P0161 - A double-blind, placebo-controlled study with acute and continuation phase of Quetiapine and Paroxetine in adults with bipolar depression (Embolden II)

Abstract

Background and Aims:

Evaluate efficacy and tolerability of quetiapine and paroxetine monotherapy for major depressive episodes in bipolar disorder during an acute 8-week period and up to 52-week continuation phase.

Methods:

740 patients (478 bipolar I, 262 bipolar II) were randomized to quetiapine 300mg/d (n=245), quetiapine 600mg/d (n=247), paroxetine 20mg/d (n=122), or placebo (n=126) for 8 weeks. Primary endpoint was change from baseline to 8 weeks in MADRS total score. After 8 weeks, patients with MADRS ≤12 and YMRS ≤12 entered a 26- to 52-week continuation phase of quetiapine (300mg/d or 600mg/d) or placebo. Patients on paroxetine received 300mg/d of quetiapine (continuation phase results not included here and to be presented separately).

Results:

LSM MADRS score change at 8 weeks was -16.19 (quetiapine 300mg/d),-16.31 (quetiapine 600mg/d), -13.76 (paroxetine), and -12.60 (placebo; P<0.001 for both quetiapine doses, P=0.313 for paroxetine, versus placebo; LOCF ANCOVA). Quetiapine (both doses)-treated patients showed significantly greater improvements (P≤0.05) in MADRS response rate, HAM-D, CGI-BP-S, CGI-BP-Change, HAM-A, and MADRS item 10 (suicidal thoughts) at Week 8 versus placebo; MADRS remission rates improved with quetiapine 600mg/d versus placebo (P=0.012). Paroxetine improved HAM-A scores versus placebo (P=0.033).

Most common adverse events considered drug-related included dry mouth, somnolence, sedation, and dizziness with quetiapine (both doses); dry mouth, sedation, headache, insomnia, and nausea with paroxetine.

Conclusions:

Quetiapine (300mg/d or 600mg/d) was more effective than placebo for the treatment of acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.