By Chris Berrie
LISBON, Portugal -- January 27, 2009 -- An extended-release (XR) formulation of the atypical antipsychotic quetiapine is well tolerated and more effective than placebo in the treatment of acute depressive episodes in patients with bipolar I and II disorder, according to results of a multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase 3 study.
Björn Paulsson, MD, AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, discussed the results in a presentation on January 25 on behalf of the study authors here at the European Psychiatry Association (EPA) 17th Annual Meeting.
The researchers enrolled outpatients aged 18 to 65 years with a clinical diagnosis of bipolar I or II disorder with or without rapidly cycling disease, who had an acute episode of depression. Further criteria included a total score of 20 or greater on the 17-item Hamilton Rating Scale for Depression (HAM-D17), an item 1 score of 2 or greater on the HAM-D17, and total score no greater than 12 on the Young Mania Rating Scale (YMRS).
The primary outcome was change from baseline to week 8 on total score of the Montgomery-Äsberg Depression Rating Scale (MADRS). The secondary outcomes included primary outcome subgroups, rates of response, and changes in Clinical Global Impression-Bipolar Disorder-Severity of Illness (CGI-BP-S) score.
Patient baseline demographics showed no differences between the placebo and quetiapine XR groups for bipolar I disorder (80.3% vs 80.5%, respectively), rapid cycling (27.7% vs 27.1%), mean MADRS score (30.1 vs 29.8), HAM-D17 score (24.6 vs 24.8), and CGI-BP-S score (4.4 vs 4.5).
After a washout period of up to 28 days, 137 patients were randomised to placebo and 133 to quetiapine XR 300 mg QD for 8 weeks. Quetiapine XR dosing was tapered through 50, 100, 200, and 300 mg over the first 4 days and then was maintained. Concomitant psychoactive drugs allowed were lorazepam, zolpidem tartrate, zaleplon, zopicione, and chloral hydrate.
Mean ages were 39.9 years in the quetiapine group and 39.0 years in the placebo group; men made up 37.2% and 33.8%, respectively, of each group.
Quetiapine XR treatment was significantly more effective than placebo for reduction in mean MADRS scores from week 1 through week 8. At week 8, reductions in mean MADRS scores were 17.4 for quetiapine XR and 11.9 for placebo (P < .001) and were similar for the bipolar I (P < .001) and 2 (P < .05) analyses and for patients without (P < .001) and with (P < .01) rapid cycling.
For individual MADRS items, 8 of 10 were significantly reduced with quetiapine XR over placebo (P < .05 to P < .001), with no effects on "lassitude" and "suicidal thoughts." These benefits for quetiapine XR over placebo were also reflected in the remaining secondary outcomes.
Rates of adverse events and withdrawal from the study were both higher for quetiapine XR than placebo, with the most common adverse effects being dry mouth (37.2 vs 7.1, respectively), somnolence (29.2% vs 5.7%), and sedation (23.4 vs 7.1%).
According to Dr. Paulsson, these findings show that quetiapine XR is efficacious for acute depressive episodes in patients with bipolar I and II disorder.
He referred to a parallel study by his team of patients with bipolar I acute-manic-phase [Abstract P1143], in which the findings showed that quetiapine XR is also efficacious in treating manic symptoms.
Funding for this study was provided by AstraZeneca Pharmaceuticals LP.
[Presentation title: Effectiveness of Extended-Release Formulation of Quetiapine as Monotherapy for the Treatment of Acute Bipolar Depression. Abstract P1144]
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