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Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder

Primary Purpose

Anxiety Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Continued Paroxetine CR
Quetiapine
Placebo
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anxiety Disorder focused on measuring generalized anxiety disorder, pharmacotherapy, treatment refractory, double-blind

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male and female outpatients, age 18-72. Primary diagnosis of generalized anxiety disorder. Patients on concurrent benzodiazepines will be entered into the trial if they remain symptomatic despite stable doses for at least one month Exclusion Criteria: Pregnant or lactating women or other women of child bearing potential not using acceptable means of birth control Patients with a primary diagnosis of major depression, dysthymia, panic disorder or social phobia. Patients with current or history of bipolar disorder, schizophrenia or other psychotic conditions Patients with post-traumatic stress disorder or obsessive-compulsive disorder current in the past 6 months. Patients with a history of alcohol or substance abuse or dependence within the last six months. Patients with significant unstable medical illness. Ongoing psychotherapy directed toward the treatment of generalized anxiety disorder. History of hypersensitivity to paroxetine CR, paroxetine or quetiapine. History of cataracts. Concurrent use of psychotropic medications including buspirone and antidepressants. Patients must have discontinued buspirone or antidepressant therapy at least two weeks prior to study entry, and fluoxetine at least four weeks prior, but no patient will be taken off effective medication. Concomitant use of herbs and dietary supplements with known psychotropic properties, including St John's Wort, Kava, Valerian, Gingko, Ginseng, ephedra and weight loss supplements. Other than such agents with known psychotropic properties, no over the counter medications are exclusionary.

Sites / Locations

  • Massachusetts General Hospital
  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Paroxetine CR and Placebo

Quetiapine and continued paroxetine CR

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.
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.

Secondary Outcome Measures

Remission (HAM-A ≤ 7)
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)
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)
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).
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.

Full Information

First Posted
June 7, 2005
Last Updated
March 20, 2014
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00113295
Brief Title
Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
Official Title
Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to examine the safety and efficacy of quetiapine for generalized anxiety disorder patients who remain symptomatic despite treatment with paroxetine CR.
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anxiety Disorder
Keywords
generalized anxiety disorder, pharmacotherapy, treatment refractory, double-blind

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Paroxetine CR and Placebo
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Quetiapine and continued paroxetine CR
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Continued Paroxetine CR
Intervention Type
Drug
Intervention Name(s)
Quetiapine
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.
Description
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.
Time Frame
Baseline and Week 18
Secondary Outcome Measure Information:
Title
Remission (HAM-A ≤ 7)
Description
Remission was measured as a secondary outcome using a score of less than or equal to 7 on the Hamilton Anxiety Scale (HAM-A).
Time Frame
Week 18 (Study Endpoint)
Title
Response, Clinical Global Impression of Improvement (CGI-I)
Description
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.
Time Frame
Week 18 (Phase 2 Endpoint)
Title
Depressive Symptoms, Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
Title
The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).
Description
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.
Time Frame
Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female outpatients, age 18-72. Primary diagnosis of generalized anxiety disorder. Patients on concurrent benzodiazepines will be entered into the trial if they remain symptomatic despite stable doses for at least one month Exclusion Criteria: Pregnant or lactating women or other women of child bearing potential not using acceptable means of birth control Patients with a primary diagnosis of major depression, dysthymia, panic disorder or social phobia. Patients with current or history of bipolar disorder, schizophrenia or other psychotic conditions Patients with post-traumatic stress disorder or obsessive-compulsive disorder current in the past 6 months. Patients with a history of alcohol or substance abuse or dependence within the last six months. Patients with significant unstable medical illness. Ongoing psychotherapy directed toward the treatment of generalized anxiety disorder. History of hypersensitivity to paroxetine CR, paroxetine or quetiapine. History of cataracts. Concurrent use of psychotropic medications including buspirone and antidepressants. Patients must have discontinued buspirone or antidepressant therapy at least two weeks prior to study entry, and fluoxetine at least four weeks prior, but no patient will be taken off effective medication. Concomitant use of herbs and dietary supplements with known psychotropic properties, including St John's Wort, Kava, Valerian, Gingko, Ginseng, ephedra and weight loss supplements. Other than such agents with known psychotropic properties, no over the counter medications are exclusionary.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naomi M Simon, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathryn Connors, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mghanxiety.org
Description
The Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital

Learn more about this trial

Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder

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