Seroquel Study Gives Hope For Beating Depression In Bipolar Disorder

Main Category: Bipolar
Also Included In: Depression
Article Date: 04 Jun 2006 - 4:00 PDT

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Keeping the manic-depressive illness Bipolar Disorder under control may become simpler in future if psychiatrists implement new research findings from the BOLDER II study presented during the American Psychiatry Association's 159th annual meeting 20-25 May 2006.

Currently patients have to take three or four different drugs to control symptoms of mania and depression, keep moods on an even keel and to try and prevent relapse. Now, there is a prospect of one drug - the atypical antispsychotic, quetiapine (Seroquel) - being able to do the job of four, controlling symptoms at both ends of the spectrum and resolving feelings of anxiety without causing serious side effects.

Results of the randomised double-blind placebo-controlled BOLDER II study, involving 509 patients with bipolar depression, show quetiapine significantly and rapidly reduced symptoms of depression and anxiety within the first week of therapy compared to placebo and continued to relieve symptoms over the course of the 8-week study.

BOLDER II was conducted to repeat an earlier study, BOLDER 1. Both studies included patients with bipolar disorder types I or II reflecting disease of varying symptom severity. In each trial two doses of quetiapine (300 and 600mg) were tested against placebo. Improvements in depressive symptoms were measured on the Montgomery Asberg Depression Rating Scale (MADRS) scale. Anxiety was measured on the Hamilton Anxiety (HAM-A) rating scale while quality of life, energy levels and overall improvement were also measured on appropriate scales.

BOLDER II lead investigator Dr Michael Thase of University of Pittsburgh said: "The findings are remarkable because such a close replication of results in psychiatry is unusual." In clinical trials investigating depression there can be a large response to placebo making it hard to assess the true extent of an active treatment's therapeutic effect, he explained. "But In each of these two studies there was a clear-cut and early separation of the curves showing response to quetiapine and placebo. Response to both the 300mg and 600mg doses was almost identical." Response to depression was not associated with patients developing mania as a result of treatment, he added.

Joseph Calabrese, Professor of Psychiatry at University Hospitals of Cleveland, and a world leader in treatment of bipolar disorder, commented: "No other study in bipolar depression has shown such a large separation of the curves showing response to active medication and placebo as was seen in the BOLDER studies."

Suicidal thoughts reduced

Robert Hirschfield, Professor of Psychiatry at University of Texas, who conducted an analysis of bipolar II patients in the two BOLDER studies said: "On every item in the rating scales, including the core symptoms of depression - sadness and occurrence of suicidal thoughts - medication outperformed placebo." The effect on suicidal ideation gives hope that treatment might reduce the high incidence of suicide in this condition, he added. Over half of sufferers attempt suicide at some stage of their illness and 10-15 per cent succeed.

Richard Weisler, Professor of Psychiatry of Duke University, North Carolina who conducted an analysis of the bipolar 1 patients from both studies said the effect size of quetiapine over placebo (0.8) was large and robust. "This is some of the best data seen so far in bipolar depression" he commented. " If quetiapine is approved for bipolar depression it will be a wonderful new option in an area where an effective treatment is desperately needed because the suicide rate is high."

Quetiapine is already approved for the control of mania in bipolar disorder. In December 2005, FDA approval was sought to treat bipolar depression using quetiapine in the US. Studies still in progress in Europe are also investigating the drug's efficacy both in acute bipolar depressive episodes as well as in longer-term symptom control.

"My hunch is that since we know quetiapine works on both acute mania and depression that it will turn out to be good at stabilising the disease also," suggested Professor Calabrese. If this hypothesis proves correct patients may not need to take another medication to prevent relapses.

The BOLDER studies showed the average weight gained by patients receiving quetiapine was 1.3kg and 1.4 kg at eight weeks. This is low compared to weight-gain typically seen with another atypical antipsychotic used in bipolar disorder. The most common side effect of quetiapine therapy was dry mouth affecting around 40 per cent. Daytime sedation and somnolence affected around 30 per cent of patients. "Patients who experience these symptoms usually do so in the first couple of weeks," noted Prof Calabrese. "If they can be encouraged to remain on treatment for more than two weeks they may find symptoms less troublesome over time." Most patients will put up with some side effects if they feel the treatment is controlling their bipolar symptoms, he added. Only 8 per cent of patients taking 300mg quetiapine, and 11 per cent taking 600mg abandoned treatment because of adverse effects and there was no significant difference among treatment and placebo groups in the proportions of patients completing the study.

Olwen Glynn Owen

http://www.seroquel.com