Role For Seroquel In The Treatment Of Bipolar Depression

Main Category: Bipolar
Article Date: 08 Jul 2005 - 11:00 PDT

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Published data shows Seroquel is efficacious in treating core symptoms of bipolar depression, including the reduction of suicidal thoughts -

It is estimated that 25% to 50% of people with bipolar, a severe mood disorder, attempt suicide at least once[i]. Significant new data published this month show that Seroquel (quetiapine) is approximately twice as effective as placebo at reducing suicidal thoughts in patients with bipolar depression*, as early as one week after treatment.[ii]

Seroquel is not licensed for bipolar depression. Seroquel is licensed for the treatment of manic episodes associated with bipolar disorder and for the treatment of schizophrenia.[iii]

The BOLDER (BipOLar DepRession) eight week, multi-centered, randomised, double-blind placebo-controlled study is thought to be the first published large-scale, controlled study to assess the efficacy of any pharmacological treatment in patients with bipolar I and bipolar II depression.2 The study demonstrated that Seroquel significantly improved core symptoms of depression and anxiety improving 9 out of 10 MADRS* items compared to placebo, these include apparent sadness, inability to feel, pessimistic thoughts and suicidal thoughts. In addition, Seroquel improved quality of sleep and quality of life significantly compared to placebo and was found to be well tolerated.2

"There are at present few adequate treatments available for bipolar depression, so patients and their clinicians struggle with this disabling condition. Current UK guidelines suggest the use of antidepressants for bipolar depression, which seems the obvious solution, but this carries a risk of switching into a manic state and destabilisation over time. The benefits from mood stabilisers in the short term are variable. The results of this research, thus, make an important contribution to finding an effective, fast-acting treatment with few troublesome side effects" commented Professor Tony Hale, head of the Division of Psychiatry at the University of Kent.

"Bipolar patients spend a third of their lives depressed, and the vast majority of bipolars who commit suicide do so when they are depressed[iv]. This study shows reduction in suicidal thoughts and other depressive symptoms, with both doses of Seroquel, within the first week of treatment. It is particularly impressive that 53% of patients taking Seroquel achieved remission, the gold-standard for improvement, within the 8 weeks of the study. The treatment was very well tolerated by patients", concluded Professor Hale.

Reduction of suicidal thoughts is an important factor in the treatment of bipolar depression. New research from the British Journal of Psychiatry[v] suggests that suicidal thoughts are directly linked to the act of committing suicide. Helping to prevent patients from thinking suicidal thoughts rather than focusing on the means of suicide may provide a new approach to this distressing event. The authors of a second recent study[vi] investigating trends in suicide call for continued efforts to identify untreated individuals with suicidal ideation before the occurrence of attempts and to improve treatment effectiveness.

Professor Joseph Calabrese, lead investigator of the BOLDER study and Co-Director of the Bipolar Research Centre at University Hospitals of Cleveland said, "Until now, the standard for treating bipolar disorder has not been optimal, with multiple medications required to manage the depressive and manic states," said Professor Joseph Calabrese, MD, Co-Director of the National Institute of Mental Health Bipolar Research Center at University Hospitals of Cleveland and Case Western Reserve University, and BOLDER study author.

Bipolar I disorder is a severe mood disorder where patients swing between states of depression (low mood and energy) and mania (heightened, elevated, ecstatic mood and energy). Bipolar II disorder is a variant whereby patients alternate between intense depression and a milder manic state known as 'hypomania'. Patients with both types of bipolar disorder spend significantly longer depressed than manic or hypomanic[vii], and yet historically the treatment of the depressive phase has not been well studied. [viii]

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 over $21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology and neuroscience products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index.

In Neuroscience, AstraZeneca is dedicated to providing medicines that have the potential to change patients' lives. The company already markets several products including Seroquel, one of the fastest growing global antipsychotics with proven efficacy and a very favourable side effect profile; and Zomig, a reliable migraine therapy and a leader within the triptan market. The Neuroscience pipeline includes leading approaches for the treatment of depression and anxiety, overactive bladder, dementia and stroke, pain control and anaesthesia.

Seroquel is a trademark of the AstraZeneca group of companies.

Seroquel has been licensed for the treatment of schizophrenia since 1997 and is available in 82 countries for the treatment of this condition. Seroquel is also licensed in 63 countries for the treatment of mania associated with bipolar disorder, including the US, Canada and several European countries. To date, over 8 million people have been treated with Seroquel worldwide.

Abstract:

A Randomized, Double-Blind, Placebo-Controlled Trial of Quetiapine in the Treatment of Bipolar I or II Depression

Joseph R. Calabrese, M.D. Paul E. Keck, Jr., M.D. Wayne Macfadden, M.D.
Margaret Minkwitz, Ph.D. Terence A. Ketter, M.D. Richard H. Weisler, M.D.
Andrew J. Cutler, M.D. Robin McCoy, R.N. Ellis Wilson, M.S. Jamie Mullen, M.D.

The BOLDER Study Group

Objective: There is a major unmet need for effective options in the treatment of bipolar depression.

Method: Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Åsberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire.

Results: Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Åsberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (≥50% Montgomery-Åsberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery- Åsberg Depression Rating Scale ≤12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Åsberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively).

Conclusions: Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.

(Am J Psychiatry 2005; 162:1351-1360)

* As measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety (HAM-A)

[i] Jamison KR. Suicide and bipolar disorder. J Clin Psychiatry 2005; 46(4): 273-9

[ii] Calabrese et al. Am J Psychiatry, 2005; 162(6) 1351-1360

[iii] Seroquel Summary Product Characteristics. November 2003.

[iv] Isometsa E et al. Suicide in psychotic major depression. J Affect Disord 1994 31(3): 187-91

[v] Harris L, Hawton K & Zahl D. Value of measuring suicidal intent in the assessment of people attending hospital following self-poisoning or self-injury. British Journal of Psychiatry, 2005; 186: 60-66.

[vi] Kessler et al. Trends in suicide ideation, plans, gestures and attempts in the United States 1990-1992 to 2001-2003. JAMA, 2005; 293(20): 2487-2495.

[vii] Judd LL, Akiskal HS, Schettler PJ et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003;60:261-269.

[viii] Keck PE Jr, Nelson EB, McElroy SL. Advances in the pharmacologic treatment of bipolar depression. Biol Psychiatry 2003;53:671-679.

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