Savvy Psychopharmacology

PTSD nightmares: Prazosin and atypical antipsychotics

Current Psychiatry. 2012 June;11(6):59-67

References

1. Dohrenwend BP, Turner JB, Turse NA, et al. The psychological risks of Vietnam for U.S. veterans: a revisit with new data and methods. Science. 2006;313(5789):979-982.

2. Tanielian T, Jaycox L. eds. Invisible wounds of war: psychological and cognitive injuries, their consequences, and services to assist recovery. Santa Monica, CA: RAND Corporation; 2008.

3. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington DC: American Psychiatric Association; 2000.

4. Wittmann L, Schredl M, Kramer M. Dreaming in posttraumatic stress disorder: a critical review of phenomenology psychophysiology and treatment. Psychother Psychosom. 2007;76(1):25-39.

5. Clum GA, Nishith P, Resick PA. Trauma-related sleep disturbance and self-reported physical health symptoms in treatment-seeking female rape victims. J Nerv Ment Dis. 2001;189(9):618-622.

6. Kramer TL, Booth BM, Han X, et al. Service utilization and outcomes in medically ill veterans with posttraumatic stress and depressive disorders. J Trauma Stress. 2003;16(3):211-219.

7. Neylan TC, Marmar CR, Metzler TJ, et al. Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans. Am J Psychiatry. 1998;155(7):929-933.

8. Nappi CM, Drummond SP, Hall JM. Treating nightmares and insomnia in posttraumatic stress disorder: a review of current evidence. Neuropharmacology. 2012;62(2):576-585.

9. Maher MJ, Rego SA, Asnis GM. Sleep disturbances in patients with post-traumatic stress disorder: epidemiology impact and approaches to management. CNS Drugs. 2006;20(7):567-590.

10. van Liempt S, Vermetten E, Geuze E, et al. Pharmacotherapy for disordered sleep in post-traumatic stress disorder: a systematic review. Int Clin Psychopharmacol. 2006;21(4):193-202.

11. Aurora RN, Zak RS, Auerbach SH, et al. Best practice guide for the treatment of nightmare disorder in adults. J Clin Sleep Med. 2010;6(4):389-401.

12. Boehnlein JK, Kinzie JD. Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin. J Psychiatr Pract. 2007;13(2):72-78.

13. Strawn JR, Geracioti TD, Jr. Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depress Anxiety. 2008;25(3):260-271.

14. Calohan J, Peterson K, Peskind ER, et al. Prazosin treatment of trauma nightmares and sleep disturbance in soldiers deployed in Iraq. J Trauma Stress. 2010;23(5):645-648.

15. Daly CM, Doyle ME, Radkind M, et al. Clinical case series: the use of Prazosin for combat-related recurrent nightmares among Operation Iraqi Freedom combat veterans. Mil Med. 2005;170(6):513-515.

16. Peskind ER, Bonner LT, Hoff DJ, et al. Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder. J Geriatr Psychiatry Neurol. 2003;16(3):165-171.

17. Raskind MA, Dobie DJ, Kanter ED, et al. 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.

18. Taylor F, Raskind MA. The alpha1-adrenergic antagonist prazosin improves sleep and nightmares in civilian trauma posttraumatic stress disorder. J Clin Psychopharmacol. 2002;22(1):82-85.

19. Raskind MA, Thompson C, Petrie EC, et al. Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder. J Clin Psychiatry. 2002;63(7):565-568.

20. 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.

21. 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.

22. Taylor FB, Martin P, Thompson C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008;63(6):629-632.

23. Byers MG, Allison KM, Wendel CS, et al. Prazosin versus quetiapine for nighttime posttraumatic stress disorder symptoms in veterans: an assessment of long-term comparative effectiveness and safety. J Clin Psychopharmacol. 2010;30(3):225-229.

24. Jin H, Lanouette NM, Mudaliar S, et al. Association of posttraumatic stress disorder with increased prevalence of metabolic syndrome. J Clin Psychopharmacol. 2009;29(3):210-215.

25. Cates ME, Jackson CW, Feldman JM, et al. Metabolic consequences of using low-dose quetiapine for insomnia in psychiatric patients. Community Ment Health J. 2009;45(4):251-254.

26. Williams SG, Alinejad NA, Williams JA, et al. Statistically significant increase in weight caused by low-dose quetiapine. Pharmacotherapy. 2010;30(10):1011-1015.

27. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry. 2004;65(2):267-272.

Table 3

Recommended medication treatments for PTSD-associated nightmares

Evidence level	Medication	Evidence
Recommended for treating PTSD-associated nightmares
1, 4	Prazosin	In 3 level 1 studies, adding prazosin (mean dose 3 mg/d) significantly decreased trauma-related nightmares according to the CAPS “recurrent distressing dreams” item after 3 to 9 weeks of treatment vs placebo in veteran and civilian patients (N = 57)
Not suggested for treating PTSD-associated nightmares
1	Venlafaxine	No difference between extended-release venlafaxine (37.5 to 300 mg/d) and placebo in the CAPS-SX₁₇ “distressing dreams” item at 12 weeks in 340 PTSD patients
May be considered for treating PTSD-associated nightmares
4	Clonidine	Reduced the number of nightmares in 11 of 13 refugees for 2 weeks to 3 months (dose: 0.2 to 0.6 mg/d)
May be considered for treating PTSD-associated nightmares, but data are low grade and sparse
4	Trazodone	Although trazodone (25 to 600 mg) significantly decreased nightmare frequency in veteran patients during an 8-week hospital stay (N = 60), 19% discontinued therapy because of side effects
4	Olanzapine	Adjunctive olanzapine (10 to 20 mg) rapidly improved sleep in a case series of combat-related PTSD patients resistant to SSRIs and benzodiazepines (N = 5)
4	Risperidone	In case series, risperidone (0.5 to 3 mg) significantly decreased CAPS scores for recurrent distressing dreams and proportion of traumatic dreams documented in diaries of combat veterans over 6 weeks (N = 17), and improved nightmares in adult burn patients taking pain medications after 1 to 2 days (N = 10)
4	Aripiprazole	In a case series, aripiprazole (15 to 30 mg at bedtime) with CBT or sertraline significantly improved nightmares in 4 of 5 combat-related PTSD patients
4	Topiramate	Topiramate reduced nightmares in 79% of civilians with PTSD and fully suppressed nightmares in 50% of patients in a case series (N = 35)
4	Low-dose cortisol	Significant decrease in frequency but not intensity of nightmares with low-dose cortisol (10 mg/d) in civilians with PTSD (N = 3)
4	Fluvoxamine	In 2 case series, fluvoxamine (up to 300 mg/d) significantly decreased the IES-R level of “dreams about combat trauma” but not the SRRS “bad dreams” rating at 10 weeks (N = 21). During 4 to 12 weeks of follow-up there was a qualitative decrease in reported nightmares in veteran patients (n = 12)
2	Triazolam/nitrazepam	Limited data showed triazolam (0.5 mg) and nitrazepam (5 mg) provide equal efficacy in decreasing the number of patients who experience unpleasant dreams over 1 night
4	Phenelzine	One study showed phenelzine monotherapy (30 to 90 mg) resulted in elimination of nightmares within 1 month (N = 5); another reported “moderately reduced traumatic dreams” (N = 21) in veterans. Therapy was discontinued because of short-lived efficacy or plateau effect
4	Gabapentin	Adjunctive gabapentin (300 to 3,600 mg/d) improved insomnia and decreased nightmare frequency and/or intensity over 1 to 36 months in 30 veterans with PTSD
4	Cyproheptadine	Conflicting data ranges from eliminating nightmares to no changes in the presence or intensity of nightmares
4	TCAs	Among 10 Cambodian concentration camp survivors treated with TCAs, 4 reported their nightmares ceased and 4 reported improvement after 1-year follow-up
4	Nefazodone	Reduced nightmare occurrence in 3 open-label studies as monotherapy (386 to 600 mg/d). Not recommended first line because of hepatotoxicity risk
No recommendation because of sparse data
2	Clonazepam	Clonazepam (1 to 2 mg/d) was ineffective in decreasing frequency or intensity of combat-related PTSD nightmares in veterans (N = 6)
Evidence levels: High-quality randomized clinical trials with narrow confidence intervals Low-quality randomized clinical trials or high-quality cohort studies Case-control studies Case series; poor case-control studies; poor cohort studies; case reports
CAPS: Clinician-Administered PTSD Scale; CAPS-SX₁₇: 17-item Clinician-Administered PTSD Scale; CBT: cognitive-behavioral therapy; IES-R: Impact of Event Scale-Revised; PTSD: posttraumatic stress disorder; SRRS: Stress Response Rating Scale; SSRI: selective serotonin reuptake inhibitor; TCAs: tricyclic antidepressants Source: Adapted from Aurora RN, Zak RS, Auerbach SH, et al. Best practice guide for the treatment of nightmare disorder in adults. J Clin Sleep Med. 2010;6(4):389-401

CASE CONTINUED: Medication change, improvement

After reviewing AASM’s treatment recommendations, we prescribe prazosin, 1 mg at bedtime for 7 nights, then increase by 1 mg at bedtime each week until Mr. S’s nightmares improve. He reports a substantial improvement in nightmare severity and frequency after a few weeks of treatment with prazosin, 5 mg at bedtime.

Prazosin

Clinical Point

Prazosin reduced trauma nightmares and improved sleep quality and global clinical status more than placebo

Prazosin is an α1-adrenergic receptor antagonist with good CNS penetrability. The rationale for reducing adrenergic activity to address intrusive PTSD symptoms has been well documented.^12,13 In open-label trials,^14-18 a chart review,¹⁹ and placebo-controlled trials,^20-22prazosin reduced trauma nightmares and improved sleep quality and global clinical status more than placebo (Table 4). In these studies, prazosin doses ranged from 1 to 20 mg/d, with an average of 3 mg at bedtime and a starting dose of 1 mg. Prazosin is the only agent recommended in the AASM’s Best Practice Guide for treating PTSD-related nightmares.¹¹