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

Indiana University

Status and phase: Completed; Phase 4

Conditions: Panic Disorder

Treatments: Drug: quetiapine XR; Drug: placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00619892

0703-22

IRUSQUET0445 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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26 participants in 2 patient groups, including a placebo group

Quetiapine XR

Active Comparator group

Description:

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).

Treatment:

Drug: quetiapine XR

Placebo

Placebo Comparator group

Description:

Subjects received identical-appearing placebo tablets provided by Astra Zeneca (50, 200, and 300 mg designations).

Treatment:

Drug: placebo