Quetiapine monotherapy as treatment for anxiety symptoms in patients with bipolar depression: a pooled analysis of results from 2 double-blind, randomized, placebo-controlled studies

Abstract

Objective: To evaluate the efficacy and tolerability of quetiapine monotherapy for anxiety symptoms in patients with bipolar disorder experiencing depression in the BipOLar DEpRession (BOLDER I and II) studies.

Method: A post hoc analysis of anxiety symptoms in 1,051 acutely depressed patients with bipolar I or II disorder (DSM-IV) from 2 double-blind, randomized, placebo-controlled 8-week studies of quetiapine (300 or 600 mg once daily) was conducted. Anxiety symptoms were assessed using Hamilton Anxiety Rating Scale (HARS) total and psychic (items 1-6, 14) and somatic (items 7-13) anxiety subscale scores (mixed-model repeated measure and last-observation-carried-forward analysis of change from baseline at each assessment). The BOLDER I study was conducted between September 2002 and October 2003, and the BOLDER II study was conducted between June 2004 and August 2005.

Results: Mean baseline HARS total scores were similar across the treatment groups (300 mg/d: 18.9, 600 mg/d and placebo: both 18.6). There was a significantly greater improvement from baseline in mean HARS total scores at the first evaluation (week 1) in both quetiapine groups compared with placebo (300 mg/d: -4.6, P < .001 and 600 mg/d: -4.1, P = .003 vs placebo: -2.8). These improvements were sustained through week 8 with both quetiapine doses (300 mg/d: -10.1, P < .001 and 600 mg/d: -10.5, P < .001 vs placebo: -6.9). At week 8, there was also significant improvement from baseline in HARS psychic and somatic anxiety subscale scores compared with placebo (P < .001). The baseline severity of anxiety did not impact the improvement in depressive symptoms. Common adverse events included dry mouth, sedation, somnolence, and dizziness.

Conclusions: In this pooled analysis, quetiapine monotherapy was more effective than placebo and generally well tolerated for the treatment of both depressive and anxiety symptoms in patients with bipolar disorder.

Trial registration: clinicaltrials.gov Identifiers: NCT00060489 (BOLDER I) and NCT00083954 (BOLDER II).

Figures

Figure 1

Least Squares Mean Change From Baseline in MADRS Total Score at Each Assessment From Pooled Studies of Patients With Bipolar I or II Disorder Experiencing a Depressive Episode (MMRM) ‡P < .001. Abbreviations: MADRS = Montgomery-Asberg Depression Rating Scale, MMRM = mixed-model repeated measure.

Figure 2

Mean Percent Improvement From Baseline in Individual MADRS Items From Pooled Studies of Patients With Bipolar I and II Disorder Experiencing a Depressive Episode (MMRM)a aP values based on change from baseline MMRM analyses. *P < .05 versus placebo; †P < .01; ‡P < .001. Abbreviations: MADRS = Montgomery-Asberg Depression Rating Scale, MMRM = mixed-model repeated measure.

Figure 3

Least Squares Mean Change From Baseline in HARS Total Score at Each Assessment From Pooled Studies of Patients With Bipolar I or II Disorder Experiencing a Depressive Episode (MMRM) †P < .01. ‡P < .001. Abbreviations: HARS = Hamilton Rating Scale for Anxiety, MMRM = mixed-model repeated measure.

Figure 4

Mean Percent Improvement From Baseline in Individual HARS Items From Pooled Studies of Patients With Bipolar I and II Disorder Experiencing a Depressive Episode (MMRM)a aP values based on change from baseline MMRM analyses. *P < .05 placebo; †P < .01; ‡P < .001. Abbreviations: HARS = Hamilton Rating Scale for Anxiety, MMRM = mixed-model repeated measure.

Figure 5

Least Squares Mean Change From Baseline in MADRS Total Score Stratified According to Baseline Anxiety Level From Pooled Studies of Patients With Bipolar I and II Disorder Experiencing a Depressive Episode (ITT, LOCF ANCOVA) *P < .05 versus placebo. †P < .01. ‡P < .001. Abbreviations: HARS = Hamilton Rating Scale for Anxiety, ITT = intent-to-treat, LOCF ANCOVA = last-observation-carried-forward analysis of covariance, MADRS = Montgomery-Asberg Depression Rating Scale.

Figure 5

Least Squares Mean Change From Baseline in MADRS Total Score Stratified According to Baseline Anxiety Level From Pooled Studies of Patients With Bipolar I and II Disorder Experiencing a Depressive Episode (ITT, LOCF ANCOVA) *P < .05 versus placebo. †P < .01. ‡P < .001. Abbreviations: HARS = Hamilton Rating Scale for Anxiety, ITT = intent-to-treat, LOCF ANCOVA = last-observation-carried-forward analysis of covariance, MADRS = Montgomery-Asberg Depression Rating Scale.

Figure 5

Least Squares Mean Change From Baseline in MADRS Total Score Stratified According to Baseline Anxiety Level From Pooled Studies of Patients With Bipolar I and II Disorder Experiencing a Depressive Episode (ITT, LOCF ANCOVA) *P < .05 versus placebo. †P < .01. ‡P < .001. Abbreviations: HARS = Hamilton Rating Scale for Anxiety, ITT = intent-to-treat, LOCF ANCOVA = last-observation-carried-forward analysis of covariance, MADRS = Montgomery-Asberg Depression Rating Scale.