FDA Approves Seroquel For Maintenance Treatment In Bipolar Disorder
AstraZeneca announced FDA has approved SEROQUEL (quetiapine fumarate tablets) for the maintenance treatment of patients with bipolar I disorder, as adjunct therapy to lithium or divalproex. SEROQUEL is approved by the FDA for the treatment of schizophrenia, and is also the only single agent approved by the FDA for the treatment of both depressive episodes in bipolar disorder and acute manic episodes associated with bipolar I disorder.
Considered one of the most severe forms of mental illness, bipolar disorder currently affects about 8 million adults in the U.S. Bipolar I disorder is a lifelong psychiatric condition characterized by manic or mixed mood episodes, interspersed with major depressive episodes. It is estimated that 0.4 percent to 1.6 percent of individuals will develop bipolar I disorder in their lifetime.
"This new indication for SEROQUEL marks an important milestone in the treatment of bipolar I disorder because it provides patients with another option over the long-term. In fact, despite the number of currently available treatments, many patients with bipolar I disorder do not receive effective therapy and some 20 to 30 percent of patients continue to display residual mood symptoms of bipolar I disorder," said Mark Scott, Executive Director, Clinical Development, SEROQUEL. "The studies showed that SEROQUEL, with lithium or divalproex, can provide clinicians with a safe and effective long-term treatment option that reduced the risk of relapse of both manic and depressive mood events in bipolar I disorder."
The FDA approval was based on two multicenter, randomized, double-blind, placebo-controlled clinical trials that evaluated SEROQUEL when used as an adjunct therapy to lithium or divalproex in the maintenance treatment of adult patients with bipolar I disorder (n=703, n=623 respectively). The rigorous study design included a 12 to 36 week stabilization phase which was followed by a longer-term, randomized, double-blind treatment phase that had a mean duration of exposure of 213.2 days for SEROQUEL and 152.4 days for placebo.
In both studies, patients with bipolar I disorder whose most recent episode was manic, depressed, or mixed, were treated with either SEROQUEL (flexible dosing between 400 and 800 mg per day in divided doses) plus lithium-or-divalproex or placebo plus lithium-or-divalproex. The primary endpoint, which was time to recurrence of a depressive, manic, or mixed mood event, was significant for SEROQUEL compared with placebo in both studies. Pooled study results indicated that patients treated with SEROQUEL plus lithium-or-divalproex (n=646) had a risk reduction of 70% relative to those treated with placebo plus lithium-or-divalproex (n=680) for time to recurrence of a mood event (HR: 0.30; 95% CI: 0.24, 0.37; p<0.001). This reduction in risk was significant for both recurrence of manic episodes (HR: 0.30; 95% CI: 0.22, 0.41; p less than 0.001) and recurrence of depressive episodes (HR: 0.30; 95% CI: 0.23, 0.40; p less than 0.001). The proportion of patients who relapsed when treated with SEROQUEL was 19.3% [125/646] versus 50.4% [343/680] of patients on placebo.
Adverse events in these trials, which were monitored during both the open-label stabilization phase and the randomized controlled-phase, were generally consistent with those reported in short term, placebo-controlled trials for SEROQUEL. In the pooled data of the two clinical studies, a greater incidence of blood glucose increases to hyperglycemic levels (Greater Than or Equal to 126mg/dL) was observed in patients randomized to SEROQUEL plus lithium-or-divalproex than in patients randomized to placebo plus lithium-or-divalproex. The SEROQUEL prescribing information was updated in July 2007 to reflect the increases in blood glucose levels observed in these trials.
"To date, long-term controlled studies of maintenance therapies have been relatively few and typically focused on either the manic or depressive phase of the illness, but not on both," said Mark Scott, Executive Director, Clinical Development, SEROQUEL. "SEROQUEL is the only single agent to offer proven efficacy in both the manic and depressive episodes in bipolar disorder, and now has demonstrated proven efficacy as an adjunct treatment for the maintenance treatment of bipolar I disorder."
Launched in 1997, SEROQUEL has been prescribed to millions of patients worldwide. It is approved in 88 countries for the treatment of schizophrenia, in 79 countries for the treatment of bipolar mania, and in 11 countries including the U.S. for the treatment of bipolar depression.