Treating Both Poles of Bipolar Disorder: Pivotal Study Confirms Potential of Quetiapine as First Atypical Antipsychotic Monotherapy

For Healthcare and Medical Reporters (non-US and non-UK)

The results of a pivotal study confirm the potential of quetiapine fumarate (SEROQUEL) as a monotherapy (treatment with a single antipsychotic medicine) for acute bipolar depression. Quetiapine is an atypical anti-psychotic and it is already established as an effective treatment for schizophrenia, and the manic phases of bipolar disorder, but it is not approved for bipolar depression.

From the first week of the BOLDER II (BipOLar DEpRession) study, improvements in the severity of depressive symptoms (MADRS total scores*) were significantly greater with quetiapine 300 and 600 mg/d than with placebo (week 1, change from baseline with quetiapine 300 and 600 mg/d: -9.42 and -9.14, respectively; both P<0.001 vs placebo: -6.10) and the improvements continued during the eight week study (week 8, change from baseline with quetiapine 300 and 600 mg/d: -16.94 and -16.00 respectively; both P<0.001 vs placebo: -11.93. In BOLDER II 509 patients were randomized to treatment and 59% completed the

study. (1)

The data support the findings of the previously reported BOLDER I study(2) and together these two studies represent one of the largest placebo-controlled investigations ever conducted for the acute treatment of bipolar depression.

Bipolar disorder affects around 3-4 per cent of the adult population and is characterised by recurring periods of mania and depression.(3) Up to 56 percent of people with bipolar depression attempt suicide and approximately 10 to 15 per cent commit suicide.(4)

In an analysis of the BOLDER I and BOLDER II data (1045 patients)(5) suicidal thoughts (MADRS** item 10 score) decreased significantly more with quetiapine at both doses than with placebo (week 8 scores, 300 mg/d: -0.98; P<0.001; 600 mg/d: -0.92; P=0.001; vs placebo: -0.64).

In a similar analysis of anxiety symptoms scores (6), symptoms improved significantly more in patients treated with quetiapine at both doses compared to placebo (HAM-A total scores*** at week 1, change from baseline, 300 mg/d: -4.59, P<0.001; 600 mg/d: -4.10, P=0.003 vs placebo: -2.77; at week 8, change from baseline, 300 mg/d: -10.12 and 600 mg/d: -10.48; both P<0.001 vs placebo: -6.88)(5).

In addition, a sub-group analysis of bipolar disorder II patients from the BOLDER I and BOLDER II studies found that improvement in severity of depressive symptoms (mean MADRS total score*) from baseline was significantly greater with quetiapine 300 and 600 mg/d than placebo, from the first assessment (Week 1) through Week 8(7).

"Results from BOLDER II are remarkably similar to those found in BOLDER I, the first large-scale study that examined SEROQUEL treatment of depressive episodes in bipolar I and II patients. The replication of BOLDER I by BOLDER II adds considerable strength to the BOLDER data," said Michael E. Thase MD, of the Department of Psychiatry at University of Pittsburgh Medical Center, USA and principal investigator of BOLDER II. "In the past, doctors have typically treated bipolar disorder with both a mood stabilizer and an antidepressant. Having a single medication to treat both the manic and depressive episodes of this condition would be a significant medical advance."

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 said the fact that a study on the scale of BOLDER II replicates the findings of BOLDER I so closely is both remarkable and exciting, offering the hope of similar consistency in the real-world setting.

"As a clinician, when you treat someone with bipolar depression you ask yourself -- what can I do to reduce the chance of this person committing suicide; how can I get symptoms under control to give them a better quality of life; and finally, will they be satisfied with the treatment and continue taking it? The results of the BOLDER study suggest that medical science can help us answer these questions better in the future."

Quetiapine was shown to be well tolerated and the rate of serious adverse events was low and comparable in all treatment groups in both studies. The most common adverse events reported in the trial were constipation, dizziness, dry mouth, sedation and somnolence. In BOLDER II rates of discontinuation due to adverse events (AEs) were 8.1%, 11.2% and 1.2% on the 300mg and 600mg quetiapine treatment arms, and on placebo, respectively (1).

Quetiapine (quetiapine fumarate) has a well-established safety and efficacy profile and to date over 16 million people have been treated with quetiapine worldwide. Quetiapine has been licensed for the treatment of schizophrenia since 1997 and it is available in 85 countries for the treatment of this condition. Quetiapine is also licensed in 73 countries for the treatment of

In December 2005, AstraZeneca submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) to seek approval for a new indication for SEROQUEL(R) for the treatment of patients with depressive episodes associated with bipolar disorder.

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 $23.95 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience,

For further information, please visit http://www.astrazeneca.com or http://www.astrazenecapressoffice.com Further information is also available at the psychiatry resource Internet site http://www.psychiatry-in-practice.com

Notes to Editors:

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-Asberg 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.

** Suicidality was measured using MADRS item 10 ("suicidal thoughts")

and Hamilton Rating Scale for Depression (HAM-D) item 3 ("suicide")

scores.

(HAM-A) scores.

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.

A randomized, double-blind, placebo-controlled trial of quetiapine in

The treatment of bipolar I or II depression. Am J Psychiatry.

2005;162;1351-1360.

bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-59.

A Symptomatic Review of Risk Factors. J Clin Psychiatry.

2005;66:693-704.

efficacy in reducing suicidality in bipolar depression. Poster

presented at the American Psychiatric Association Annual Meeting,

Toronto, 2006.

in bipolar depression with quetiapine monotherapy: results from two

placebo-controlled studies. Presented at the American Psychiatric

Association Annual Meeting, Toronto, 2006.

bipolar II depression: Pooled results from two placebo-controlled

studies. Presented at the American Psychiatric Association Annual

Meeting, Toronto, 2006.

SOURCE: AstraZeneca

CONTACT: James Read,

AstraZeneca,

+1-302-885-9944,

mobile: +1-302-750-7356,

[email protected] , or

Maren Koban of Hill & Knowlton,

+44-207-973-4497,

mobile: +44-7713-631-514,

[email protected]

Web site: http://www.astrazeneca.com

http://www.astrazenecapressoffice.com

http://www.psychiatry-in-practice.com

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