Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
Drug: Continued Paroxetine CR
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder|
- Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint. [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]
Symptoms of generalized anxiety disorder as measured by the Hamilton Anxiety Scale (HAM-A) at week 18/study endpoint. Each item is scored on a scale from 0 (not present) to 4 (severe) with a total score range of 0-56. Changes in HAM-A scores are calculated as the difference between the baseline HAM-A scores and scores at week 18/study endpoint.
The 14-item Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1959) was developed to assess anxiety in a clinical population. It is considered a measure of general anxiety across anxiety disorders, in addition to being a gold standard measure for GAD.
- Remission (HAM-A ≤ 7) [ Time Frame: Week 18 (Study Endpoint) ] [ Designated as safety issue: No ]Remission was measured as a secondary outcome using a score of less than or equal to 7 on the Hamilton Anxiety Scale (HAM-A).
- Response, Clinical Global Impression of Improvement (CGI-I) [ Time Frame: Week 18 (Phase 2 Endpoint) ] [ Designated as safety issue: No ]Response was measured as a secondary outcome using the Clinical Global Impression of Improvement (CGI-I). Response was defined as a score of 1 ["very much improved"] or 2 ["much improved"] at study endpoint.
- Depressive Symptoms, Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint) ] [ Designated as safety issue: No ]Depressive symptoms were measured at a secondary outcome using the Montgomery-Asberg Depression Rating Scale (MADRS). Each item is scored on a scale of 1-6; The total score range is 0-60, with higher scores indicated higher levels of depression severity.
- The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). [ Time Frame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint) ] [ Designated as safety issue: No ]The 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is used to assess quality of life changes with treatment. Total scores range from 14-70, with higher levels of satisfaction yielding higher scores.
|Study Start Date:||February 2004|
|Study Completion Date:||November 2007|
|Primary Completion Date:||February 2007 (Final data collection date for primary outcome measure)|
Active Comparator: Paroxetine CR and Placebo
Eleven individuals were randomized to plaecbo augmentation of continued paroxetine CR at the week 10 dose level. In the first phase of the study, individuals started at 12.5 mg/day of paroxetine and flexibly titrated up to a maximum of 62.5 mg/day by week 10. Individuals who did not achieve remission and were randomized into the placebo group received placebo augmentation of continued paroxetine CR at the week 10 dose level.
|Drug: Continued Paroxetine CR Drug: Placebo|
Experimental: Quetiapine and continued paroxetine CR
Eleven individuals were randomized to quetiapine augmentation of continued paroxetine CR at the week 10 dose level. In the first phase of the study, individuals started at 12.5 mg/day of paroxetine and flexibly tirated up to a maximum of 62.5 mg/day by week 10. Individuals who did not receive remission and were randomized to receive quetiapine started at 25 mg at bedtime for the first week, then flexibly dosed based on response and tolerability to a maximum of 200 mg BID by week 16.
|Drug: Continued Paroxetine CR Drug: Quetiapine|
Generalized anxiety disorder (GAD) is a relatively common condition affecting 5% of the population, with a typically chronic course and associated with significant psychosocial impairment and decreased quality of life (Schweizer, 1995). Although a number of therapeutic agents demonstrate some efficacy in the treatment of generalized anxiety disorder, only a minority of anxious patients experience remission with initial treatment.
The purpose of this study is to examine the efficacy of one strategy, the addition of quetiapine, for the treatment of patients with GAD who remain refractory despite an adequate treatment trial with a selective serotonin reuptake inhibitor (SSRI). This is an investigator-initiated augmentation study of an already approved drug for a different indication. Quetiapine is a novel antipsychotic agent with potent effects at the serotonergic, as well as dopaminergic receptor, and a more favorable side effect profile than standard neuroleptics, including a low potential to cause extrapyramidal symptoms.
This is a two phase, 18-week research study in which participants who remain symptomatic at the end of one phase (10 weeks) enter into the next phase. In phase I, all participants receive paroxetine CR (Paxil CR) for 10 weeks. Participants who continue to have anxiety symptoms will enter the 8-week Phase II, in which they continue taking Paxil CR and they will also be randomly assigned (by chance, like a flip of a coin) to receive quetiapine (Seroquel) or placebo (contains no active medication).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00113295
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Naomi M Simon, MD||Massachusetts General Hospital|
|Principal Investigator:||Kathryn Connors, MD||Duke University|