Efficacy of Extended-release Quetiapine (Seroquel XR) as Adjunctive Therapy to Cognitive Behavioral Therapy in the Treat

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT01971203
• Collaborator: AstraZeneca (Industry)
• Enrollment: 62
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The primary objective of the study is to determine whether quetiapine extended-release in combination with cognitive behavioral therapy (CBT) is more effective than CBT plus placebo in treating depressive and anxiety symptoms in patients with both major depression and generalized anxiety disorder. Approximately 64 individuals (adults 18-65) will be randomly assigned to treatment group for 16 weeks. Weekly CBT sessions will be conducted lasting about 45 minutes and weekly visits with the study psychiatrist lasting about 20 minutes in which medication will be discussed. Both clinician administered and self-report measures will be used to compare groups before and after 16 weeks.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder; Generalized Anxiety Disorder	Drug: seroquel xr; Behavioral: CBT	N/A

Detailed Description

This study will evaluate the efficacy of quetiapine extended-release as adjunctive therapy to cognitive behavioral therapy (CBT) compared to CBT plus placebo in the treatment of patients with comorbid major depression and generalized anxiety disorder. We will also evaluate the quality of life in patients with comorbid MDD/GAD, the response and remission rates by treatment group, changes in sleep quality, and tolerability of adjunctive quetiapine to CBT.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-blind, Randomized, Active Controlled Study of the Efficacy and Safety of Extended-release Quetiapine Fumarate (Seroquel XR) as Adjunctive Medication Therapy to Cognitive Behavioral Therapy in the Treat,Ent of Patients With Comorbid Major Depression and Generalized Anxiety Disorder
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: seroquel xr quetiapine target dosage will be 150 mg/day, beginning at 50 mg/day 16 weeks of treatment including CBT	Drug: seroquel xr; Quetiapine target dosage will be 150 mg/day, beginning at 50 mg/day; Other Names: quetiapine XR
Placebo Comparator: placebo plus CBT treatment group receiving placebo pill plus CBT	Behavioral: CBT; 16 weeks of treatment; Other Names: cognitive behavioral therapy

Outcome Measures

Primary Outcome Measures

1. MADRS [baseline and 16 weeks]

   Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-administered, with overall score ranges from 0 (normal) to 54 (severe depression). Score at 16 weeks as compared to baseline.

Secondary Outcome Measures

1. HAM-A [baseline and 16 weeks]

   Hamilton Rating Scale for Anxiety (HAM-A) is a 14-item clinician-administered scale measuring symptoms with total scale from 0 (not present) to 56 (severe) to severe anxiety.

2. Clinical Global Impression Scales for Severity and Improvement [up to 16 weeks]

   The Clinical Global Impression Scales for Severity and Improvement (CGI-I and CGI-S), both clinician rated, measures overall severity of symptoms and level of improvement on a seven-point scale from 0 (not applicable or not assessed) to 7, where 7 is the most severe. In order for a participant to be considered a treatment responder, he or she must receive a score of 1 (not ill or very much improved) or 2 (borderline mentally ill or much improved).

3. Changes in Sexual Functioning Questionnaire (CSFQ) [baseline and week 16]

   Changes in Sexual Functioning Questionnaire (CSFQ) at week 16 as compared to baseline. The CSFQ assesses interest, functioning, and satisfaction in sex on a six-point scale, where 1 is greater than normal and 6 is totally absent, with full range from 5 (greater than normal) to 30 (totally absent).

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

• A diagnosis of both major depression (single episode or recurrent) and generalized anxiety disorder by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)

• Females and/or males aged 18 to 65 years

• Female patients of childbearing potential must be 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

Exclusion Criteria:

• Pregnancy or lactation

• Any history of psychosis, bipolar disorder, schizophrenia, eating disorders or OCD

• Imminent risk of suicide or a danger to self or others

• Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator

• 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

• Substance abuse by DSM-IV criteria within 6 months prior to enrollment

• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment

• Unstable or inadequately treated medical illness (e.g. diabetes, 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 to enrollment into this study or longer in accordance with local requirements

• A patient with Diabetes Mellitus (DM)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai
• AstraZeneca

Investigators

• Principal Investigator: Jack Hirschowitz, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jack Hirschowitz, Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01971203
• Other Study ID Numbers: GCO 09-0807
• First Posted: Oct 29, 2013
• Last Update Posted: Feb 15, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Jack Hirschowitz, Professor, Icahn School of Medicine at Mount Sinai: seroquel XR; quetiapine XR; major depression; generalized anxiety disorder; CBT; co-morbid MDD
• Additional relevant MeSH terms: Disease; Anxiety Disorders; Depressive Disorder; Depressive Disorder, Major; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	Participants were recruited through the Mount Sinai faculty referrals, medical center employee newsletter, and advertisements in local newspapers, radio, and craigslist.
Pre-assignment Detail	Ninety-four participants were screened - 10 participants did not meet study eligibility, 22 elected not to continue. 62 participants were randomized, but 7 never returned for the first visit, leaving 55 participants who began treatment.

Arm/Group Title	Seroquel XR Plus CBT	Placebo Plus CBT
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day with an intended titration schedule reaching 150 mg over the first three weeks, adding one pill per week. . If a participant could not tolerate the increased dose, then dosage was decreased to either one or two pills a day. All participants who completed the study received 16 sessions of CBT and discontinued medication at 16 weeks. Although conducted weekly, CBT and medication schedules did not always terminate at the same time.	matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy
Period Title: Overall Study
STARTED	26	29
COMPLETED	17	21
NOT COMPLETED	9	8

Baseline Characteristics

Arm/Group Title	Seroquel XR Plus CBT	Placebo Plus CBT	Total
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day with an intended titration schedule reaching 150 mg over the first three weeks, adding one pill per week. . If a participant could not tolerate the increased dose, then dosage was decreased to either one or two pills a day. All participants who completed the study received 16 sessions of CBT and discontinued medication at 16 weeks. Although conducted weekly, CBT and medication schedules did not always terminate at the same time.	matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy	Total of all reporting groups
Overall Participants	30	32	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.93 (13.68)	39.88 (12.81)	39.90 (13.12)
Sex: Female, Male (Count of Participants)
Female	17 56.7%	21 65.6%	38 61.3%
Male	13 43.3%	11 34.4%	24 38.7%
Race/Ethnicity, Customized (Count of Participants)
White	19 63.3%	22 68.8%	41 66.1%
Black	4 13.3%	4 12.5%	8 12.9%
Hispanic	2 6.7%	3 9.4%	5 8.1%
Asian	3 10%	1 3.1%	4 6.5%
Other	2 6.7%	1 3.1%	3 4.8%
Unknown	0 0%	1 3.1%	1 1.6%
Education (Count of Participants)
Less than HS	1 3.3%	0 0%	1 1.6%
HS	4 13.3%	2 6.3%	6 9.7%
Part college	3 10%	10 31.3%	13 21%
College	13 43.3%	15 46.9%	28 45.2%
Advanced	8 26.7%	4 12.5%	12 19.4%
Unknown	1 3.3%	1 3.1%	2 3.2%

Outcome Measures

1. Secondary Outcome

Title	HAM-A
Description	Hamilton Rating Scale for Anxiety (HAM-A) is a 14-item clinician-administered scale measuring symptoms with total scale from 0 (not present) to 56 (severe) to severe anxiety.
Time Frame	baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR Plus CBT	Placebo Plus CBT
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day.	matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy
Measure Participants	26	29
Baseline	16.7 (5.2)	17.8 (4.7)
LOCF (last observation carried forward)	5.9 (3.9)	9.4 (7.7)

2. Secondary Outcome

Title	Clinical Global Impression Scales for Severity and Improvement
Description	The Clinical Global Impression Scales for Severity and Improvement (CGI-I and CGI-S), both clinician rated, measures overall severity of symptoms and level of improvement on a seven-point scale from 0 (not applicable or not assessed) to 7, where 7 is the most severe. In order for a participant to be considered a treatment responder, he or she must receive a score of 1 (not ill or very much improved) or 2 (borderline mentally ill or much improved).
Time Frame	up to 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR Plus CBT	Placebo Plus CBT
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day.	matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy
Measure Participants	26	29
CGI-S Baseline	4.1 (0.5)	4.3 (0.5)
CGI-S LOCF	2.5 (1.2)	2.9 (1.2)
CGI-I Baseline	3.3 (1.6)	2.7 (1.9)
CGI-I LOCF	1.8 (1.0)	2.4 (1.1)

3. Secondary Outcome

Title	Changes in Sexual Functioning Questionnaire (CSFQ)
Description	Changes in Sexual Functioning Questionnaire (CSFQ) at week 16 as compared to baseline. The CSFQ assesses interest, functioning, and satisfaction in sex on a six-point scale, where 1 is greater than normal and 6 is totally absent, with full range from 5 (greater than normal) to 30 (totally absent).
Time Frame	baseline and week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR Plus CBT	Placebo Plus CBT
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day.	matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy
Measure Participants	26	29
Baseline	15.1 (6.3)	16.6 (5.7)
LOCF	1.8 (0.9)	14.1 (6.5)

4. Primary Outcome

Title	MADRS
Description	Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-administered, with overall score ranges from 0 (normal) to 54 (severe depression). Score at 16 weeks as compared to baseline.
Time Frame	baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR Plus CBT	Placebo Plus CBT
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day.	matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy
Measure Participants	26	29
Baseline	27.1 (5.5)	28.6 (6.5)
LOCF (last observation carried forward)	9.1 (6.9)	15.7 (11.9)

Adverse Events

Arm/Group Title	Seroquel XR Plus CBT		Placebo Plus CBT
Arm/Group Description	Participants were required to take a minimum of one 50 mg pill of quetiapine XR a day.		matching placebo pills plus 16 weeks of Cognitive Behavioral Therapy
All Cause Mortality
	Seroquel XR Plus CBT		Placebo Plus CBT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Seroquel XR Plus CBT		Placebo Plus CBT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Seroquel XR Plus CBT		Placebo Plus CBT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/26 (92.3%)		11/29 (37.9%)
Blood and lymphatic system disorders
Blood clot	1/26 (3.8%)		0/29 (0%)
Nervous system disorders
Sedation	24/26 (92.3%)		11/29 (37.9%)
Psychiatric disorders
depression	1/26 (3.8%)		0/29 (0%)

Limitations/Caveats

The limitations of this research are the small sample size and the high rate of subject drop-out between randomization and initiation of treatment.

More Information

Certain Agreements

All Principal Investigators ARE 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.