEROQUEL covering 13 major markets in which this data is available since the time of launch.

For more information visit http://www.astrazeneca.com or http://www.astrazeneca-us.com.

References

1.SEROQUEL Prescribing Information. Available here. Accessed April 23, 2008.

2.Data on File, AstraZeneca LP, DA-SER-51.

3.Shastry, BS. Bipolar disorder: an update. Neurochemistry International. 2005; 46:273-279.

4.Hirschfeld RMA, Calabrese JR, Weissman MM, et al. Screening for Bipolar in the Community. J Clin Psychiatry. 2003; 64:53-59.

5.U.S. Bureau of the Census - 2005. Available here. Accessed April 2, 2007.

6. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000: 382-392.

7. Vieta E, Eggens I, Persson I, et al. Efficacy and safety of quetiapine in combination with lithium or divalproex as maintenance treatment for bipolar I disorder [poster]. Presented at: The 20th European College of Neuropsychopharmacology Congress; October 13-17, 2007; Vienna, Austria.

8. Suppes T, Liu S, Paulsson B, et al. Maintenance treatment in Bipolar I disorder with quetiapine concomitant with lithium or divalproex: a North American placebo-controlled, randomized multicenter trial [poster]. Presented at the 46th Annual Meeting of the American College of Neuropsychopharmacology; December 9-13, 2007; Boca Raton, FL, USA.

9. Brecher M, Liu S, Paulsson B. Quetiapine in the maintenance treatment of bipolar I disorder: combined data from two long-term, phase III studies [poster]. Presented at: the 3rd Biennial Conference of the International Society for Bipolar Disorders; January 27-28, 2008; Delhi, India; January 30, 2008; Agra, India.

10. Introduction to Depression and Bipolar Disorder. Available here. Accessed March 12, 2007.

11. Judd LL, Akiskal HS, Schettler PJ, et al. The Long-term Natural History of the Weekly Symptomatic Status of Bipolar I Disorder. Arch Gen Psychiatry. 2002; 59:530-537.

12. Judd LL, Akiskal HS, Schettler PJ, et al. A Prospective Investigation of the Natural History of the Long-term Weekly Symptomatic Status of Bipolar II Disorder. Arch Gen Psychiatry. 2003; 60:26 -269.

13. Hirschfeld RMA, Lewis L, Vornik LA. Perceptions and Impact of Bipolar Disorder: How Far Have We Really Come? Results of the National Depressive and Manic- Depressive Association 2000 Survey of Individuals With Bipolar Disorder. J Clin Psychiatry. 2003; 64:161-174.

14. Oquendo MA, Chaudhury SR, Mann JJ. Pharmacotherapy of Suicidal Behavior in Bipolar Disorder. Archives of Suicide Research. 2005; 9(3):237-250.

15. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Bipolar Disorder, Second Edition. April 2002. See here.

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