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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
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 Centre, 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
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
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 www.astrazeneca.com or
www.astrazenecapressoffice.com. Further information is also available
at the psychiatry resource internet site
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
* 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
** Suicidality was measured using MADRS item 10 ("suicidal
thoughts") and Hamilton Rating Scale for Depression (HAM-D) item 3
*** Anxiety was measured using the Hamilton Rating Scale for
Anxiety (HAM-A) scores.
 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.
 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.
 Hirschfeld RMA, Calabrese JR, Weissman MM, et al. Screening
for bipolar disorder in the community. J Clin Psychiatry.
 Hawton, et al. Suicide and Attempted Suicide in Bipolar
Disorder: A Symptomatic Review of Risk Factors. J Clin Psychiatry.
 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.
 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.
 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.
ots Originaltext: AstraZeneca
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