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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Naomi M. Simon, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00113295
First received: June 7, 2005
Last updated: March 20, 2014
Last verified: March 2014
Results First Received: May 16, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Anxiety Disorder
Interventions: Drug: Continued Paroxetine CR
Drug: Quetiapine
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
One hundred and one individuals were recruited through advertisement and clinical referral from February 2004 to June 2007, signed consent, and participated in a screening visit. Fifty-four individuals (53.5%) with GAD met the study entry criteria and initiated paroxetine CR in phase 1 of the trial.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Seven patients did not complete phase 1. Of phase 1 completers, 21 were not randomized. Twenty-two patients were randomized, 11 to quetiapine and 11 to placebo augmentation.

*Note that the data reported throughout the results section are from Phase 2 only.


Reporting Groups
  Description
Quetiapine, 25-400mg/Day Augmentation of Continued Paroxetine 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.
Placebo Augmentation of Continued Paroxetine 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.

Participant Flow:   Overall Study
    Quetiapine, 25-400mg/Day Augmentation of Continued Paroxetine     Placebo Augmentation of Continued Paroxetine  
STARTED     11     11  
COMPLETED     6     10  
NOT COMPLETED     5     1  
Adverse Event                 4                 1  
Unrelated Medical Illness                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Eligible participants were men or women aged 18 and older with a primary diagnosis of DSM-IV GAD.

Reporting Groups
  Description
Quetiapine, 25-400mg/Day Augmentation of Continued Paroxetine Individuals 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.
Placebo Augmentation of Continued Paroxetine Individuals received placebo augmentation of continued paroxetine CR at the week 10 dose level.
Total Total of all reporting groups

Baseline Measures
    Quetiapine, 25-400mg/Day Augmentation of Continued Paroxetine     Placebo Augmentation of Continued Paroxetine     Total  
Number of Participants  
[units: participants]
  11     11     22  
Age  
[units: years]
Mean ± Standard Deviation
     
At Phase 2 Baseline     43.8  ± 12.5     40.5  ± 11.2     42.2  ± 11.7  
Gender, Customized  
[units: participants]
     
Phase 2 Baseline Females     4     7     11  
Phase 2 Baseline Males     7     4     11  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     1     3     4  
White     10     8     18  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
HAM-A [1]
[units: units on a scale]
Mean ± Standard Deviation
  16.27  ± 5.04     15.82  ± 4.77     16.05  ± 4.8  
CGI-S [2]
[units: Units on a scale]
Mean ± Standard Deviation
  3.64  ± 0.67     3.91  ± 0.83     3.77  ± 0.75  
MADRS [3]
[units: units on a scale]
Mean ± Standard Deviation
  11.45  ± 1.93     12.36  ± 4.80     11.91  ± 3.66  
Q-LES-Q [4]
[units: units on a scale]
Mean ± Standard Deviation
  45.13  ± 10.6     45.89  ± 8.88     45.51  ± 9.77  
[1] 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.
[2] The Clinical Global Impression of Improvement (CGI-I) measures illness severity and improvement. The patient's current condition is compared to the patient's baseline condition on a seven-point scale. The condition is rated as 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.
[3] The Montgomery–Asberg Depression Rating Scale (MADRS) measures depressive symptoms.
[4] The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) measures the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.   [ Time Frame: Baseline and Week 18 ]

2.  Secondary:   Remission (HAM-A ≤ 7)   [ Time Frame: Week 18 (Study Endpoint) ]

3.  Secondary:   Response, Clinical Global Impression of Improvement (CGI-I)   [ Time Frame: Week 18 (Phase 2 Endpoint) ]

4.  Secondary:   Depressive Symptoms, Montgomery–Asberg Depression Rating Scale (MADRS)   [ Time Frame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint) ]

5.  Secondary:   The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).   [ Time Frame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint) ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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:  
Name/Title: Naomi M. Simon, M.D., M.Sc.
Organization: Massachusetts General Hospital
phone: (617) 726-7913
e-mail: nsimon@partners.org


No publications provided


Responsible Party: Naomi M. Simon, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00113295     History of Changes
Other Study ID Numbers: 2003-P001805
Study First Received: June 7, 2005
Results First Received: May 16, 2013
Last Updated: March 20, 2014
Health Authority: United States: Institutional Review Board