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Statistically Significant Decrease in Depression Scores Demonstrated in Quetiapine Fumarate Bipolar Study

WILMINGTON, Del., July 1 /PRNewswire-FirstCall/ -- AstraZeneca (NYSE: AZN - News) today announced the publication of results from a large-scale clinical study that examined its psychotropic medication SEROQUEL® (quetiapine fumarate) as a treatment for depressive episodes in patients with bipolar I and II disorders. In the study, published in the July issue of the "American Journal of Psychiatry," patients receiving SEROQUEL showed a statistically significant decrease in depression scores(*) at week one and continued to decrease throughout the eight-week study. More than half of the patients receiving SEROQUEL responded(+) and achieved remission. (++,1)

This is the first published large-scale, controlled clinical trial to evaluate SEROQUEL as a monotherapy treatment for depression in outpatients with both bipolar I and bipolar II disorders. SEROQUEL is approved for the treatment of acute manic episodes associated with bipolar I disorder and the treatment of schizophrenia.(2) It is currently under investigation for use in the treatment of bipolar depression.

Bipolar disorder, which affects more than 7 million American adults every year,(3) consists of recurring episodes of mania and depression. "The standard for treating bipolar disorder has not been optimal, with multiple medications required to manage the depressive and manic states," said Joseph Calabrese, M.D., principal investigator and co-director of the National Institute of Mental Health Bipolar Research Center at University Hospitals of Cleveland and Case Western Reserve University. "These data have prompted further studies that, if successful, should make SEROQUEL the first agent approved for the treatment of patients with both depressive and manic episodes associated with bipolar disorder."

Patients with bipolar disorder are symptomatic almost half of their lives, and approximately two-thirds of that time is spent in the depressed phase of the illness.(5) Prolonged periods of sadness, unexplained loss of energy, persistent lethargy and recurring thoughts of death or suicide characterize depressive episodes.(6) Up to 20 percent of patients with bipolar disorder attempt suicide.(1)

The most common adverse events reported in this study were similar to those seen in clinical trials for acute bipolar mania and included: dry mouth (42%), sedation (31%), somnolence (26%), dizziness (20%), constipation (11%), headache (11%) and fatigue (10%).(2) There were no significant differences in the rates of serious adverse events across treatment groups, and no serious adverse events were considered treatment related.

"The results of this study are an exciting step in the exploration of SEROQUEL and the treatment of depressive episodes associated with bipolar disorder," said Wayne Macfadden M.D., U.S. Medical Director for SEROQUEL. "AstraZeneca is dedicated to improving patient's lives and developing new treatments for mental illness."

About the Study
The study results are from a double-blind, placebo-controlled trial of 542 outpatients with bipolar I or II disorder who were randomized to receive eight weeks of treatment with fixed doses of SEROQUEL (300 mg or 600 mg) or placebo administered once daily.(1) Results showed:

  • Patients taking SEROQUEL had a statistically significant decrease in mean MADRS total scores compared to patients taking placebo [mean change in MADRS scores were: (-)16.7 for SEROQUEL 600 mg and (-)16.4 for SEROQUEL 300 mg vs. (-)10.3 for placebo; (p At final assessment, approximately 58 percent of patients treated with either dose of SEROQUEL achieved a response to treatment,(A) compared with 36 percent of patients taking placebo (p The proportion of patients meeting remission criteria(**) was 52.9 percent in both the 600 mg and 300 mg groups taking SEROQUEL, versus 28 percent for placebo at final assessment (p Nine out of ten MADRS items-including sadness, the inability to have feelings, pessimism, and suicidal thinking-had statistically significant reductions in the 600 mg SEROQUEL group. In patients receiving 300 mg of SEROQUEL, a significant reduction was seen in the rating score of eight out of the ten MADRS items (p About Bipolar Disorder
    Bipolar I disorder consists of recurring episodes of mania with or without depression. Bipolar II disorder consists of recurring episodes of hypomania and depression.(7) In the long term, patients with bipolar I disorder spend three times longer in the depressed state than in mania.(1) Patients with bipolar II disorder have traditionally been difficult to treat as they spend almost forty times longer in the depressed state than in mania. Without appropriate treatment, patients usually suffer for a lifetime with periods of wellness and functioning punctuated by severe episodes of illness.(7) Both men and women are equally at risk for this illness, which most often emerges in adolescence or young adulthood and recurs throughout life.(7)

    Important Safety Information
    SEROQUEL is indicated for the treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy with lithium or divalproex, and the treatment of schizophrenia. Patients should be periodically reassessed to determine the need for continued treatment. It is recommended SEROQUEL be taken twice daily in divided doses.

    Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death compared to placebo (4.5% vs. 2.6% respectively). SEROQUEL is not approved for the treatment of patients with dementia-related psychosis.

    Prescribing should be consistent with the need to minimize the risk of tardive dyskinesia. A rare condition referred to as neuroleptic malignant syndrome has been reported with this class of medications, including SEROQUEL.

    Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including SEROQUEL. Patients starting treatment with atypical antipsychotics who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.

    Precautions include the risk of seizures, orthostatic hypotension and cataract development.

    The most commonly observed adverse events associated with the use of SEROQUEL in clinical trials were somnolence, dry mouth, dizziness, constipation, asthenia, abdominal pain, postural hypotension, pharyngitis, SGPT increase, dyspepsia, and weight gain.

    For full prescribing information for SEROQUEL, please visit the website https://www.seroquelxr.com/.

    * Depression scores were measured by the Montgomery-Asberg Depression Rating Scale (MADRS).(1) The MADRS scale measures the severity of a number of depressive symptoms including mood and sadness, tension, sleep, appetite, energy, concentration, suicidal ideation and restlessness.(4) The MADRS score decreases as depressive symptoms improve. In this study, mean change in MADRS scores were (-)16.7 for SEROQUEL 600 mg and (-)16.4 for SEROQUEL 300 mg vs. (-)10.3 for placebo; (p + SEROQUEL patients met response criteria (58.2% in the 600 mg group and 57.6% in the 300 mg group) versus 36.1% for placebo.(1)
    ++ 52.9% of SEROQUEL patients met remission criteria versus 28.4% in those taking placebo.(1)
    (A) Response defined as a decrease of at least 50% in MADRS score from baseline.
    ** Remission defined as MADRS score of 12 or lower.

    References
    (1) 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, July 2005.
    (2) SEROQUEL® (quetiapine fumarate) Prescribing Information, Rev 07/04, AstraZeneca Pharmaceuticals LP, Wilmington, Delaware.
    (3) Hirschfeld et al. Screening for Bipolar in the Community. J Clin Psychiatry, 64:1, January 2003.
    (4) Lundbeck Institute. Psychiatric Rating Scales. PDF available at: http://www.brainexplorer.org/factsheets/Psychiatry%20Rating%20Scales.pdf. Accessed June 16, 2005.
    (5) 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
    (6) Introduction to Depression and Bipolar Disorder. Depression and Bipolar Support Alliance, 730 N. Franklin Street, Suite 501, Chicago, Illinois 60610-7224. Available at: http://www.dbsalliance.org/PDF/IntroBrochureC2.pdf Accessed December 13, 2004.
    (7) Kramlinger K. Mayo Clinic on Depression. Rochester, Minn.: Mayo Clinic Health Information, 2001.

    Source: AstraZeneca

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