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#384 Treatment of PTSD Nightmares: Is prazosin a dream come true?


CLINICAL QUESTION
QUESTION CLINIQUE
 How effective is prazosin for nightmares in posttraumatic stress disorder (PTSD)?

BOTTOM LINE
RÉSULTAT FINAL
 In patients with PTSD, prazosin may decrease nightmare symptoms by 1-3 points (0-8 scale), but does not consistently improve sleep quality compared to placebo over 6-26 weeks. When titrated gradually, prazosin is well-tolerated but more experience dry mouth (16% versus 4%) and dizziness (47% versus 39%) compared to placebo.


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EVIDENCE
DONNÉES PROBANTES
  • Results statistically significant unless stated.
  • 7 systematic reviews (5-11 Randomized Controlled Trials [RCTs], 441-796 patients)1-7 over the past 5 years evaluated prazosin versus placebo. At 6-26 weeks:
    • Nightmares:
      • 7 systematic reviews: all showed statistically significant improvements using different measures.
        • Example: distressing dreams score (0 to 8 points, lower is better;8 baseline ~6):
          • RCTs:8-14 4/7 prazosin better by 1.5 to 2.9 points, 3/7 no difference.
    • Sleep quality:
      • 5 systematic reviews: 3 showed statistically significant improvements, 2 did not.
        • Example: Most commonly used sleep quality score (0 to 21 points, lower is better; baseline ~11-15; clinically meaningful change: 2.5-3 points):15,16
          • RCTs:8,9,11-13,17,18 4/7 prazosin better by 2.4 to 4.9 points, 3/7 no difference.
    • Adverse events:
      • Discontinuations due to adverse events: not reported.
      • Dry mouth:66% versus 4.0% (placebo), number needed to harm (NNH)=8; Dizziness:6 46.4% versus 38.8% (placebo), NNH=13.
  • Limitations: Differences in patients enrolled (example: mild PTSD to suicidal patients), outcomes assessed, drop-out rates (range 0-70%), and size of treatment effect. Largest RCT performed in patients with clinically stable PTSD showed no differences.8
CONTEXT
CONTEXTE
  • Trauma-related nightmares reported by 80% with PTSD in first 3 months, with symptoms resolving in about half of patients several months later.3,20
  • RCT dosing: prazosin 1mg at bedtime titrated every few days or every week to minimize adverse events, particularly orthostatic hypotension.8-14,17,18 Mean RCT doses ~5-15mg per day (at bedtime or divided).
  • Guidelines suggest:
    • In addition to trauma-focused cognitive behavioural therapy (CBT) for general PTSD treatment (strong recommendation),19,21 some recommend specific forms of CBT (example: image rehearsal therapy)20 for those with PTSD-associated nightmares.
    • Prazosin may be used for treatment of PTSD-associated nightmares (weak recommendation).19,20

Dennis Neufeld March 4, 2025

Prazosin is not very effective for treating PTSD nightmares.

Huda Alzubaidi March 12, 2025

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Author(s)
Auteur(s)
  • Scott Thomas PharmD candidate
  • Matthew Exner PharmD candidate
  • Michael R Kolber MD CCFP MSc
  • Jamie Falk PharmD

1. Lappas AS, Glarou E, Polyzopoulou ZA, et al. J Sleep Med. 2024 Jul:119:467-479.

2. Skeie-Larsen M, Stave R, Grønli J, et al. Int J Environ Res Public Health. 2022 Dec 31;20(1):777.

3. Zhang Y, Vitiello MV, Yang L, et al. Neurosci. Biobehav Rev. 2022 Aug;139:10417.

4. Reist C, Streja E, Tang CC, et al. CNS Spectr. 2021 Aug;26(4):338-344.

5. Yücel DE, van Emmerik AAP, Souama C, et al. Sleep Med Rev. 2020 Apr;50:101248.

6. Zhang Y, Ren Rong, Sanford LD, et al. Sleep Med. 2020 Mar;67:225-231.

7. Huang C-Y, Zhao Y-F, Zhang Z-X, et al. Ann Med 2024 Dec;56:1 (2381696).

8. Raskind MA, Peskind ER, Chow B, et al. N Engl J Med 2018 Feb 8;378(6):507-517.

9. Petrakis IL, Desai N, Gueorguieva R, et al. Alcohol Clin Exp Res. 2016 Jan;40(1):178-186.

10. Raskind MA, Peskind ER, Kanter ED, et al. Am J Psychiatry. 2003 Feb;160(2):371-373.

11. Raskind MA, Peskind ER, Hoff DJ, et al. Biol Psychiatry. 2007 Apr 15;61(8):928-934.

12. Raskind MA, Peterson K, WIlliams T, et al. Am J Psychiatry. 2013 Sept;170(9):1003-1010.

13. NCT00202449. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/study/NCT00202449. Accessed: December 4, 2024.

14. Taylor FB, Martin P, Thompson C, et al. Biol Psychiatry. 2008 Mar 15;63(6):629–632.

15. Park BK. Child Health Nurs Res. 2020 Jan;26(1):55-63.

16. Qin, Z., Zhu, Y., Shi, DD. et al. BMC Med Res Methodol 2024 Aug 8;24(1):177.

17. Ahmadpanah M, Sabzeiee P, Hosseini S, et al. Neuropsychobiology. 2014;69(4):235-242.

18. Germain A, Richardson R, Moul DE, et al. J Psychosom Res. 2012 Feb;72(2):89-96.

19. VA/DoD Clinical practice guideline for management of posttraumatic stress disorder and acute stress disorder 2023. Available at: https://www.healthquality.va.gov/guidelines/MH/ptsd/VA-DOD-CPG-PTSD-Provider-Summary.pdf Accessed: December 4, 2024.

20. Morgenthaler TI, Auerbach S, Casey KR, et al. J Clin Sleep Med. 2018 Jun 15;14(6):1041–1055.

21. Post-traumatic stress disorder. National Institute for Health and Care Excellence. Available at: https://www.nice.org.uk/guidance/ng116/resources/posttraumatic-stress-disorder-pdf-66141601777861. Accessed: December 4, 2024.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.