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

Anxiety Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00113295
• Other study ID #: 2003-P001805
• Status: Completed
• Phase: Phase 4
• First received: June 7, 2005
• Last updated: March 20, 2014
• Start date: February 2004
• Est. completion date: November 2007

Study information

• Verified date: March 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders

Intervention

Drug:
• Continued Paroxetine CR

• Quetiapine

• Placebo

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and Week 18	No
Secondary	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).	Week 18 (Study Endpoint)	No
Secondary	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.	Week 18 (Phase 2 Endpoint)	No
Secondary	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.	Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)	No
Secondary	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.	Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)	No

External Links

•   The Center for Anxiety and Traumatic Stress Disorders at Massachusetts General Hospital