A Study of Quetiapine SR (Seroquel SR) to Treat SSRI-Resistant, Comorbid Panic Disorder Patients

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00619892
First received: February 11, 2008
Last updated: December 15, 2015
Last verified: December 2015
  Purpose
The primary objective of this study is to test the hypothesis that a SSRI plus quetiapine SR (Seroquel SR) will result in superior early (first 1-3 weeks of treatment) stabilization of panic symptoms in SSRI-resistant, comorbid Panic Disorder patients versus a SSRI plus placebo.

Condition Intervention Phase
Panic Disorder
Drug: quetiapine XR
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An 8-week, Randomized, Double-Blind, Placebo-Controlled Trial of Seroquel SR Co-administration for SSRI-Resistant, Comorbid Panic Disorder

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores [ Time Frame: Baseline and the end of 8 weeks of treatment ] [ Designated as safety issue: No ]
    Possible total scores on the PDSS range from 0-28. The outcome measure represents the change, between baseline and the end of 8 weeks of treatment, in the the total PDSS scores. Lower scores indicate less severe panic disorder symptoms. A negative mean change in the scores at the end of 8 weeks represents a decrease in severity of panic disorder symptoms.


Secondary Outcome Measures:
  • Change in Scores in Measurements of Depressive Symptoms (Hamilton Depression Rating Scale, HAM-D), Generalized Anxiety Symptoms (Hamilton Anxiety Rating Scale, HAM-A) and the Sleep Quality Item of the Pittsburgh Sleep Quality Index (PSQI). [ Time Frame: Comparing baseline and the end of 8 weeks of treatment ] [ Designated as safety issue: No ]
    Subjects scores on secondary efficacy measures were measured, comparing baseline and the end of 8 weeks of treatment, including the Hamilton Depression Rating Scale, HAM-D, which has 21 items, with scores ranging from 0-66; the Hamilton Anxiety Rating Scale, HAM‑A, which has 14 items, with scores ranging from 0-56; and the sleep quality item of the PSQI, a four-point scale rating sleep quality as very good, fairly good, fairly bad or very bad.


Enrollment: 26
Study Start Date: February 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Quetiapine XR
Our target daily dose for quetiapine XR was 200 mg/day. The detailed quetiapine XR dosing guidelines were as follows: 50 mg 1 tab po at HS × 3 days, then, if 50 mg tolerated, increase to 50 mg 2 tabs at HS × 4 days; at the beginning of week 2, if the last dose was tolerated increase to 50 mg 3 tabs at HS × 3 days, then, if 150 mg tolerated, increase to 4 tabs at HS; at the beginning of week 3, if no efficacy & the 200 mg dose was well tolerated, increase to one 300 mg tab at HS-otherwise remain at 200 mg one tab at HS; at week 4 if still no improvement, & 300 mg was tolerable, increase to 200 mg tablet 2 at HS. From the beginning of week 5 to the end of the trial, quetiapine XR doses were held. We used quetiapine XR tablets provided by Astra Zeneca (50, 200, and 300 mg designations).
Drug: quetiapine XR
Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.
Other Names:
  • Seroquel SR
  • Seroquel XR
Placebo Comparator: Placebo
Subjects received identical-appearing placebo tablets provided by Astra Zeneca (50, 200, and 300 mg designations).
Drug: placebo
Subjects will receive daily dosing at night with caplets matching the appearance of the active drug. However, caplets will not contain any active medication.
Other Name: Astra Zeneca placebo

Detailed Description:

This was a single-site, double-blind, placebo-controlled (PLAC), randomized, parallel group (2 groups), 8-week, quetiapine extended release (XR) coadministration trial. SSRI resistance was determined either historically or prospectively. Patients were randomized if they remained moderately ill (CGI-S score ≥ 4). Change in the PDSS scale total score was the primary efficacy outcome measure. Responders were identified as those with a ≥50 % decrease from their baseline PDSS score. In the early weeks of therapy, XR was flexibly and gradually titrated from 50 to 400 mg/day.

Conclusions: This proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD. Quetiapine XR was generally well-tolerated. Important limitations were the small sample size, and the relatively low average dose of quetiapine XR used.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of written informed consent
  • Diagnosis of Panic Disorder by DSM-IV TR and confirmed by MINI plus interview
  • Females and males ages 18-65 years old
  • Female patients of childbearing potential must by using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrollment
  • Able to understand and comply with the requirements of the study
  • Have a CGI illness severity score = or > 4
  • Patients with comorbid major depression, dysthymia or other anxiety problems are eligible to participate as well.

Exclusion criteria:

  • Pregnancy or lactation
  • Any DSM-IV TR Axis I disorder not mentioned in the inclusion requirements
  • Suicidal or danger to self or others
  • Known intolerance to quetiapine fumarate or intolerance to SSRI therapy
  • Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrollment including but not limited to : ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
  • Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to : phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
  • Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomization
  • Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
  • Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV TR criteria within 4 weeks prior to enrollment
  • Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
  • Unstable or inadequately treated medical illness (e.g. angina pectoris, hypertension) as judged by the investigator
  • Involvement in the planning and conduct of the study
  • Previous enrollment or randomization of treatment in the present study
  • Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements
  • A patient with a diagnosis of Type I or Type II Diabetes Mellitus (DM)
  • An absolute neutrophil count (ANC) of 1.5 x 109 per liter
  • A lifetime history of a pre-existing CNS/neurological disorder e.g. epilepsy, TBI, brain tumor
  • Patient with severe personality disorders
  • Patients who have started a new course of psychotherapy (CBT, supportive, insight-oriented) within 1 month of the screening visit
  • Patients unwilling to refrain from participation in psychotherapy during the 9-week period of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619892

Locations
United States, Indiana
University Hospital Outpatient Center, Psychiatry
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
AstraZeneca
Investigators
Principal Investigator: Andrew W. Goddard, M.D. Indiana University
  More Information

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00619892     History of Changes
Other Study ID Numbers: 0703-22  IRUSQUET0445 
Study First Received: February 11, 2008
Results First Received: July 27, 2015
Last Updated: December 15, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
SSRI Resistant
Seroquel SR
Seroquel XR
Panic Disorder
Comorbid Panic Disorder
Quetiapine SR
Quetiapine XR

Additional relevant MeSH terms:
Disease
Panic Disorder
Anxiety Disorders
Mental Disorders
Pathologic Processes
Quetiapine Fumarate
Antipsychotic Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Tranquilizing Agents

ClinicalTrials.gov processed this record on May 25, 2016