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

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00619892
• Collaborator: AstraZeneca (Industry)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 46
• Patients Per Site Per Month: 0.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Panic Disorder	Drug: quetiapine XR; Drug: placebo	Phase 4

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
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An 8-week, Randomized, Double-Blind, Placebo-Controlled Trial of Seroquel SR Co-administration for SSRI-Resistant, Comorbid Panic Disorder
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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).	Drug: quetiapine XR; Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.; Other Names: Seroquel SR Seroquel XR
Placebo Comparator: Placebo Subjects received identical-appearing placebo tablets provided by Astra Zeneca (50, 200, and 300 mg designations).	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.; Other Names: Astra Zeneca placebo

Outcome Measures

Primary Outcome Measures

1. Change in Mean Total Panic Disorder Severity Scale (PDSS) Scores [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 Outcome Measures

1. 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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Outpatient Center, Psychiatry	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University
• AstraZeneca

Investigators

• Principal Investigator: Andrew W. Goddard, M.D., Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT00619892
• Other Study ID Numbers: 0703-22; IRUSQUET0445
• First Posted: Feb 21, 2008
• Last Update Posted: Jan 21, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Indiana University: SSRI Resistant; Seroquel SR; Seroquel XR; Panic Disorder; Comorbid Panic Disorder; Quetiapine SR; Quetiapine XR
• Additional relevant MeSH terms: Disease; Panic Disorder; Quetiapine Fumarate

Study Results

Participant Flow

Arm/Group Title	Quetiapine SR	Placebo
Arm/Group Description	quetiapine SR: Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.	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.
Period Title: Overall Study
STARTED	13	13
COMPLETED	10	11
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Quetiapine	Placebo	Total
Arm/Group Description	Quetiapine SR: Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.	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.	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	13 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.5 (9.6)	35.5 (16.8)	35.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	10 76.9%	8 61.5%	18 69.2%
Male	3 23.1%	5 38.5%	8 30.8%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%
Panic Disorder Severity Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	14.8 (3.6)	13.7 (3)	14.3 (3.3)
Clinical Global Impression-Severity Scale (CGI-S) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.8 (0.8)	4.4 (0.7)	4.6 (0.8)
Hamilton Anxiety Rating Scale (HAM-A) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.2 (6.8)	17 (5.2)	19.1 (6.0)
Hamilton Depression Rating Scale (HAM-D) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	14.6 (6.2)	11.5 (5.1)	13.1 (5.7)
Pittsburgh Sleep Quality Index (PSQI) sleep hours (hours slept per night) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours slept per night]	6.2 (1.3)	6.7 (1.6)	6.5 (1.5)
Pittsburgh Sleep Quality Index (PSQI) sleep quality (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.9 (0.6)	2.3 (0.6)	2.6 (0.6)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine SR	Placebo
Arm/Group Description	quetiapine SR: Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.	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.
Measure Participants	13	13
Mean (Standard Deviation) [units on a scale]	-5.3 (4.7)	-5.6 (4.8)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine XR	Placebo
Arm/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). quetiapine XR: Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.	Subjects received identical-appearing placebo tablets provided by Astra Zeneca (50, 200, and 300 mg designations). 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.
Measure Participants	13	13
Decrease in HAM-D scores	5.0 (5.2)	3.8 (3.6)
Decrease in HAM-A scores	6.8 (8.1)	5.5 (4.7)
Increase in PSQI sleep quality scores	1.3 (0.5)	1.3 (1.0)

Adverse Events

Arm/Group Title	Quietapine Group		Placebo Group
Arm/Group Description	quetiapine SR: Subjects will receive daily dosing at night, with a flexible dosing schedule, 50-400 mg.		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.
All Cause Mortality
	Quietapine Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Quietapine Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Quietapine Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/13 (76.9%)		5/13 (38.5%)
Gastrointestinal disorders
Constipation	3/13 (23.1%)	3	1/13 (7.7%)	1
Weight Loss	1/13 (7.7%)	1	0/13 (0%)	0
Weight Gain	0/13 (0%)	0	1/13 (7.7%)	1
Musculoskeletal and connective tissue disorders
Leg Pain	1/13 (7.7%)	1	1/13 (7.7%)	1
Muscle Aches	0/13 (0%)	0	2/13 (15.4%)	2
Nervous system disorders
Somnolence	10/13 (76.9%)	10	5/13 (38.5%)	5
Dry Mouth	3/13 (23.1%)	3	0/13 (0%)	0
Dizziness	2/13 (15.4%)	2	3/13 (23.1%)	3
Restlessness	2/13 (15.4%)	2	4/13 (30.8%)	4
Insomnia	1/13 (7.7%)	1	3/13 (23.1%)	3
Increased Appetite	1/13 (7.7%)	1	2/13 (15.4%)	2
Shakiness	1/13 (7.7%)	1	0/13 (0%)	0
Psychiatric disorders
Anxiety	4/13 (30.8%)	4	0/13 (0%)	0
Derealization	2/13 (15.4%)	2	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.