Prazosin for Treating Noncombat Trauma Post-Traumatic Stress Disorder

Post-Traumatic Stress Disorder Clinical Trial

Official title:

Prazosin for Noncombat Trauma PTSD

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00183430
• Other study ID #: R01MH069867
• Secondary ID: R01MH069867DATR
• Status: Terminated
• Phase: N/A
• Start date: October 2003
• Est. completion date: December 2010

Study information

• Verified date: June 2018
• Source: Seattle Institute for Biomedical and Clinical Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: December 2010
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Disease
• Post-Traumatic Stress Disorder
• Sleep Initiation and Maintenance Disorders
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Drug:
• Prazosin
Prazosin capsules 1 to 25 mg are taken orally twice per day in divided doses at 10 am and bedtime.
• Placebo
Placebo capsules are taken orally twice per day at 10 am and bedtime.

Behavioral:
• Psychotherapy
All participants will undergo psychotherapy during medication treatment period.

Locations

Country	Name	City	State
United States	VA Puget Sound Health Care System	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Seattle Institute for Biomedical and Clinical Research	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Peskind ER, Bonner LT, Hoff DJ, Raskind MA. Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder. J Geriatr Psychiatry Neurol. 2003 Sep;16(3):165-71. — View Citation

Raskind MA, Dobie DJ, Kanter ED, Petrie EC, Thompson CE, Peskind ER. The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: a report of 4 cases. J Clin Psychiatry. 2000 Feb;61(2):129-33. — View Citation

Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, Shofer J, O'Connell J, Taylor F, Gross C, Rohde K, McFall ME. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007 Apr 15;61(8):928-34. Epub 2006 Oct 25. — View Citation

Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Tröster K, Thomas RG, McFall MM. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003 Feb;160(2):371-3. — View Citation

Raskind MA, Thompson C, Petrie EC, Dobie DJ, Rein RJ, Hoff DJ, McFall ME, Peskind ER. Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder. J Clin Psychiatry. 2002 Jul;63(7):565-8. — View Citation

Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, Peskind ER, Raskind MA. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008 Mar 15;63(6):629-32. Epub 2007 Sep 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline to Week 8
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.	Baseline to Week 8
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.	Baseline to Week 8