An 8-week, Randomized, Double-Blind, Placebo-Controlled Trial of Seroquel SR Co-administration for SSRI-Resistant, Comorbid Panic Disorder
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Indiana University
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores
Study Overview
Brief Summary
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Exclusion Criteria
- Not provided
Arms & Interventions
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).
Intervention: quetiapine XR (Drug)
Placebo
Subjects received identical-appearing placebo tablets provided by Astra Zeneca (50, 200, and 300 mg designations).
Intervention: placebo (Drug)
Outcomes
Primary Outcomes
Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores
Time Frame: Baseline and the end of 8 weeks of treatment
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 Outcomes
- 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).(Comparing baseline and the end of 8 weeks of treatment)