Study of the Effectiveness of Quetiapine for the Treatment of Alcohol Dependency

• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00498628
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), AstraZeneca (Industry), US Department of Veterans Affairs (U.S. Fed)
• Enrollment: 224
• Locations: 7
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 32
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether quetiapine fumarate extended release is effective in the treatment of alcohol dependence in very heavy drinkers.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism; Alcohol Abuse	Drug: Quetiapine fumarate; Other: Placebo	Phase 2

Detailed Description

This study will investigate quetiapine fumarate XR (SEROQUEL XR®), a dibenzothiazepine derivative, as a potential medication for treating alcohol dependence. The immediate release form of quetiapine fumarate, SEROQUEL XR®, is approved by the FDA for treatment of schizophrenia and acute manic episodes associated with bipolar disorder. The extended release formulation (SEROQUEL XR®) is also approved by the FDA and is undergoing clinical investigation for the treatment of major depressive disorders, schizophrenia, generalized anxiety disorder, and alcohol dependence.

Treatment with other atypical antipsychotics such as clozapine and olanzapine has resulted in decreases in alcohol use in alcohol dependent patients with and without comorbid psychiatric diagnoses. Quetiapine, like clozapine, appears to have efficacy in reducing drug and alcohol use among alcoholics and drug dependent patients with co-morbid psychiatric illness.

Study Design

• Study Type: Interventional
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-Blind, Placebo Controlled Trial to Assess the Efficacy of Quetiapine Fumarate Extended Release for the Treatment of Alcohol Dependence in Very Heavy Drinkers.
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Quetiapine fumarate plus medical management	Drug: Quetiapine fumarate; Quetiapine fumarate- taken daily, for 12 weeks; Other Names: SEROQUEL XR
Placebo Comparator: 2 Medical management plus placebo comparator	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Heavy Drinking Days [Weeks 3 - 11]

   A heavy drinking day is defined as 5 or more drinks for men and 4 or more drinks for women during a 24 hour period.

Secondary Outcome Measures

1. Percent Days Abstinent [Weeks 3-11]

   Timeline Follow-back drinking data is used to calculate the % of days abstinent per week during Weeks 3-11

2. Drinks Per Drinking Day [Study Weeks 3-11]

   Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day

3. Drinks Per Day [Study Weeks 3-11]

   Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per day

4. Percent Very Heavy Drinking Day [Study Weeks 3-11]

   Timeline Follow Back data used to calculate the % of very heavy drinking days per week. Heavy drinking is 10+ drinks per day for females and 12+ drinks per day for males

5. Percent Subjects Abstinent [Study Weeks 3-11]

   Timeline Follow Back data used to calculate the % of subjects that maintained abstinence weeks 3-11.

6. Percent Subjects With no Heavy Drinking Day [Study Weeks 3-11]

   Timeline Follow Back data used to calculate the % of subjects that didn't have a heavy drinking day during study weeks 3-11.

7. Drinking Consequences Score [Weeks 6 & 12]

   Drinkers Inventory of Consequences (DrInC) - Alcohol-related problems are determined using the DrInC (Miller et al., 1995). The DrInC is a self-administered 50-item questionnaire designed to measure adverse consequences of alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. Each scale provides a lifetime and past 3-month measure of adverse consequences, and scales can be combined to assess total adverse consequences. We used a modified version of the DrInC that just included the 45-items that summed the Interpersonal, Physical, Social, and Impulsivity items. This total score (min=0, max=135) was analyzed in this study with high scores indicative of more alcohol-related consequences (a poor outcome for a given study participant). The DrInC was assessed at study weeks 6 and 12. Analyses averaged across these weeks.

8. Penn Alcohol Craving Score (PACS_ [Weeks 4, 6, 8, 10, and 12]

   The Penn Alcohol Craving Scale (PACS) is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week (Flannery et al., 1999). The summed total score of the 5 items was used in the analysis (min=0, max=30) with higher scores indicative of higher craving for alcohol (a poor outcome). Based on clinical study results, the PACS has been shown to be a reliable and valid measure of alcohol craving and can predict subjects at risk for subsequent relapse. The PACS was assessed at study weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks.

9. Montgomery-Asberg Depression Rating Scale (MADRS) [Weeks 3-11]

   The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression (Montgomery and Asberg, 1979). The scale was constructed to be sensitive to changes in treatment effects. Its capacity to differentiate between responders and non-responders to antidepressant treatment has been shown to be comparable to the Hamilton Rating Scale for Depression, another established measure of depressive symptomatology, but the MADRS has greater sensitivity to change during the course of a depressive phase. It has exhibited high inter-rater reliability and appears to be oriented more towards psychic as opposed to somatic aspects of depression. The MADRS is the sum of the 10-item in a checklist where items are rated on a scale of 0 to 6 with anchors at 2-point intervals. Scores range from 0 to 60. Higher scores are indicative of greater depressive symptoms (a poor outcome). The MADRS was assessed at weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks.

10. Hamilton Anxiety Scale (HAM-A) [Weeks 4, 6, 8, 10, and 12]

    The Hamilton Anxiety Scale consists of 14 items, each defined by a series of symptoms. Similar to the HAM-D, each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe) (Guy, 1976). A total score is derived from the summed items (min=0, max=56) with higher scores indicative of greater anxiety (a poor outcome). The HAM-A was assessed at study weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks.

11. Pittsburgh Sleep Quality Score [Weeks 4, 8, 12]

    The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); >6 indicative of "poor" sleep quality. The PSQI was assessed at study weeks 4,8, and 12. Analyses averaged across these weeks.

12. Quality of Life SF - 12 - Mental Aggregate Score [Week 12]

    The SF-12 will be used to assess overall health status. The SF-12 is a 12-item questionnaire developed in 1994 as a shorter alternative to the SF-36 to reproduce the physical and mental health summary measures with at least 90% accuracy. We calculated the physical and mental component summary scores which were both converted to T-scores (min=0, max=100) normed to the general population such that a T=50 is the average score in the general population. Higher scores are indicative of better health status.

13. Quality of Life SF-12 - Physical Aggregate Score [Week 12]

    The SF-12 will be used to assess overall health status. The SF-12 is a 12-item questionnaire developed in 1994 as a shorter alternative to the SF-36 to reproduce the physical and mental health summary measures with at least 90% accuracy. We calculated the physical and mental component summary scores which were both converted to T-scores (min=0, max=100) normed to the general population such that a T=50 is the average score in the general population. Higher scores are indicative of better health status.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Between the ages of 18 and 65 years old

• DSM-IV diagnosis of current alcohol dependence as supported by SCID Module E

• Report "very heavy" drinking (10 or more drinks per drinking day for men or 8 or more drinks per drinking day for women) at least 40% of the days during the interval from day 31 to 90 prior to the initial screening visit (i.e. a total of 24 days of this 60-day period), with at least one day of "very heavy" drinking occurring within the last 2 weeks before screening

• Seeking treatment for alcohol dependence and desire reduction or cessation of drinking

• Able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures

• Females of child bearing potential must agree to use of at least one approved method of birth control, or must be surgically sterile or postmenopausal

• Able to take oral medication, willing to adhere to the medication regimen, and willing to return for regular visits

• Able to understand written and oral instructions in English and to complete the questionnaires required by the protocol

• Can complete all psychological assessments required at screening and baseline

• Able to provide evidence of stable residence in the last 2 months prior to randomization, have reasonable transportation arrangements to study site, and have no plans to move within the next 3 months or unresolved legal problems; must provide contact information of family member, spouse, or significant other who can contact subject in case of missed appointment

• Breath alcohol concentration (BAC) equal to 0.00 when s/he signed the informed consent document

• Must have an absolute neutrophil count of 1.5 x 109/L or greater.

Exclusion Criteria:

Please contact site for additional information.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston University School of Medicine, Psychiatry Clinical Studies Unit	Boston	Massachusetts	United States	02118
2	Dartmouth Medical School, Dept. of Psychiatry	Lebanon	New Hampshire	United States	03755
3	University of Pennsylvania, Treatment Research Center	Philadelphia	Pennsylvania	United States	19104
4	Brown University Center for Alcohol and Addiction Studies	Providence	Rhode Island	United States	12906
5	White River Junction VA Medical Center	White River Junction	Vermont	United States	05009
6	University of Virginia, Dept. of Psychiatric Medicine	Charlottesville	Virginia	United States	22908
7	University of Virginia	Richmond	Virginia	United States	23294

Sponsors and Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• National Institute on Drug Abuse (NIDA)
• AstraZeneca
• US Department of Veterans Affairs

Investigators

• Study Director: Raye Z. Litten, PhD, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Principal Investigator: Margaret E. Mattson, PhD, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Principal Investigator: Joanne Fertig, PhD, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• ClinicalTrials.gov Identifier: NCT00498628
• Other Study ID Numbers: NIAAA_DTRR-2007-LITTEN-01
• First Posted: Jul 10, 2007
• Last Update Posted: Mar 19, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by National Institute on Alcohol Abuse and Alcoholism (NIAAA): Alcoholism; Alcohol dependence; Quetiapine
• Additional relevant MeSH terms: Alcoholism; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	Interested candidates responded by telephone to advertisements at 5 academic centers in the United States between December 2007 and May 2009.
Pre-assignment Detail	218 comprises the Modified Intent To Treat group (MITT)

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Period Title: Overall Study
STARTED	105	113
COMPLETED	90	92
NOT COMPLETED	15	21

Baseline Characteristics

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management	Total
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator	Total of all reporting groups
Overall Participants	105	113	218
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	105 100%	113 100%	218 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.4 (9.3)	45.5 (9.8)	45.4 (9.4)
Sex: Female, Male (Count of Participants)
Female	17 16.2%	26 23%	43 19.7%
Male	88 83.8%	87 77%	175 80.3%
Region of Enrollment (participants) [Number]
United States	105 100%	113 100%	218 100%

Outcome Measures

1. Primary Outcome

Title	Percent Heavy Drinking Days
Description	A heavy drinking day is defined as 5 or more drinks for men and 4 or more drinks for women during a 24 hour period.
Time Frame	Weeks 3 - 11

Outcome Measure Data

Analysis Population Description

Intention to Treat

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [percentage of heavy drinking days]	37.1 (3.5)	37.9 (3.34)

2. Secondary Outcome

Title	Percent Days Abstinent
Description	Timeline Follow-back drinking data is used to calculate the % of days abstinent per week during Weeks 3-11
Time Frame	Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [percentage of days abstinent]	49.5 (3.71)	47.1 (3.54)

3. Secondary Outcome

Title	Drinks Per Drinking Day
Description	Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per drinking day
Time Frame	Study Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [drinks per drinking day]	6.2 (.47)	6.3 (.45)

4. Secondary Outcome

Title	Drinks Per Day
Description	Timeline Follow Back daily drinking data used to calculate the weekly mean drinks per day
Time Frame	Study Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [drinks per day]	4.3 (0.43)	4.4 (0.41)

5. Secondary Outcome

Title	Percent Very Heavy Drinking Day
Description	Timeline Follow Back data used to calculate the % of very heavy drinking days per week. Heavy drinking is 10+ drinks per day for females and 12+ drinks per day for males
Time Frame	Study Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [percentage heavy drinking days]	16.5 (2.56)	18.8 (2.44)

6. Secondary Outcome

Title	Percent Subjects Abstinent
Description	Timeline Follow Back data used to calculate the % of subjects that maintained abstinence weeks 3-11.
Time Frame	Study Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Count of Participants [Participants]	12 11.4%	12 10.6%

7. Secondary Outcome

Title	Percent Subjects With no Heavy Drinking Day
Description	Timeline Follow Back data used to calculate the % of subjects that didn't have a heavy drinking day during study weeks 3-11.
Time Frame	Study Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Count of Participants [Participants]	17 16.2%	24 21.2%

8. Secondary Outcome

Title	Drinking Consequences Score
Description	Drinkers Inventory of Consequences (DrInC) - Alcohol-related problems are determined using the DrInC (Miller et al., 1995). The DrInC is a self-administered 50-item questionnaire designed to measure adverse consequences of alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. Each scale provides a lifetime and past 3-month measure of adverse consequences, and scales can be combined to assess total adverse consequences. We used a modified version of the DrInC that just included the 45-items that summed the Interpersonal, Physical, Social, and Impulsivity items. This total score (min=0, max=135) was analyzed in this study with high scores indicative of more alcohol-related consequences (a poor outcome for a given study participant). The DrInC was assessed at study weeks 6 and 12. Analyses averaged across these weeks.
Time Frame	Weeks 6 & 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [score on a scale]	18.5 (1.87)	22.5 (1.78)

9. Secondary Outcome

Title	Penn Alcohol Craving Score (PACS_
Description	The Penn Alcohol Craving Scale (PACS) is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week (Flannery et al., 1999). The summed total score of the 5 items was used in the analysis (min=0, max=30) with higher scores indicative of higher craving for alcohol (a poor outcome). Based on clinical study results, the PACS has been shown to be a reliable and valid measure of alcohol craving and can predict subjects at risk for subsequent relapse. The PACS was assessed at study weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks.
Time Frame	Weeks 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Mean (Standard Error) [score on a scale]	12.1 (0.63)	12.8 (0.60)

10. Secondary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Description	The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression (Montgomery and Asberg, 1979). The scale was constructed to be sensitive to changes in treatment effects. Its capacity to differentiate between responders and non-responders to antidepressant treatment has been shown to be comparable to the Hamilton Rating Scale for Depression, another established measure of depressive symptomatology, but the MADRS has greater sensitivity to change during the course of a depressive phase. It has exhibited high inter-rater reliability and appears to be oriented more towards psychic as opposed to somatic aspects of depression. The MADRS is the sum of the 10-item in a checklist where items are rated on a scale of 0 to 6 with anchors at 2-point intervals. Scores range from 0 to 60. Higher scores are indicative of greater depressive symptoms (a poor outcome). The MADRS was assessed at weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks.
Time Frame	Weeks 3-11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [score on a scale]	2.8 (0.39)	4.1 (0.37)

11. Secondary Outcome

Title	Hamilton Anxiety Scale (HAM-A)
Description	The Hamilton Anxiety Scale consists of 14 items, each defined by a series of symptoms. Similar to the HAM-D, each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe) (Guy, 1976). A total score is derived from the summed items (min=0, max=56) with higher scores indicative of greater anxiety (a poor outcome). The HAM-A was assessed at study weeks 4, 6, 8, 10, and 12. Analyses averaged across these weeks.
Time Frame	Weeks 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [score on a scale]	2.4 (0.26)	3.0 (.24)

12. Secondary Outcome

Title	Pittsburgh Sleep Quality Score
Description	The PSQI is a 19-item questionnaire assessing the subject's overall sleep experience in the past 30 days (Buysse et al-1989). The lower the overall score, the better the person sleeps. The tool has an adequate internal reliability, validity and consistency for clinical and community samples of the various populations. Range is (0-21); >6 indicative of "poor" sleep quality. The PSQI was assessed at study weeks 4,8, and 12. Analyses averaged across these weeks.
Time Frame	Weeks 4, 8, 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [score]	4.1 (0.27)	5.1 (0.26)

13. Secondary Outcome

Title	Quality of Life SF - 12 - Mental Aggregate Score
Description	The SF-12 will be used to assess overall health status. The SF-12 is a 12-item questionnaire developed in 1994 as a shorter alternative to the SF-36 to reproduce the physical and mental health summary measures with at least 90% accuracy. We calculated the physical and mental component summary scores which were both converted to T-scores (min=0, max=100) normed to the general population such that a T=50 is the average score in the general population. Higher scores are indicative of better health status.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Quetiapine Fumerate Plus Medical Management	Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management	Medical management plus placebo comparator
Measure Participants	105	113
Least Squares Mean (Standard Error) [score on a scale]	51.5 (1.12)	50.7 (1.08)

14. Secondary Outcome

Title	Quality of Life SF-12 - Physical Aggregate Score
Description	The SF-12 will be used to assess overall health status. The SF-12 is a 12-item questionnaire developed in 1994 as a shorter alternative to the SF-36 to reproduce the physical and mental health summary measures with at least 90% accuracy. We calculated the physical and mental component summary scores which were both converted to T-scores (min=0, max=100) normed to the general population such that a T=50 is the average score in the general population. Higher scores are indicative of better health status.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Quetiapine	Placebo
Arm/Group Description	Quetiapine fumarate plus medical management Quetiapine fumarate: Quetiapine fumarate- taken daily, for 12 weeks	Medical management plus placebo comparator Placebo: Placebo
Measure Participants	105	113
Least Squares Mean (Standard Error) [score on a scale]	51.0 (0.82)	50.6 (0.93)

Adverse Events

Adverse Event Reporting Description	Systematic assessment at each clinic visit and telephone contact in response to the question "How have you been feeling since the last time we spoke?"
Arm/Group Title	Quetiapine Fumerate Plus Medical Management		Sugar Pill Plus Medical Management
Arm/Group Description	Quetiapine fumarate - target dose 400mg/day plus medical management		Medical management plus placebo comparator
All Cause Mortality
	Quetiapine Fumerate Plus Medical Management		Sugar Pill Plus Medical Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Quetiapine Fumerate Plus Medical Management		Sugar Pill Plus Medical Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/105 (5.7%)		5/113 (4.4%)
Blood and lymphatic system disorders
Ruptured Spleen	1/105 (1%)	1	0/113 (0%)	0
Cardiac disorders
Pre-ventricular contractions	0/105 (0%)	0	1/113 (0.9%)	1
Injury, poisoning and procedural complications
Automobile Accident	1/105 (1%)	1	0/113 (0%)	0
Psychiatric disorders
Alcohol Detoxification	3/105 (2.9%)	4	3/113 (2.7%)	3
Behavioral Disturbance while intoxicated	0/105 (0%)	0	1/113 (0.9%)	1
Suicidal Ideation	1/105 (1%)	1	0/113 (0%)	0
Other (Not Including Serious) Adverse Events
	Quetiapine Fumerate Plus Medical Management		Sugar Pill Plus Medical Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/105 (100%)		110/113 (97.3%)
Gastrointestinal disorders
Dry Mouth	34/105 (32.4%)	36	10/113 (8.8%)	11
Dyspepsia	14/105 (13.3%)	22	2/113 (1.8%)	2
Nausea	10/105 (9.5%)	11	20/113 (17.7%)	25
Vomiting	15/105 (14.3%)	20	14/113 (12.4%)	15
Constipation	8/105 (7.6%)	10	8/113 (7.1%)	11
Diarrhoea	6/105 (5.7%)	7	11/113 (9.7%)	12
General disorders
Fatigue	22/105 (21%)	29	17/113 (15%)	18
Feeling Abnormal	10/105 (9.5%)	11	8/113 (7.1%)	8
Irritability	8/105 (7.6%)	8	7/113 (6.2%)	9
Pain	6/105 (5.7%)	6	9/113 (8%)	9
Infections and infestations
Upper Respiratory Tract Infection	4/105 (3.8%)	4	12/113 (10.6%)	12
Investigations
Weight Increased	20/105 (19%)	21	12/113 (10.6%)	13
Blood Glucose Increased	3/105 (2.9%)	3	8/113 (7.1%)	9
Metabolism and nutrition disorders
Increased Appetite	12/105 (11.4%)	12	1/113 (0.9%)	1
Musculoskeletal and connective tissue disorders
Back Pain	8/105 (7.6%)	10	15/113 (13.3%)	22
Arthralgia	9/105 (8.6%)	12	5/113 (4.4%)	6
Mylagia	6/105 (5.7%)	6	4/113 (3.5%)	4
Nervous system disorders
Dizziness	15/105 (14.3%)	20	5/113 (4.4%)	6
Sedation	16/105 (15.2%)	18	3/113 (2.7%)	3
Somnelence	36/105 (34.3%)	42	10/113 (8.8%)	10
Headache	36/105 (34.3%)	60	49/113 (43.4%)	83
Tremor	16/105 (15.2%)	19	14/113 (12.4%)	18
Psychiatric disorders
Anxiety	20/105 (19%)	26	25/113 (22.1%)	33
Insomnia	14/105 (13.3%)	15	24/113 (21.2%)	26
Depressed Mood	7/105 (6.7%)	8	10/113 (8.8%)	13
Abnormal Dreams	10/105 (9.5%)	10	8/113 (7.1%)	10
Agitation	10/105 (9.5%)	11	6/113 (5.3%)	8
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	11/105 (10.5%)	14	11/113 (9.7%)	13
Cough	8/105 (7.6%)	10	13/113 (11.5%)	14
Oropharynageal Pain	9/105 (8.6%)	10	6/113 (5.3%)	7
Skin and subcutaneous tissue disorders
Hyperhidrosis	7/105 (6.7%)	7	7/113 (6.2%)	7

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.