Original Research

Prazosin Outcomes in Older Veterans With Posttraumatic Stress Disorder

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

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.

Limitations and Strengths

While this study is the largest study to evaluate outcomes of prazosin in older patients with PTSD, there are several important limitations. The study population was small and all were male. The results of this study may not be applicable to women. Another limitation was several missing values in our data set, as some secondary outcomes were not collected via telephone follow-up visits. This could potentially contribute a measurement bias in the reported secondary outcomes results, specifically for the PCL-5 and ISI. Additionally, some veterans in this study may have reported symptomatic improvement based on the additional supportive intervention that clinical pharmacists were able to offer, as well as concomitant participation in psychotherapy. This may be reflected in the study results. This study did not have a true placebo group, as we may find a reduction in symptoms with placebo.

Strengths of this study include multiple data points for assessment of prazosin tolerability and a pre- and poststudy design, which allowed for the veterans to serve as their own control. Another strength of this study is that data were complete for primary outcome measures, including the CAPS Recurrent and Distressing Dreams Item, where prazosin showed significant benefit in reduction of PTSD-related nightmares. While the results of this study are reassuring, further randomized, double-blind, placebo-controlled trials are likely needed in order to establish efficacy and tolerability of prazosin in older veterans for PTSD related nightmares.

Conclusion

These results demonstrate prazosin therapy in older veterans can significantly improve PTSD-related nightmares and PTSD severity. Prazosin was well tolerated in this population at doses higher than previously reported in other studies. This study shows that prazosin therapy can be effectively managed and tolerated in older veterans with complex medical and psychiatric comorbidities to provide favorable patient outcomes.

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Iowa City VA Health Care System and by the Health Services Research and Development Service, US Department of Veterans Affairs.

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

References

Limitations and Strengths

Conclusion

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