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

NCT ID: NCT00619892

Last Updated: 2016-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2011-12-31

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.

Conditions

Panic Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

quetiapine XR

Intervention Type: DRUG

Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.

Placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Subjects will receive daily dosing at night with caplets matching the appearance of the active drug. However, caplets will not contain any active medication.

Interventions

quetiapine XR

Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Seroquel SR; Seroquel XR; Astra Zeneca placebo

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew W. Goddard, M.D.

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

University Hospital Outpatient Center, Psychiatry

Indianapolis, Indiana, United States

Countries

United States

References

Goddard AW, Mahmud W, Medlock C, Shin YW, Shekhar A. A controlled trial of quetiapine XR coadministration treatment of SSRI-resistant panic disorder. Ann Gen Psychiatry. 2015 Sep 15;14:26. doi: 10.1186/s12991-015-0064-0. eCollection 2015.

Reference Type: DERIVED

PMID: 26379759 (View on PubMed)

Other Identifiers

IRUSQUET0445

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

0703-22

Identifier Type: -

Identifier Source: org_study_id