AstraZeneca announced that the US FDA has approved additional efficacy labelling information, based on 12-week data for Seroquel (quetiapine), a psychotropic medication indicated for the treatment of acute manic episodes associated with bipolar I disorder.

Seroquel is the first medication in its class to include monotherapy safety and efficacy data for acute manic episodes associated with bipolar disorder extending beyond three weeks in its label. These latest data demonstrate that Seroquel treatment alone works early and continues to work through 12 weeks, company said in a release.

The data, part of the large scale effort to examine Seroquel's use in bipolar disorder, showed that after 12 weeks, approximately two-thirds of patients receiving Seroquel alone experienced significant improvement in manic symptoms and achieved remission. (Remission defined as a score of less than 12 on the Young Mania Rating Scale). Seroquel is not only effective in reducing symptoms of acute mania the first few weeks, but is also effective in the subsequent 'continuation phase', when patients can continue to have significant symptoms and are still at risk of relapsing, says the release.

The new label information is supported by data from two, 12-week, double-blind, randomised, placebo-controlled trials assessing the safety and efficacy of Seroquel monotherapy for the treatment of manic episodes in a large cohort of adults with bipolar I disorder. A total of 599 patients experiencing a manic episode were assigned to receive Seroquel (from 200 mg/day up to 800 mg/day), placebo, or an active control (lithium or haloperidol). The primary endpoint was change from baseline YMRS (Young Mania Rate Scales) total score at day 21 of treatment (week three); secondary endpoints included change from baseline YMRS total score at day 84 (week 12).

The combined analysis of two 12-week, monotherapy, double-blind, placebo-controlled trials showed that- after 12 weeks, 66.8 per cent of Seroquel-treated patients achieved a response (defined as greater than or equal to 50 percent decrease from baseline YMRS score) versus 40.0 percent of the placebo group (p<0.001).

After 12 weeks, 65.4 per cent of Seroquel-treated patients achieved remission (defined as YMRS less than or equal to 12), versus 35.9 percent with placebo (p<0.001). Improvement in manic symptoms based on change in YMRS score in patients treated with Seroquel was significantly greater than placebo-treated patients, as early as day four onwards (p=0.02).

Bipolar disorder is a serious mental illness that affects almost 4 percent of the adult population and is the sixth leading cause of disability in the world. More than half of those with bipolar disorder stop taking their medication at some point during their illness, subjecting themselves to a high risk of relapse and an increased risk of suicide. A medication's overall efficacy and tolerability profile is therefore vital to helping patients comply with their medication.

Seroquel was originally approved by the FDA in January 2004 as a monotherapy and adjunct therapy with lithium or divalproex, for the short-term treatment of acute manic episodes associated with bipolar I disorder. This approval was based on efficacy results following three weeks of treatment. These trials showed Seroquel to be well-tolerated and effective in the treatment of manic episodes - excited mental states seen in bipolar disorder that are characterized by impulsive behaviour, racing thoughts, pressured speech, and decreased need for sleep.

AstraZeneca also announced data showing that Seroquel may be an effective option for the treatment of agitation associated with dementia, including Alzheimer's disease, in the elderly patient population.

The results, presented at the 9th International Conference on Alzheimer's Disease and Related Disorders in Philadelphia, show that elderly patients with dementia who were treated with Seroquel, experienced improvement in symptoms of agitation. Additionally, patients treated with Seroquel showed no cerebrovascular adverse events (CVAEs), which have been associated with the use of some other atypical antipsychotics in this patient population.

The STAR trial, a 10-week, multicentred, double-blind, fixed-dose, 3-arm, placebo-controlled trial, randomised 333 institutionalised patients (mean age 83 years) to receive Seroquel 200mg/day, Seroquel 100mg/day or placebo. The key efficacy measures were the Positive and Negative Syndrome Scale-Excitement Component (PANSS-EC) and Clinicians' Global Impression of Change (CGI-C) scales. These efficacy measures were analysed in the Intent to Treat (ITT) and Per Protocol (PP) populations using the Last Observation Carried Forward (LOCF) and Observed Case (OC) methods.

Additional results presented at the Conference, from two pooled, placebo-controlled, 10-week trials, also support the CVAE findings of the STAR trial. 684 patients (mean age 83 years) were randomised to receive Seroquel, haloperidol, or placebo. The analysis found that elderly patients receiving Seroquel were not at an increased risk of CVAEs, such as stroke or transient ischaemic attacks (TIAs), as demonstrated by the following results: