Post-Traumatic Stress Disorder, Sleep Initiation and Maintenance Disorders
Conditions
Keywords
Prazosin, Sleep Disorders
Brief summary
This study will evaluate the effectiveness of prazosin in treating post-traumatic stress disorder caused by noncombat trauma in individuals taking selective serotonin reuptake inhibitors.
Detailed description
Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after exposure to a terrifying event in which grave physical harm occurred or was threatened. People with PTSD have persistent frightening thoughts and memories of their past ordeal and often feel emotionally numb, especially with people to whom they were once close. PTSD was first recognized in male combat veterans. Today, however, the majority of people who have PTSD are young women who have experienced non combat-related trauma, such as sexual or physical assault or a life-threatening illness or accident. The disorder can be short-lived, but PTSD can also become chronic, with long lasting symptoms that are often treatment-resistant, possibly causing severe functional disability. Frequent trauma-related nightmares and other debilitating sleep disruptions are examples of chronic PTSD symptoms for which an effective treatment has not been developed. Sertraline and paroxetine, both selective serotonin reuptake inhibitors (SSRIs), are the only drugs approved by the FDA for treating PTSD. Neither of them, however, has been effective in reducing PTSD-related sleep disruption. Studies have shown that the drug prazosin has been effective in reducing distressing trauma-related nightmares in older male combat veterans. This study will evaluate the effectiveness of prazosin in treating post-traumatic stress disorder caused by noncombat trauma in individuals already being treated with SSRIs. Participants in this double-blind study will first undergo 12 weeks of treatment with psychotherapy and a standard SSRI. After 12 weeks, participants will be randomly assigned to receive either prazosin or placebo in addition to psychotherapy and standard SSRI treatment for a total of 8 weeks. Study visits will occur weekly for the first 12 weeks, and then at Weeks 1, 2, 4, 6, and 8 during the 8-week phase. Additionally, follow-up visits will be held 4 and 18 weeks post-intervention. PTSD symptoms, disorder severity, and frequency of sleep disturbances will be assessed.
Interventions
DRUGPrazosin
Prazosin capsules 1 to 25 mg are taken orally twice per day in divided doses at 10 am and bedtime.
DRUGPlacebo
Placebo capsules are taken orally twice per day at 10 am and bedtime.
BEHAVIORALPsychotherapy
All participants will undergo psychotherapy during medication treatment period.
Sponsors
National Institute of Mental Health (NIMH)
Seattle Institute for Biomedical and Clinical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of PTSD, as derived from the Clinician-Administered PTSD Scale (CAPS) * Stabilized on any necessary medications for at least 4 weeks prior to study entry * Score of greater than 4 on the CAPS Recurrent Distressing Dreams item (maximum score of 8) * Score of greater than 4 on the CAPS Difficulty Falling or Staying Asleep item (maximum score of 8) * Agrees to use an effective form of contraception throughout the study
Exclusion criteria
* Any acute or significant chronic medical illness * Any unstable medical condition * Unstable angina, recent heart attack, history of congestive heart failure, pre-existing hypotension (systolic blood pressure less than 110 mm Hg), or orthostatic hypotension * Insulin-dependent diabetes * Chronic kidney or liver failure * Pancreatitis or gout * Meniere's disease, benign positional vertigo, or narcolepsy * Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist * Currently taking another alpha-1 antagonist agent * Pregnant * DSM-IV diagnosis of cognitive disorder, schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic disorder * Current delirium * Active substance dependence disorder within 3 months of study entry * Current substance use other than alcohol (no more than 2 drinks per day) * Severe psychiatric instability or situational life crises, including evidence of suicidal or homicidal ideation * Currently taking any other psychotropic medication (e.g., antidepressants, benzodiazepines, anti-convulsants, anti-psychotics, sedating antihistamines, sedatives/hypnotics (exclusionary medications will be discontinued and participants will undergo a 2-week washout period before baseline assessments)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Change | Baseline to Week 8 | The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The Clinical Global Impression of Change is used to determine the impact of treatment effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measure evaluates change from Baseline to Week 8. |
| Change in Recurring Distressing Dreams and Difficulty Falling and Staying Asleep Items of the CAPS | Baseline to Week 8 | Item B-2 recurrent distressing dreams of the event is a single item from teh Clinician Administered PTSD Scale (CAPS). The rating consists of two parts: Frequency plus Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. The total minimum score = zero. The total maximum score = 8. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 8. |
| Change in Sleep Assessed by the Pittsburgh Sleep Quality Index | Baseline to Week 8 | Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 8. |
Countries
United States
Participant flow
Recruitment details
Recruitment was conducted from April 2002 through July 2008. Participants were recruited from VA outpatient clinics and flyers in the community.
Pre-assignment details
no significant events.
Participants by arm
| Arm | Count |
|---|---|
| Prazosin Participants will receive treatment with prazosin plus psychotherapy
Prazosin : Prazosin capsules 1 to 25 mg are taken orally twice per day in divided doses at 10 am and bedtime.
Psychotherapy : All participants will undergo psychotherapy during medication treatment period. | 9 |
| Placebo Participants will receive treatment with placebo plus psychotherapy
Placebo : Placebo capsules are taken orally twice per day at 10 am and bedtime.
Psychotherapy : All participants will undergo psychotherapy during medication treatment period. | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | did not meet inclusion criteria | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Prazosin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 9 Participants | 20 Participants |
| Age, Continuous | 46 years STANDARD_DEVIATION 9.4 | 42 years STANDARD_DEVIATION 11.6 | 44 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment United States | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 8 / 11 |
| serious Total, serious adverse events | 0 / 3 | 0 / 11 |
Outcome results
Primary
Change in Recurring Distressing Dreams and Difficulty Falling and Staying Asleep Items of the CAPS
Item B-2 recurrent distressing dreams of the event is a single item from teh Clinician Administered PTSD Scale (CAPS). The rating consists of two parts: Frequency plus Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. The total minimum score = zero. The total maximum score = 8. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 8.
Time frame: Baseline to Week 8
Population: Number of participants analyzed equals the number of participants who were able to complete this assessment at Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Change in Recurring Distressing Dreams and Difficulty Falling and Staying Asleep Items of the CAPS | -2.00 Units on a Scale | Standard Deviation 0.82 |
| Placebo | Change in Recurring Distressing Dreams and Difficulty Falling and Staying Asleep Items of the CAPS | -1.09 Units on a Scale | Standard Deviation 1.93 |
Primary
Change in Sleep Assessed by the Pittsburgh Sleep Quality Index
Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 8.
Time frame: Baseline to Week 8
Population: Number of participants analyzed equals the number of participants who were able to complete this assessment at Week 8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Change in Sleep Assessed by the Pittsburgh Sleep Quality Index | 4 Units on a Scale | Standard Deviation 0.82 |
| Placebo | Change in Sleep Assessed by the Pittsburgh Sleep Quality Index | 2.09 Units on a Scale | Standard Deviation 4.42 |
Primary
Clinical Global Impression of Change
The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The Clinical Global Impression of Change is used to determine the impact of treatment effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measure evaluates change from Baseline to Week 8.
Time frame: Baseline to Week 8
Population: Number of participants analyzed equals the number of participants who were able to complete this assessment at Week 8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Clinical Global Impression of Change | 2.33 Units on a Scale | Standard Deviation 0.58 |
| Placebo | Clinical Global Impression of Change | 3.27 Units on a Scale | Standard Deviation 0.9 |