Anxiety DisorderPhase 4NCT00113295
Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
A Phase 4 study testing Continued Paroxetine CR and Quetiapine in people with Anxiety Disorder, run by Massachusetts General Hospital at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Anxiety Disorder
- What is being tested?
- Continued Paroxetine CR and Quetiapine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2004to Nov 2007
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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.
Read the 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).
- Conditions
- Anxiety Disorder
- Being tested
- Continued Paroxetine CR, Quetiapine, Placebo
- Keywords
- generalized anxiety disorder, pharmacotherapy, treatment refractory, double-blind
- Medical subject headings
- Anxiety Disorders, Generalized Anxiety Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continued Paroxetine CRDrug
QuetiapineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Continued Paroxetine CR; Drug: Quetiapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 18
Secondary outcomes (4)
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).
Measured: Week 18 (Study Endpoint)
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.
Measured: Week 18 (Phase 2 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.
Measured: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
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.
Measured: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2005 (estimated)
- Study startFeb 2004
- Primary completionFeb 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anxiety DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Naomi M. Simon, Massachusetts General Hospital
- Investigators
- Naomi M Simon, MD, Principal investigator, Massachusetts General HospitalKathryn Connors, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00113295
- Sponsor's protocol ID
- 2003-P001805
- Status last verified
- Mar 2014
- First submitted
- 7 Jun 2005
- Last updated
- 23 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
- ClinicalTrials.gov ID
- NCT00113295
- Acronym / sponsor ID
- 2003-P001805
- Conditions
- Anxiety Disorder
- Keywords
- generalized anxiety disorder, pharmacotherapy, treatment refractory, double-blind
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Feb 2004
- Primary completion
- Feb 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 8 Jun 2005 (estimated)
- Results
- Posted 23 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paroxetine CR and Placebo | Active comparator | Drug: Continued Paroxetine CR, Drug: PlaceboEleven 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. |
| Quetiapine and continued paroxetine CR | Experimental | Drug: Continued Paroxetine CR, Drug: QuetiapineEleven 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. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint.
Time frame: Baseline and Week 18
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.
4 secondary outcomes
Remission (HAM-A ≤ 7)
Time frame: Week 18 (Study Endpoint)
Response, Clinical Global Impression of Improvement (CGI-I)
Time frame: Week 18 (Phase 2 Endpoint)
Depressive Symptoms, Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).
Time frame: Week 10 (Phase 1 Endpoint) and Week 18 (Phase 2 Endpoint)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Center for Anxiety and Traumatic Stress Disorders at Massachusetts General HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naomi M Simon, MD principal investigator
Massachusetts General Hospital
Kathryn Connors, MD principal investigator
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continued Paroxetine CR and Quetiapine in people with Anxiety Disorder, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Anxiety Scale (HAM-A) Score at Study Endpoint. (time frame: Baseline and Week 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2014; AzTrials last refreshed its copy on 8 Nov 2026.