New Data Presented For SEROQUEL XRTM In Major Depressive Disorder And Generalised Anxiety Disorder

Main Category: Depression
Also Included In: Psychology / Psychiatry
Article Date: 13 Nov 2008 - 1:00 PDT

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Two studies presented today at the 8th International Forum on Mood and Anxiety Disorders (IFMAD) in Vienna demonstrated that once-daily SEROQUEL XRTM (quetiapine fumarate extended release tablets) provided significant symptom relief for elderly patients (>65 years of age) with major depressive disorder (MDD) and generalised anxiety disorder (GAD). In both 9-week monotherapy studies - one in MDD (Sapphire)1 and the other in GAD (Chromium)2 - symptoms had improved significantly within one week of quetiapine XR treatment. Further new quetiapine XR data presented at IFMAD included an analysis of patients with anxious depression3 and results from the Amber study4 in MDD.

"Major depressive disorder and generalised anxiety disorder are two closely related conditions that can be difficult to treat, particularly in elderly people," said Professor Stuart Montgomery, Imperial College School of Medicine, London. "In these two studies with elderly patients, quetiapine XR worked quickly to relieve depression and anxiety symptoms within a week, and symptoms continued to improve until the end of the studies. These results are consistent with the positive results previously reported from other studies conducted with quetiapine XR in MDD and GAD in non-elderly adults."

The Sapphire (Study 14) and Chromium (Study 15) studies were double-blind, placebo-controlled trials that randomised elderly patients to receive flexible dose quetiapine XR monotherapy (50-300 mg/day) or placebo. The Sapphire study included 388 elderly MDD patients with a mean age of 71.3 years. After 9 weeks of treatment with quetiapine XR (mean dose 159.9 mg/day), Montgomery-Åsberg Depression Rating Scale (MADRS) total scores were significantly reduced compared with placebo (-16.33 vs. -8.79; P<0.001), and this difference was significant as early as week 1 (-4.65 vs. -2.56, P<0.001).1 Other secondary endpoints, including response and remission rates and health-related quality of life were also significantly improved at week 9 (P<0.001).

The Chromium study2 included 450 elderly patients (mean age 70.4 years) with GAD. Patients who received quetiapine XR (mean dose 167.6 mg/day) had a significantly greater reduction in Hamilton anxiety scale (HAM-A) scores from baseline compared with placebo (-14.97 vs. -7.21; P<0.001) after 9 weeks of treatment. The improvement was evident at week 1 (-4.18 for quetiapine XR vs. -2.35 for placebo; P<0.001). Quetiapine XR treatment also led to significant improvements in other secondary endpoints including HAM-A response and remission rates, MADRS total score and health-related quality of life compared with placebo at week 9 (P<0.001).

Safety and tolerability findings were consistent with the known safety profile of quetiapine. The most common adverse events with quetiapine XR were somnolence, dry mouth, dizziness, and headache.

Other quetiapine XR studies presented at IFMAD include a subgroup analysis of pooled results from two similar randomised, double-blind, placebo-controlled trials (studies 1 and 25,6) examining 788 adults defined as having MDD and high levels of anxiety (anxious depression) at entry to the studies.3 Anxious depression has been reported to be associated with poor rates of remission and response to antidepressants compared with nonanxious depression.7 In patients with anxious depression, quetiapine XR monotherapy significantly reduced MADRS total scores at study end for both 150 mg (-14.8; P<0.001) and 300 mg (-15.1; P<0.001) doses compared with placebo (-11.5), with MADRS total score improvements demonstrated as early as Week 1 (P<0.001).

Finally, the Amber study (Study 4)4 was a double-blind, active- and placebo-controlled study that randomised patients to quetiapine XR 150 mg/day, escitalopram 10 mg/day or placebo. After 2 weeks patients were assessed for response (≥20% improvement in MADRS). Patients with adequate response remained on their initial randomised dose, while patients with inadequate response had their dose doubled. MADRS total scores were improved with both quetiapine XR (-17.21) and escitalopram (-16.73), although these improvements were not significantly different from placebo (-15.61). A possible reason for this finding was an unexpectedly high response in the placebo group. It is estimated that approximately half of all clinical studies in MDD fail to reach their primary endpoint.8 Of the eight studies included in the quetiapine XR MDD programme, the Amber study is the only study which failed to demonstrate significant improvement in active treatment compared with placebo.

About MDD and GAD

MDD is characterised by persistent depressive symptoms without a history of manic or hypomanic episodes. Psychological symptoms include guilt, hopelessness, anxiety and suicidal ideation which typically last weeks, months or years,9 while physical symptoms include sleep disturbances, fatigue and weariness, pain, sexual dysfunction and appetite changes.10 The lifetime prevalence of MDD can be as high as 13%.11

GAD is a syndrome of ongoing anxiety and worry that is typically recognised as excessive or inappropriate and lasts for at least 6 months. People with GAD are usually overly concerned about everyday matters and tend to anticipate disaster. Physical symptoms of the disorder include fatigue, headaches, muscle tension, muscle aches, difficulty swallowing, trembling, irritability, sleep disturbances, sweating and hot flushes.12 During their lifetimes, it is estimated that 5.4% of people in Europe will suffer from GAD.13

About SEROQUEL and SEROQUEL XR

A filing for SEROQUEL XR (quetiapine fumarate extended release tablets) seeking approval for the treatment of major depressive disorder (MDD) was made in the US in February 2008 with the EU filing in June. In October this year, SEROQUEL XR became the first atypical antipsychotic to be filed with the EMEA in Europe seeking approval for the treatment of generalised anxiety dsorder (GAD). A similar filing was made to the FDA in May 2008. SEROQUEL XR is not approved for these indications at this time and the applications remain under review by the regulatory authorities.

SEROQUEL XR has been approved in 43 countries for schizophrenia (including all 17 countries in the Mutual Recognition Procedure), 12 countries for bipolar mania, in 7 countries for bipolar depression, in 3 markets for bipolar maintenance, in 1 market for MDD, and in 1 market for GAD. SEROQUEL XR is presented as tablets delivering a dose of 50 mg, 150 mg, 200 mg, 300 mg, or 400 mg of quetiapine free-base.

Launched in 1997, it is estimated that SEROQUEL has been prescribed to more than 22 million patients worldwide*. It is approved in 92 countries for the treatment of schizophrenia, in 88 countries for the treatment of bipolar mania, and in 30 countries including the US for the treatment of bipolar depression.

*Estimates based on IMS APLD and Prescription data.

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References

1. Katila H, et al. Efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD). Presented at the 8th International Forum on Mood and Anxiety Disorders, Vienna, Austria, 12-14 November, 2008.

2. Eriksson H, et al. Double-blind, randomised study of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with generalized anxiety disorder (GAD). Presented at the 8th International Forum on Mood and Anxiety Disorders, Vienna, Austria, 12-14 November, 2008.

3. Demyttenaere K, et al. Once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in major depressive disorder (MDD): analysis in a subgroup of patients with anxious depression. Presented at the 8th International Forum on Mood and Anxiety Disorders, Vienna, Austria, 12-14 November, 2008.

4. Earley W, et al. Double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Presented at the 8th International Forum on Mood and Anxiety Disorders, Vienna, Austria, 12-14 November, 2008.

5. Weisler R, et al. Extended release quetiapine fumarate (quetiapine XR) monotherapy for major depressive disorder (MDD): a double-blind, placebo-controlled study. Presented at the American Psychiatric Association Annual Meeting, Washington, DC, 3-8 May, 2008.

6. Montgomery S, et al. A randomised, placebo-controlled study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Presented at the International Forum on Mood and Anxiety Disorders, Budapest, Hungary, 5-7 December, 2007.

7. Fava M, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008;165:342-51.

8. Mann JJ. The medical management of depression. N Engl J Med 2005;353(17):1819 - 34. 9. Fava M. Somatic symptoms, depression, and antidepressant treatment. J Clin Psychiatry 2002;63(4):305-7.

10. Hasin DS, et al. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62(10):1097-106.

11. National Institute of Mental Health: Anxiety Disorders. NIH Publication No. 06-3879. Available at: http://www.nimh.nih.gov/health/publications/anxiety-disorders/generalized-anxiety-disorder-gad.shtml Accessed 10 October, 2008.

12. Wyrwich KW, et al. A review of the humanistic and economic outcomes in European patients diagnosed with generalized anxiety disorder. Presented at the 161st Annual Meeting of the American Psychiatric Association, Washington, D.C., May 2008. Poster presentation NR3-065.

13. Turner EH, et al. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252 - 60.

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