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

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

May 24, 2006

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

    TORONTO, May 24 /Xinhua-PRNewswire/ -- 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 per cent 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 mania
associated with bipolar disorder. SEROQUEL(R) (quetiapine)
is marketed by AstraZeneca and it is the number one
prescribed atypical antipsychotic in the United States,
with global sales of $2.8 billion in 2005.

    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,
respiratory, oncology and infection products. AstraZeneca
is listed in the Dow Jones Sustainability Index (Global) as
well as the FTSE4Good Index.

    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.

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

    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) Calabrese JR, Keck PE, Macfadden W, et al, for the
BOLDER Study Group. 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.

    (3) Hirschfeld RMA, Calabrese JR, Weissman MM, et al.
Screening for bipolar disorder in the community. J Clin
Psychiatry. 2003;64:53-59.

    (4) Hawton, et al. Suicide and Attempted Suicide in
Bipolar Disorder: A Symptomatic Review of Risk Factors. J
Clin Psychiatry. 2005;66:693-704.

    (5) Macfadden W, Minkwitz, Spong E. Quetiapine
monotherapy demonstrate efficacy in reducing suicidality in
bipolar depression. Poster presented at the American
Psychiatric Association Annual Meeting, Toronto, 2006.

    (6) Lydiard BR, Raines S, Macfadden W. Improvement in
anxiety symptoms in bipolar depression with quetiapine
monotherapy: results from two placebo-controlled studies.
Presented at the American Psychiatric Association Annual
Meeting, Toronto, 2006.

    (7) Hirschfeld RM, Suppes T, Vieta E et al. Quetiapine
monotherapy for bipolar II depression: Pooled results from
two placebo-controlled studies. Presented at the American
Psychiatric Association Annual Meeting, Toronto, 2006.

    For more information, please contact:

     James Read, 
     AstraZeneca
     Tel:    [phone]
     Mobile: [phone] 
     Email:  [e-mail]

     Maren Koban 
     Hill & Knowlton
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]

SOURCE  AstraZeneca