Clinical trial NCT00113295: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anxiety Disorder
Keywords: generalized anxiety disorder
pharmacotherapy
treatment refractory
double-blind
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2005-06-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.
timeFrame: Baseline and Week 18
Secondary outcomes:
measure: Remission (HAM-A ≤ 7)
timeFrame: Week 18 (Study Endpoint)
measure: Response, Clinical Global Impression of Improvement (CGI-I)
timeFrame: Week 18 (Phase 2 Endpoint)
measure: Depressive Symptoms, Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
measure: The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).
timeFrame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Massachusetts General Hospital
name: Naomi M Simon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Kathryn Connors, MD
role: PRINCIPAL_INVESTIGATOR
References: