Clincosm LogoSign in Get a demo

Quetiapine Augmentation for Treatment-resistant PTSD

Sponsor
VA Office of Research and Development (U.S. Fed)
Overall Status
Completed
CT.gov ID
NCT00292370
Collaborator
AstraZeneca (Industry)
124
Enrollment
3
Locations
3
Arms
40
Duration (Months)
41.3
Patients Per Site
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the response of veterans with PTSD without an optimal response to paroxetine to quetiapine augmentation versus placebo.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

This is a two-site study designed to evaluate the efficacy and safety of quetiapine augmentation of paroxetine treatment in veterans with PTSD who have failed to respond to paroxetine treatment.

In Phase I, eligible patients will take open-label paroxetine (up to 60 mg daily) for 8 weeks. Patients who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for the second phase. In Phase II, patients will continue taking open-label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) or placebo for 8 weeks in a double-blind fashion.

Study Design

Study Type:
Interventional
Actual Enrollment :
124 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Placebo-controlled Trial of Adjunctive Quetiapine for Refractory PTSD
Study Start Date :
Jan 1, 2006
Actual Primary Completion Date :
Dec 1, 2008
Actual Study Completion Date :
May 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Other: Arm 1: Open Label (OL) Paroxetine

Open-label Paroxetine In Phase I, eligible participants will take open-label (OL) Paroxetine (up to 60 mg) daily for 8 weeks. Participants who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for Phase II.

Drug: Open Label (OL) Paroxetine
Open-label Paroxetine
Other Names:
  • Paxil

    		•
    Placebo Comparator: Arm 2 OL Paroxetine + DB Placebo

    In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion.

    Drug: Open Label (OL) Paroxetine
    Open-label Paroxetine
    Other Names:
  • Paxil

    • Drug: Placebo
    Double-blind placebo taken with OL paroxetine
    Other Names:
  • sugar pill

    		•
    Experimental: Arm 3: OL Paroxetine + DB Quetiapine

    In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion.

    Drug: Open Label (OL) Paroxetine
    Open-label Paroxetine
    Other Names:
  • Paxil

    • Drug: Quetiapine
    Double-blind quetiapine taken with OL paroxetine
    Other Names:
  • Seroquel

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Clinician-Administered PTSD Scale for DSM-IV Total Score. [From baseline (week 8) to endpoint (week 16 or termination)]

      The Clinician-Administered PTSD Scale for DSM-IV (CAPS) is described in the National Center for PTSD Instruction Manual (November 2000) as a semi-structured clinical interview designed to assess the seventeen symptoms for Post Traumatic Stress Disorder (PTSD) outlined in the DSM-IV, along with five associated features. Ratings are made on a 5 point continuum from the lowest frequency or intensity to the highest. Total CAPS score is a summed score that ranges from 0 to 136 where 0 is asymptomatic and higher scores equal more severe PTSD symptomatology. Also, a change in total CAPS score of 15 points was proposed as clinically significant change.

    Secondary Outcome Measures

    1. Change in CGI-I [From Baseline (week 8) to Endpoint (week 16 or termination)]

      Clinical Global Impressions Scale and Global Improvement Subscales (CGI-I) is a 7-point scale which was used to assess overall improvement. The scores range from 1 to 7, with 1 indicating very much improved and 7 indicating very much worse.

    2. Change in Mean PANSS Total and Subscores From Baseline to Endpoint [Baseline (week 8) to Endpoint (week 16 or termination)]

      Positive and Negative Symptom Scale (PANSS). A 30-item clinician administered rating scale for which positive, negative and general subscales are scored from 30 to 210 with a higher scores indicating greater severity of symptoms.

    3. Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores [From Baseline (week 8) to Endpoint (week 16 or Termination)]

      Hamilton Rating Scale for Depression (HAMD) was used as a measure of depression. Scoring is based on a 17-item scale. Eight items are scored on a 5 point scale from 0= not present to 4= severe. The scoring is based on the first 17 items. Scores of 0-7 normal, 8-13 is mild depression, 14-18 moderate depression, 19-22 severe depression and 23 and above very severe depression; the maximum score being 52 on the 17-point scale.

    4. Change in Total Mean Davidson Trauma Scale (DTS) [From Baseline (week 8) to Endpoint (week 16 or Termination)]

      The DTS is a 17-item self-rated scale that measures the frequency and the severity of DSM-IV PTSD symptoms. Items are rated on 5-point frequency (0 = "not at all" to 4 = "every day") and severity scales (0 = "not at all distressing" to 4 = "extremely distressing"). The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). A higher score indicates higher frequency and severity. It can be used to make a preliminary determination about whether the symptoms meet DSM criteria for PTSD. Scores can also be calculated for each of the 3 PTSD symptom clusters (i.e., B, C, and D).

    5. Change in Mean Q-LES-Q Score From Baseline to Endpoint. [From Baseline (week 8) to Endpoint (week 16 or termination)]

      Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) a self-rated 14-item questionnaire designed to assess the degree of enjoyment and satisfaction of various aspects of daily functioning. Each question is rated on a 5-point scale with scores ranging from "1 = very poor" to "5 = very good". The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70. A lower score indicates worsening and a higher score indicates better quality of life.

    6. Change in Mean Scores of Pittsburgh Sleep Quality Index (PSQI) From Baseline to Endpoint. [From Baseline (week 8) to Endpoint (week 16)]

      The PSQI is one of the most frequently used self-rated sleep questionnaire. Total score ranging from 0 to 21. Higher scores are representing worse sleep quality.

    7. Change in Mean Sheehan Disability Scale (SDS) Scores From Baseline to Endpoint. [Baseline (week 8) to Endpoint (week 16 or termination)]

      The SDS is a brief 3-item questionnaire that was used as a self-report to assess the degree to which psychiatric symptoms have disrupted the patient's work, family/home responsibilities, and social life. Score ranging from 0 (no impairment) to 30 (most severe).

    8. Change in Arizona Sexual Experience Scale (ASEX) [From Baseline (week 8) to Endpoint (week 16 or termination)]

      The ASEX is a brief 5-item rating scale that assesses five global aspects of sexual dysfunction. Score is 5 and the maximum score is 30. Lower scores indicate more positive sexual experiences.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Veteran age 18 to 75.

    • Competent to give informed consent.

    • Meeting DSM-IV criteria for PTSD.

    • Minimal CAPS score of 50 at baseline.

    • If female of childbearing potential, patient must have a negative pregnancy test and, if sexually active, be using a medically approved contraceptive method.

    • Patients who have not taken psychiatric medications within 1 week prior to study entry (except fluoxetine [5 weeks])

    • monoamine oxidase inhibitors (MAOIs [4 weeks])

    • depot neuroleptics [4 weeks])

    • or any investigational drug within 30 days prior to study enrollment.

    • To be eligible for Phase II

    • patients must be refractory to paroxetine in Phase I, as defined by less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8

    • must have PTSD symptoms at least moderate severity on CGI-S

    • and must have been compliant with study medicine in Phase I, as defined by taking at least 80% of prescribed doses.

    Exclusion Criteria:

    • History of sensitivity to paroxetine or quetiapine.

    • Failure to respond to a prior adequate therapeutic trial i.e. minimum of 8 weeks at maximum tolerated dose of paroxetine (up to 60 mg daily) or quetiapine (up to 800 mg daily).

    • Women who are

    • breast-feeding

    • pregnant

    • expect to become pregnant during the course of the study

    • or are sexually active and are not using a medically acceptable method of birth control.

    • Presence of clinically significant hepatic

    • cardiovascular

    • or other medical conditions that may prevent safe administration of paroxetine or quetiapine

    • or any other clinically significant unstable medical conditions.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham VA Medical Center Birmingham Alabama United States 35233
    2 Tuscaloosa VAMC Tuscaloosa Alabama United States 35404
    3 Ralph H. Johnson Charleston South Carolina United States 29401-5799

    Sponsors and Collaborators

    • VA Office of Research and Development
    • AstraZeneca

    Investigators

    • Principal Investigator: Mark B Hamner, MD BS, Ralph H. Johnson VA Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    VA Office of Research and Development
    ClinicalTrials.gov Identifier:
    NCT00292370
    Other Study ID Numbers:
    • CLIN-006-04F
    First Posted:
    Feb 15, 2006
    Last Update Posted:
    Oct 16, 2019
    Last Verified:
    Sep 1, 2019
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by VA Office of Research and Development
    Atypical Antipsychotics
    Controlled Trial
    Paroxetine
    Quetiapine
    Stress Disorders, Post-Traumatic
    Treatment refractory
    Treatment resistant
    Additional relevant MeSH terms:
    Disease
    Stress Disorders, Traumatic
    Stress Disorders, Post-Traumatic
    Combat Disorders
    Quetiapine Fumarate
    Paroxetine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm 1/Open-Label (OL) Paroxetine Arm 2/OL Paroxetine & Double-blind Placebo Arm 3/OL Paroxetine & Double-blind Quetiapine
    Arm/Group Description Phase I : Open-label Paroxetine In Phase I, eligible participants will take open-label (OL) paroxetine (up to 60 mg daily) for 8 weeks. Participants who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for Phase II Phase II : Double-blind placebo In Phase II, participants will continue taking open-label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind fashion. Phase II : Double-blind quetiapine In Phase II, participants will continue taking open-label paroxetine and will be randomized to the addition of quetiapine for 8 weeks in a double-blind fashion.
    Period Title: Phase I - Open-Label Paroxetine (OLP)
    STARTED 124 0 0
    COMPLETED 78 0 0
    NOT COMPLETED 46 0 0
    Period Title: Phase I - Open-Label Paroxetine (OLP)
    STARTED 0 25 25
    COMPLETED 0 21 18
    NOT COMPLETED 0 4 7

    Baseline Characteristics

    Arm/Group Title Arm 1/Open-Label (OL) Paroxetine Arm 2/OL Paroxetine & Double-blind Placebo Arm 3/OL Paroxetine & Double-blind Quetiapine Total
    Arm/Group Description Phase I : Open-label Paroxetine In Phase I, eligible participants will take open-label (OL) paroxetine (up to 60 mg daily) for 8 weeks. Participants who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS score of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for Phase II Phase II: Double-blind placebo In Phase II, participants will continue taking open-label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind fashion. Phase II: Double-blind quetiapine In Phase II, participants will continue taking open-label paroxetine and will be randomized to the addition of quetiapine in a double-blind fashion. Total of all reporting groups
    Overall Participants 124 25 25 174
    Age, Customized (years) [Mean (Standard Deviation) ]
    Age - OL Paroxetine
    52.32
    (13.23)
    NA
    (NA)
    NA
    (NA)
    52.32
    (13.23)
    Age - Double Blind
    NA
    (NA)
    57.17
    (8.74)
    54.45
    (13.69)
    54.76
    (11.48)
    Sex/Gender, Customized (Count of Participants)
    Gender OL Females
    5
    4%
    5
    20%
    Gender OL Males
    119
    96%
    119
    476%
    Sex/Gender, Customized (Count of Participants)
    Females Double Blind
    0
    0%
    1
    4%
    1
    4%
    2
    1.1%
    Males Double Blind
    0
    0%
    24
    96%
    24
    96%
    48
    27.6%
    Race/Ethnicity, Customized (Count of Participants)
    OL Amer Indian/ Alask Native
    2
    1.6%
    2
    8%
    OL African American
    50
    40.3%
    50
    200%
    OL White
    68
    54.8%
    68
    272%
    OL Unknown or Not Reported
    4
    3.2%
    4
    16%
    Race/Ethnicity, Customized (Count of Participants)
    DB Amer Indian/ Alaska Native
    0
    0%
    0
    0%
    0
    0%
    DB African American
    15
    12.1%
    10
    40%
    25
    100%
    DB White
    9
    7.3%
    14
    56%
    23
    92%
    DB Unknown/ Not Reported
    1
    0.8%
    1
    4%
    2
    8%
    Region of Enrollment (Count of Participants)
    United States
    124
    100%
    124
    496%
    Years of Education (years) [Mean (Standard Deviation) ]
    Education - Open Label (OL) Population
    13.12
    (2.05)
    NA
    (NA)
    NA
    (NA)
    13.12
    (2.05)
    Education - Double Blind (DB), Phase II
    NA
    (NA)
    13.22
    (2.74)
    12.55
    (1.53)
    12.89
    (2.24)

    Outcome Measures

    1. Primary Outcome
    Title Change in Clinician-Administered PTSD Scale for DSM-IV Total Score.
    Description The Clinician-Administered PTSD Scale for DSM-IV (CAPS) is described in the National Center for PTSD Instruction Manual (November 2000) as a semi-structured clinical interview designed to assess the seventeen symptoms for Post Traumatic Stress Disorder (PTSD) outlined in the DSM-IV, along with five associated features. Ratings are made on a 5 point continuum from the lowest frequency or intensity to the highest. Total CAPS score is a summed score that ranges from 0 to 136 where 0 is asymptomatic and higher scores equal more severe PTSD symptomatology. Also, a change in total CAPS score of 15 points was proposed as clinically significant change.
    Time Frame From baseline (week 8) to endpoint (week 16 or termination)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    CAPS Total Baseline
    72.15
    (15.96)
    68.78
    (17.01)
    CAPS Total Endpoint
    67.90
    (14.90)
    51.52
    (19.68)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 2 OL Paroxetine + DB Placebo, Arm 3: OL Paroxetine + DB Quetiapine
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Mixed Models Analysis
    Comments
    2. Secondary Outcome
    Title Change in CGI-I
    Description Clinical Global Impressions Scale and Global Improvement Subscales (CGI-I) is a 7-point scale which was used to assess overall improvement. The scores range from 1 to 7, with 1 indicating very much improved and 7 indicating very much worse.
    Time Frame From Baseline (week 8) to Endpoint (week 16 or termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with CGI-I score
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline CGI-I
    3.56
    (.85)
    3.36
    (.88)
    Endpoint CGI-I
    2.61
    (.79)
    2.22
    (1.19)
    3. Secondary Outcome
    Title Change in Mean PANSS Total and Subscores From Baseline to Endpoint
    Description Positive and Negative Symptom Scale (PANSS). A 30-item clinician administered rating scale for which positive, negative and general subscales are scored from 30 to 210 with a higher scores indicating greater severity of symptoms.
    Time Frame Baseline (week 8) to Endpoint (week 16 or termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with a PANSS score
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline Total PANSS
    46.63
    (10.13)
    47.76
    (11.09)
    Endpoint Total PANSS
    43.92
    (6.81)
    42.24
    (8.07)
    4. Secondary Outcome
    Title Change in Total Mean Hamilton Rating Scale for Depression (HAMD) Scores
    Description Hamilton Rating Scale for Depression (HAMD) was used as a measure of depression. Scoring is based on a 17-item scale. Eight items are scored on a 5 point scale from 0= not present to 4= severe. The scoring is based on the first 17 items. Scores of 0-7 normal, 8-13 is mild depression, 14-18 moderate depression, 19-22 severe depression and 23 and above very severe depression; the maximum score being 52 on the 17-point scale.
    Time Frame From Baseline (week 8) to Endpoint (week 16 or Termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with a HAMD score.
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline HAMD
    14.60
    (5.45)
    13.84
    (6.05)
    Endpoint HAMD
    12.29
    (6.35)
    9.29
    (4.56)
    5. Secondary Outcome
    Title Change in Total Mean Davidson Trauma Scale (DTS)
    Description The DTS is a 17-item self-rated scale that measures the frequency and the severity of DSM-IV PTSD symptoms. Items are rated on 5-point frequency (0 = "not at all" to 4 = "every day") and severity scales (0 = "not at all distressing" to 4 = "extremely distressing"). The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). A higher score indicates higher frequency and severity. It can be used to make a preliminary determination about whether the symptoms meet DSM criteria for PTSD. Scores can also be calculated for each of the 3 PTSD symptom clusters (i.e., B, C, and D).
    Time Frame From Baseline (week 8) to Endpoint (week 16 or Termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with a DTS score
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline DTS
    82.19
    (24.60)
    77.25
    (25.94)
    Endpoint DTS
    84.06
    (21.92)
    61.50
    (18.20)
    6. Secondary Outcome
    Title Change in Mean Q-LES-Q Score From Baseline to Endpoint.
    Description Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) a self-rated 14-item questionnaire designed to assess the degree of enjoyment and satisfaction of various aspects of daily functioning. Each question is rated on a 5-point scale with scores ranging from "1 = very poor" to "5 = very good". The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70. A lower score indicates worsening and a higher score indicates better quality of life.
    Time Frame From Baseline (week 8) to Endpoint (week 16 or termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with a Q-LES-Q score.
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline Q-LES-Q
    37.85
    (7.78)
    40.44
    (8.82)
    Endpoint Q-LES-Q
    38.22
    (6.62)
    41.06
    (6.70)
    7. Secondary Outcome
    Title Change in Mean Scores of Pittsburgh Sleep Quality Index (PSQI) From Baseline to Endpoint.
    Description The PSQI is one of the most frequently used self-rated sleep questionnaire. Total score ranging from 0 to 21. Higher scores are representing worse sleep quality.
    Time Frame From Baseline (week 8) to Endpoint (week 16)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with a PSQI score.
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline PSQI
    11.60
    (3.93)
    12.69
    (3.46)
    Endpoint PSQI
    8.70
    (3.15)
    13.19
    (2.88)
    8. Secondary Outcome
    Title Change in Mean Sheehan Disability Scale (SDS) Scores From Baseline to Endpoint.
    Description The SDS is a brief 3-item questionnaire that was used as a self-report to assess the degree to which psychiatric symptoms have disrupted the patient's work, family/home responsibilities, and social life. Score ranging from 0 (no impairment) to 30 (most severe).
    Time Frame Baseline (week 8) to Endpoint (week 16 or termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with an SDS score
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline SDS-WS
    5.07
    (3.45)
    4.44
    (2.95)
    Endpoint SDS-WS
    4.58
    (2.99)
    4.66
    (2.34)
    Baseline SDS-SL
    6.67
    (2.44)
    5.64
    (2.93)
    Endpoint SDS-SL
    5.92
    (2.55)
    4.95
    (1.83)
    Baseline SDS-FL
    5.85
    (2.92)
    4.72
    (2.48)
    Endpoint SDS-FL
    5.39
    (2.48)
    4.61
    (2.27)
    9. Secondary Outcome
    Title Change in Arizona Sexual Experience Scale (ASEX)
    Description The ASEX is a brief 5-item rating scale that assesses five global aspects of sexual dysfunction. Score is 5 and the maximum score is 30. Lower scores indicate more positive sexual experiences.
    Time Frame From Baseline (week 8) to Endpoint (week 16 or termination)

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with an ASEX score.
    Arm/Group Title Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    Measure Participants 25 25
    Baseline ASEX
    22.00
    (6.68)
    17.88
    (5.33)
    Endpoint ASEX
    21.93
    (7.45)
    16.94
    (5.84)

    Adverse Events

    Time Frame Collected over 4 months per subject.
    Adverse Event Reporting Description Collected by open-ended questions, vitals, standardized report form, and chart review at visits every two weeks, as well as by lab assessments between phases I and II.
    Arm/Group Title Arm 1: Open Label (OL) Paroxetine Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Arm/Group Description In Phase I, eligible participants will take open-label (OL) Paroxetine (up to 60 mg) daily for 8 weeks. Participants who are refractory (less than 30% reduction in CAPS scores or a minimum CAPS of 50 at week 8) and have PTSD symptoms of at least moderate severity on CGI-S will be eligible for Phase II. Open Label (OL) Paroxetine: Open-label Paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of placebo for 8 weeks in a double-blind (DB) fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Placebo: Double-blind placebo taken with OL paroxetine In Phase II, participants will continue taking open label paroxetine and will be randomized to the addition of quetiapine (up to 800 mg daily) for 8 weeks in a double blind fashion. Open Label (OL) Paroxetine: Open-label Paroxetine Quetiapine: Double-blind quetiapine taken with OL paroxetine
    All Cause Mortality
    Arm 1: Open Label (OL) Paroxetine Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm 1: Open Label (OL) Paroxetine Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/124 (4%) 0/25 (0%) 2/25 (8%)
    Cardiac disorders
    Hypotension 2/124 (1.6%) 2 0/25 (0%) 0 1/25 (4%) 1
    Hospitalized - scheduled cardiac stint 2/124 (1.6%) 2 0/25 (0%) 0 0/25 (0%) 0
    Psychiatric disorders
    Hospitalized - Suicide Ideation 1/124 (0.8%) 1 0/25 (0%) 0 0/25 (0%) 0
    Skin and subcutaneous tissue disorders
    cellulitis 0/124 (0%) 0 0/25 (0%) 0 1/25 (4%) 1
    Other (Not Including Serious) Adverse Events
    Arm 1: Open Label (OL) Paroxetine Arm 2 OL Paroxetine + DB Placebo Arm 3: OL Paroxetine + DB Quetiapine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/124 (18.5%) 2/25 (8%) 8/25 (32%)
    Cardiac disorders
    Heart palpitation 0/124 (0%) 0 0/25 (0%) 0 2/25 (8%) 2
    Nervous system disorders
    Sedation 7/124 (5.6%) 7 1/25 (4%) 1 3/25 (12%) 3
    Dizziness 6/124 (4.8%) 6 0/25 (0%) 0 0/25 (0%) 0
    Psychiatric disorders
    Confusion 0/124 (0%) 0 0/25 (0%) 0 2/25 (8%) 2
    Reproductive system and breast disorders
    Sexual Side effects 10/124 (8.1%) 10 1/25 (4%) 1 1/25 (4%) 1

    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.

    Results Point of Contact

    Name/Title Mark Hamner, MD
    Organization Ralph H. Johnson VA Medical Center
    Phone 843-789-7799
    Email Mark.Hamner@va.gov
    Responsible Party:
    VA Office of Research and Development
    ClinicalTrials.gov Identifier:
    NCT00292370
    Other Study ID Numbers:
    • CLIN-006-04F
    First Posted:
    Feb 15, 2006
    Last Update Posted:
    Oct 16, 2019
    Last Verified:
    Sep 1, 2019