An analysis of two studies presented today at the 156th annual meeting of the American Psychiatric Association (APA) examined the use of Seroquel as a monotherapy for acute mania in patients suffering from bipolar disorder. Pooled results from two 12-week clinical trials involving more than 600 patients showed that 48.1 per cent of patients treated with Seroquel achieved a response [defined as >50 per cent decrease from baseline YMRS (Young Mania Rating Scale) score], compared with 31.3 per cent of those given placebo.
The data presented are among the first to evaluate the efficacy, tolerability and safety of Seroquel as a monotherapy treatment for acute mania associated with bipolar disorder. The studies presented are from two of three Phase III trials that supported AstraZeneca's Supplemental New Drug Application (sNDA) for Seroquel, in the adjunctive and monotherapy treatment of acute mania associated with bipolar disorder. The sNDA for Seroquel was submitted to the U.S. Food & Drug Administration in December 2002. Seroquel is currently indicated for the treatment of schizophrenia in adults.
"These studies present a fair evaluation of the ability of Seroquel to manage the symptoms of acute mania in patients with bipolar disorder," said Dr. Eduard Vieta, MD, PhD, Clinical Institute of Psychiatry and Psychology, Director of Bipolar Disorders Program, University of Barcelona.
Bipolar disorder, which affects about 2.3 million American adults every year, consists of recurring cycles of mania and depression. It is the second leading cause of neuropsychiatric disability in the world. Both men and women are equally at risk for this illness, which most often emerges in adolescence or young adulthood and recurs intermittently throughout life. More than half of those with bipolar disorder stop taking their medication at some point during their lives, subjecting them to a high risk of a relapse of symptoms and an increased risk of suicide.
A pooled analysis of data from two 12-week, double-blind, randomized, placebo-controlled trials assessed the efficacy and safety of Seroquel monotherapy for the treatment of acute mania in a large cohort of adults with bipolar I disorder. A total of 604 patients experiencing a manic episode were assigned to receive Seroquel (up to 800 mg/day), placebo, lithium or haloperidol, with lithium or haloperidol serving as controls to assess assay sensitivity. The primary endpoint was change from baseline YMRS (Young Mania Rating Scale) total score at day 21 of treatment.1
After three weeks of treatment, patients treated with Seroquel had a YMRS score of -13.58 from baseline, compared to the placebo group's score of -7.76 (p<0.0001) This change began as early as the fourth day of treatment (p=0.021) and continued to increase through day 84 (p<0.0001).
After three weeks, 48.1 per cent of Seroquel-treated patients achieved a response (defined as >50% decrease from baseline YMRS score) versus 31.3 per cent of the placebo group (p=0.0006). 60.8 per cent of patients receiving Seroquel completed the trial whereas only 38.9 per cent receiving placebo completed the trial.
Patients who responded to Seroquel were receiving an average dose of 575.5 mg/day by their third week of treatment. Common adverse events in patients taking Seroquel included insomnia, dry mouth and somnolence.
"These results and other emerging data affirm the progress and focus of several of our clinical trial programs, in which we have examined the ability of Seroquel to control acute manic episodes in patients with bipolar disorder," said Jamie Mullen, MD, Director of Clinical Research, AstraZeneca. "AstraZeneca has a clear commitment to the development of new treatments for mental illness, and is proud of how successful Seroquel has been in treating patients with schizophrenia, since its launch in 1997."
The efficacy and atypical profile of Seroquel is supported by several placebo- and comparator-controlled Phase II and Phase III clinical trials in patients with schizophrenia. In clinical trials, efficacy was demonstrated in a dose range of 150mg/day to 750mg/day. An initial target dose range of 300-400mg can be given in two divided doses daily. In studies supporting the approval of Seroquel (quetiapine fumarate) Tablets, there were no differences from placebo across the clinical dose range in the incidence of EPS, including rigidity and difficulty starting and stopping movement, or in elevation of serum prolactin levels. In addition, studies have shown that Seroquel exhibits a low incidence of hormonal, reproductive system (sexual dysfunction), and anticholinergic side effects (dry mouth, constipation).
The labeling for Seroquel (quetiapine fumarate) Tablets includes a warning relative to a condition known as tardive dyskinesia (which is often associated with long-term use of antipsychotic agents) and a rare condition known as neuroleptic malignant syndrome (NMS symptoms include muscle rigidity, fever, and irregular pulse). Labeled precautions include orthostatic hypotension and the possible risk of cataract development. As with other antipsychotics, therapy with Seroquel should be used cautiously in patients with a history of seizures or with conditions that can potentially lower the seizure threshold. The most common adverse events associated with the use of Seroquel are dizziness (10 per cent), postural hypotension (7 per cent), dry mouth (7 per cent), and dyspepsia (6 per cent), and the majority of events are rated mild or moderate. The safety and effectiveness of Seroquel in pediatric patients have not been established.
Since its approval in September 1997, there have been approximately 14.3 million prescriptions written for Seroquel, or more than 3.5 million patients in the United States.