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

NCT00113295 | Completed Phase 4 Results DMC

• 1 other identifier: 2003-P001805
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Anxiety Disorder

Keywords

generalized anxiety disorder; pharmacotherapy; treatment refractory; double-blind

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Remission (HAM-A ≤ 7)

  Week 18 (Study Endpoint)

• Response, Clinical Global Impression of Improvement (CGI-I)

  Week 18 (Phase 2 Endpoint)

• Depressive Symptoms, Montgomery-Asberg Depression Rating Scale (MADRS)

  Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)

• The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

  Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)

Study Arms (2)

Paroxetine CR and Placebo

ACTIVE COMPARATOR

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

Quetiapine and continued paroxetine CR

EXPERIMENTAL

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

Interventions

Continued Paroxetine CR DRUG

Paroxetine CR and Placebo; Quetiapine and continued paroxetine CR

Quetiapine DRUG

Quetiapine and continued paroxetine CR

Placebo DRUG

Paroxetine CR and Placebo

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

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

MeSH Terms

Conditions

Anxiety Disorders; Generalized Anxiety Disorder

Interventions

Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Relatively small sample size of the randomized controlled phase (phase 2); conclusions from the study are limited to low power; improvement in Phase I open label paroxetine CR may include "placebo" response to ancillary aspects of a treatment study.

Results Point of Contact

• Title: Naomi M. Simon, M.D., M.Sc.
• Organization: Massachusetts General Hospital

nsimon@partners.org

(617) 726-7913

Study Officials

• Naomi M Simon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Kathryn Connors, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Anxiety and Traumatic Stress Disorders

Study Record Dates

• First Submitted: June 7, 2005
• First Posted: June 8, 2005
• Study Start: February 1, 2004
• Primary Completion: February 1, 2007
• Study Completion: November 1, 2007
• Last Updated: April 23, 2014
• Results First Posted: April 23, 2014

Record last verified: 2014-03

Locations

US (2)