PTSD Treatment if Prazosin fails: Doxazosin

There is evidence that doxazosin may be an effective alternative to prazosin in the treatment of posttraumatic stress disorder (PTSD) related intrusive nightmares and flashbacks symptoms.
Which of the following features separates doxazosin from prazosin?

Prazosin is used for treatment of intrusive nightmares and flashbacks symptoms of PTSD.

 

Prazosin has limitation in some patients due to:

  • Need for multiple dosings in 24 hour period: due to short half life of 2-3 hours with duration of action of 6-10 hours.
  • Effect wearing off during later part of night due to short duration of action.
  • Increased risk of hypotension.

If patient is not tolerating prazosin, you can consider doxazosin as an alternative medication to target intrusive nightmares symptoms of PTSD.

DOXAZOSIN

  • Prazosin and doxazosin are both α1-adrenergic antagonists.
  • FDA approved for hypertension and benign prostatic hyperplasia.
  • ==> Not approved for PTSD (off label use).
  • In contrast to Prazosin, Doxazosin have half life of 16-30 hr and hence can be taken as once daily dosing.
  • The risk of hypotension is low due to better absorption profile of doxazosin.
  • The slower onset of action also reduces the risk of first-dose postural hypotension as compared to prazosin.
  • The controlled-release gastrointestinal therapeutic system (GITS) is also available as XL formulation and this can controls fluctuations in plasma drug levels.

Doxazosin Dosage:

  • Initiate at 1 mg daily and titrate to 4-8 mg/day (based on toleration and response).
  • Can be given at any time of the day as AM or HS dosing, with or without food.
  • Doxazosin extended release [XL] GITS formulation: initiating dose is 4 mg daily and titrate to 16 mg daily over 2 weeks (based on toleration and response).

This dose recommendation is based on following studies:

  • 4 mg/day for 8 weeks resulted in improved sleep quality, decreased frequency and intensity of trauma-related nightmares, and improved ability to function during the daytime. (2)
  • 4-8 mg/day was effective in 12 week open label study with 12 participants. (4)
  • Doxazosin extended release [XL] GITS titrated from 4 mg daily to 16 mg daily over the course of 12 days resulted in significant improvement in a double-blind, placebo-controlled study in 8 participants. (5)

Case reports showing efficacy of Doxazosin for PTSD nightmares:

  • Patient #1: Doxazosin 1 mg dosing improved nightmares in 1 week but no improvement in sleep.
  • Patient #2: Doxazosin 2 mg dosing improved nightmares and sleep.
  • Patient #3: Doxazosin 1 mg dosing improved nightmares in 2 weeks.

Read reference 6 (pdf)

Important clinical fact:

Doxazosin is used for erectile dysfunctions due to it’s effect on vasodilation and enhancing blood flow to the area. This makes Doxazosin a good option for PTSD patient with underlying sexual dysfunction.

References:
  1. Psychiatr Ann. 2016; 46(9): 553–555.
  2. Prim Care Companion CNS Disord. 2012; 14(5): PCC.12l01356.
  3. BJU Int. 2006 Mar; 97(3):559-66.
  4. J Clin Psychopharmacol. 2010 Feb; 30(1):84-5.
  5. J Clin Psychiatry. 2016 May; 77(5):e561-5.
  6. Braz J Psychiatry. 2019 Mar-Apr;41(2):189-190.
INTERESTED IN LEARNING MORE?
READ THE FOLLOWING COURSE CHAPTER SERIES FOR MORE DETAILS:

Trauma and Stress Related Disorders: PTSD

(1) VA/DOD Clinical Practice Guidelines for PTSD and Acute Stress Disorder. (Read Chapter)

(2) Prazosin: Dosing & Side Effects Knowledge. (Read Chapter)

(3) Prazosin: High dose for resistant PTSD nightmares. (Read Chapter)

(4) Medication Options if Prazosin Fails: Doxazosin. (Read Chapter)

(5) Medication Options if Prazosin Fails: Alpha 2 Adrenergic Receptor Agonists. (Read Chapter)

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