Original Research

Prazosin Outcomes in Older Veterans With Posttraumatic Stress Disorder

Even at relatively high dosages, prazosin was well tolerated and significantly improved posttraumatic stress disorder severity and related nightmares in an older patient population.

Fed Pract. 2020 February;37(2):72-78

Author(s):

References

1. Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry. 1989;146(6):697-707.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington VA: American Psychiatric Association; 2013.

3. Southwick SM, Krystal JH, Morgan CA, et al. Abnormal noradrenergic function in posttraumatic stress disorder. Arch Gen Psychiatry. 1993;50(4):266-274.

4. Geracioti TD Jr, Baker DG, Ekhator NN, et al. CSF norepinephrine concentrations in posttraumatic stress disorder. Am J Psychiatry. 2001;158(8):1227-1230.

5. Friedman MJ. Posttraumatic and Acute Stress Disorders. 6th ed. New York: Springer Publishing; 2015.

6. Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013;170(9):1003-1010.

7. Raskind MA, Peskind ER, Hoff DJ, et al. 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;61(8):928-934.

8. Raskind MA, Peskind ER, Kanter ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160(2):371-373.

9. Germain A, Richardson R, Moul DE, et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans. J Psychosom Res. 2012;72(2):89-96.

10. Taylor HR, Freeman MK, Cates ME. Prazosin for treatment of nightmares related to posttraumatic stress disorder. Am J Health Syst Pharm. 2008;65(8):716-722.

11. 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;61(2):129-133.

12. 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;16(3):165-171.

13. Raskind MA, Peskind ER, Chow B, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378(6):507-517.

14. The Management of Posttraumatic Stress Disorder Work Group. VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. Version 3.0–2017. https://www.healthquality.va.gov/guidelines/MH/ptsd/VADoDPTSDCPGFinal.pdf. Published June 2017. Accessed January 7, 2020.

15. Nichols BL, Czirr R. 24/Post-traumatic stress disorder: hidden syndrome in elders. Clin Gerontol. 1986;5(3-4):417-433.

16. Supiano MA, Linares OA, Smith MJ, Halter JB. Age-related differences in norepinephrine kinetics: effect of posture and sodium-restricted diet. Am J Physiol. 1990;259(3, pt 1):E422-E431.

17. Raskind MA, Peskind ER, Holmes C, Goldstein DS. Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer’s disease. Biol Psychiatry. 1999;46(6):756-765.

18. Dinnen S, Simiola V, Cook JM. Post-traumatic stress disorder in older adults: a systematic review of the psychotherapy treatment literature. Aging Ment Health. 2015;19(2):144-150.

Posttraumatic stress disorder (PTSD) is a common psychiatric condition in the veteran population and is associated with significant sleep disturbances and trauma-related nightmares.¹ PTSD can present with intrusive symptoms, such as recurrent memories or dreams, which are associated with traumatic events.² Clinical studies have described an increase in central nervous system (CNS) noradrenergic activity in PTSD; specifically, noradrenergic outflow and/or postsynaptic adrenoreceptor responsiveness is increased.^3,4 Targeting a reduction in noradrenergic activity via antagonism of noradrenergic receptors has been a therapeutic treatment strategy in PTSD.

Prazosin crosses the blood-brain barrier and works to antagonize α-1 adrenoreceptors to decrease noradrenergic outflow.⁵ It has been shown in multiple trials to effectively reduce nightmares and improve sleep quality in the veteran population.^6-12 However, a recent negative trial contributed to a downgraded recommendation for prazosin in the treatment of PTSD-related nightmares in the joint PTSD guideline from the US Department of Veterans Affairs (VA) and US Department of Defense (DoD).^13,14

The diagnosis of PTSD in veterans aged ≥ 65 years has been increasing due to improved recognition.¹⁵ As a result, prazosin may be considered more frequently as a treatment option for those patients who report PTSD-related nightmares. It is important to recognize that the normal physiologic process of aging is associated with increased noradrenergic outflow, which may change the pharmacodynamics of prazosin in geriatric patients.^12,16 This may necessitate increased doses to adequately antagonize the α-1 adenoreceptor.¹⁷ High doses of prazosin may increase the risk of hypotension in older patients.¹² This increased risk is especially concerning for patients who already receive multiple medications or have comorbid conditions that impact blood pressure (BP).

The existing literature has few studies that have reported on outcomes with prazosin use in older veterans.^11,12 The few existing reports provide clinically valuable descriptions of tolerability and efficacy with prazosin. For example, Peskind and colleagues showed prazosin to be an effective agent in the treatment of PTSD-related nightmares.¹² However, in older veterans prazosin dosing > 4 mg has not been described or reported in the literature.

There appears to be a lack of clinical guidance with regards to dosing of prazosin in older patients. The goal of the current study was to assess the outcomes of older veterans with PTSD under pharmacist management of prazosin at our outpatient Prazosin Titration Clinic (PTC) in order to contribute to the minimal, yet valuable, existing clinical literature.

Methods

This study was approved by the University of Iowa Institutional Review Board and Iowa City Veterans Affairs Health Care System (ICVAHCS) research and development committee. The study was a retrospective chart review of older patients with consultations referred to the ICVAHCS PTC. To be eligible for inclusion, veterans with a PTSD diagnosis must have been evaluated at an initial consult appointment with a mental health clinical pharmacy specialist (MH CPS) from February 1, 2016 to August 31, 2018, and had at least 1 follow-up appointment. Follow-up visits were conducted either by telephone or in a face-to-face clinic visit.

References

1. Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry. 1989;146(6):697-707.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington VA: American Psychiatric Association; 2013.

3. Southwick SM, Krystal JH, Morgan CA, et al. Abnormal noradrenergic function in posttraumatic stress disorder. Arch Gen Psychiatry. 1993;50(4):266-274.

4. Geracioti TD Jr, Baker DG, Ekhator NN, et al. CSF norepinephrine concentrations in posttraumatic stress disorder. Am J Psychiatry. 2001;158(8):1227-1230.

5. Friedman MJ. Posttraumatic and Acute Stress Disorders. 6th ed. New York: Springer Publishing; 2015.

6. Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013;170(9):1003-1010.

7. Raskind MA, Peskind ER, Hoff DJ, et al. 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;61(8):928-934.

8. Raskind MA, Peskind ER, Kanter ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160(2):371-373.

9. Germain A, Richardson R, Moul DE, et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans. J Psychosom Res. 2012;72(2):89-96.

10. Taylor HR, Freeman MK, Cates ME. Prazosin for treatment of nightmares related to posttraumatic stress disorder. Am J Health Syst Pharm. 2008;65(8):716-722.

11. 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;61(2):129-133.

12. 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;16(3):165-171.

13. Raskind MA, Peskind ER, Chow B, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378(6):507-517.

14. The Management of Posttraumatic Stress Disorder Work Group. VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. Version 3.0–2017. https://www.healthquality.va.gov/guidelines/MH/ptsd/VADoDPTSDCPGFinal.pdf. Published June 2017. Accessed January 7, 2020.

15. Nichols BL, Czirr R. 24/Post-traumatic stress disorder: hidden syndrome in elders. Clin Gerontol. 1986;5(3-4):417-433.

16. Supiano MA, Linares OA, Smith MJ, Halter JB. Age-related differences in norepinephrine kinetics: effect of posture and sodium-restricted diet. Am J Physiol. 1990;259(3, pt 1):E422-E431.

17. Raskind MA, Peskind ER, Holmes C, Goldstein DS. Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer’s disease. Biol Psychiatry. 1999;46(6):756-765.

18. Dinnen S, Simiola V, Cook JM. Post-traumatic stress disorder in older adults: a systematic review of the psychotherapy treatment literature. Aging Ment Health. 2015;19(2):144-150.

Aging and Trauma: Post Traumatic Stress Disorder Among Korean War Veterans

Prazosin Outcomes in Older Veterans With Posttraumatic Stress Disorder

Even at relatively high dosages, prazosin was well tolerated and significantly improved posttraumatic stress disorder severity and related nightmares in an older patient population.

References

Methods

Pages

Next Article: