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

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

quetiapine XR

placebo

About this trial

This is an interventional treatment trial for Panic Disorder focused on measuring SSRI Resistant, Seroquel SR, Seroquel XR, Panic Disorder, Comorbid Panic Disorder, Quetiapine SR, Quetiapine XR

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

University Hospital Outpatient Center, Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Quetiapine XR

Placebo

Arm 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).

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

Outcomes

Primary Outcome Measures

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.

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).

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.

Full Information

NCT ID

NCT00619892

First Posted

February 11, 2008

Last Updated

December 15, 2015

Sponsor

Indiana University

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT00619892

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

February 2008 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Indiana University

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Panic Disorder

Keywords

SSRI Resistant, Seroquel SR, Seroquel XR, Panic Disorder, Comorbid Panic Disorder, Quetiapine SR, Quetiapine XR

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Quetiapine XR

Arm Type

Active Comparator

Arm 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).

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

quetiapine XR

Other Intervention Name(s)

Seroquel SR, Seroquel XR

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

placebo

Other Intervention Name(s)

Astra Zeneca placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores

Description

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.

Time Frame

Baseline and the end of 8 weeks of treatment

Secondary Outcome Measure Information:

Title

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).

Description

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.

Time Frame

Comparing baseline and the end of 8 weeks of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew W. Goddard, M.D.

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Outpatient Center, Psychiatry

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26379759

Citation

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.

Results Reference

derived

Panic Disorder

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial