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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An 8-week, Randomized, Double-Blind, Placebo-Controlled Trial of Seroquel SR Co-administration for SSRI-Resistant, Comorbid Panic Disorder

Conditions
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Panic Disorder

Intervention / Treatment
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* Drug: quetiapine XR
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quetiapine XR<br>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<br>* Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.<br>* Other names: Seroquel XR;|
| Placebo Comparator: Placebo<br>Subjects received identical-appearing placebo tablets provided by Astra Zeneca (50, 200, and 300 mg designations). | Drug: placebo<br>* Subjects will receive daily dosing at night with caplets matching the appearance of the active drug. However, caplets will not contain any active medication.<br>* Other names: Astra Zeneca placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores | 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. | Baseline and the end of 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | Comparing baseline and the end of 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SSRI Resistant, Seroquel SR, Seroquel XR, Panic Disorder, Comorbid Panic Disorder, Quetiapine SR, Quetiapine XR