Source: Urology  |  Posted 5 years ago

ALDERLEY PARK, MACCLESFIELD -- November 17, 2006 -- Results from the newly published BOLDER II (BipOLar DEpRession) study confirm that Seroquel? (quetiapine fumarate) has the potential as a single medication to treat for major depressive episodes in patients with bipolar disorder.

The results, published in the December issue of the Journal of Clinical Psychopharmacology, reinforce the positive findings of the landmark BOLDER I study, and have led the FDA to approve Seroquel for the treatment of depressive episodes associated with bipolar disorder for patients in the US. This means that Seroquel is the first and only single medication approved by the FDA to treat both depressive and manic episodes associated with bipolar disorder.

BOLDER II, an 8-week, multicentre, placebo-controlled trial, found that patients treated with Seroquel 300 mg or 600 mg per day had significant improvements in their depression compared with placebo recipients (P <-.001) as measured by the Montgomery-?sberg Depression Rating Scale (MADRS).1

"Patients treated with Seroquel in BOLDER II saw an improvement in their depressive symptoms within one week and more than half by week eight," said Professor Michael Thase, Medical Director, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, and the study's principal investigator.

A wide range of patients participated in BOLDER II, including those with rapidly cycling disease and those with bipolar I and bipolar II disorders. Significant improvements in MADRS* scores compared to placebo were seen for each of these groups compared with placebo. The exploratory analysis demonstrated significant improvements for Seroquel recipients in secondary measures, including Hamilton Rating Scales for depression (HAM-D)** and anxiety (HAM-A)***, and quality of life scores as measured by the Q-LES-Q**** instrument.

Seroquel was well tolerated in the study and the few serious adverse events that occurred were not considered related to treatment. Dry mouth, sedation, somnolence and dizziness and constipation were the most common adverse events. Among patients treated with Seroquel, the incidence of treatment-emergent mania and extra-pyramidal symptoms were low. Results from BOLDER II confirm earlier findings from BOLDER I, which was published in 2005 and was the first study to report the potential for Seroquel monotherapy in acute bipolar depression1.

As a result of the positive findings from the two BOLDER studies, Seroquel is now the first and only single medication approved by the FDA to treat both the depressive and manic episodes associated with bipolar disorder. "I think this is good news for patients with bipolar disorder, because we know that it's much more difficult to treat depressive episodes than manic episodes," said Professor Thase. "Depressive episodes are far more debilitating for patients and can last three times longer than manic episodes. Now both can be controlled with a single daily treatment that should be easy for patients to use."

Approximately 3?4% of adults worldwide are affected by bipolar disorder, a serious psychiatric condition which was previously known as manic depressive illness2. Bipolar disorder is characterized by recurrent episodes of mania and, more commonly, depression. The disease is chronic and can create considerable problems for patients, spouses and family members if left untreated.

Beyond schizophrenia, bipolar mania and bipolar depression, the ongoing clinical development programme includes investigations of the use of Seroquel in bipolar maintenance. Regulatory filings for the treatment of schizophrenia with a sustained release formulation of quetiapine fumarate, Seroquel SR?, were submitted this year to regulatory authorities in the US, EU and other markets. Ongoing Seroquel SR? clinical studies also cover major depressive disorder and generalized anxiety disorder. Seroquel is the number 1 prescribed atypical antipsychotic in the United States. With a well-established safety and efficacy profile, Seroquel has had more than 19 million patient exposures worldwide since its launch in 1997. In 2005, global sales for Seroquel reached $2.8 billion.

BOLDER I & BOLDER II are both eight week, multi-centre, double-blind placebo-controlled studies. Outpatients with both bipolar I and II disorder were randomised to receive eight weeks' treatment with 300mg or 600mg Seroquel or placebo, administered once daily.

* Depression scores were measured by the Montgomery-?sberg Depression Rating Scale (MADRS), which 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.

** Hamilton Depression Rating (HAM-D) Scale: This scale is used to assess the severity of depression in patients already diagnosed with an affective disorder. The HAM-D score decreases as depressive symptoms improve.

*** Anxiety was measured using the Hamilton Rating Scale for Anxiety (HAM-A) scores.

**** Quality of Life as measured by changes in the mean Quality of Life Enjoyment Satisfaction Questionnaire score (Q-LES-Q).

REFERENCES:
1. Thase M, McCoy R, Chang W, Macfadden W. Efficacy of quetiapine monotherapy in bipolar depression: a confirmatory double-blind, placebo controlled study (the BOLDER II Study). Presented at the American Psychiatric Association Annual Meeting, Toronto, 2006.
2. Hirschfeld RMA, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.

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