PTSD Medication Option 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?

 


 

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

 

Prazosin has limitation in some patients due to:

(a) Need for multiple doings in 24 hour period, due to short half life of 2-3 hours with duration of action of 6-10 hours.

(b) Effect wearing off during later part of night due to short duration of action.

(c) Increased risk of hypotension.

 


MECHANISM OF RESPONSE:

Patients with PTSD have increased α-adrenergic activity which affects the prefrontal cortex. This is likely responsible for exaggerated fear response. Hence α1-adrenergic antagonists have therapeutic benefit in PTSD.

 


 

If patient is not tolerating prazosin, we can try doxazosin as an alternative medication to target intrusive nightmares symptoms of PTSD. This next part of post will focus on this.

 


DOXAZOSIN:

 

Prazosin and doxazosin are both α1-adrenergic antagonists.

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 controlled-release gastrointestinal therapeutic system (GITS) is also available as XL formulation and this can controls fluctuations in plasma drug levels.

 


DOSAGE:

    • Initiate at 1 mg daily and titrate to 4-8 mg/day (based on toleration and response).

    • Can be given as AM or HS dosing.

  • 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)


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.


Source:

    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.

Please do post your questions or comments below. 


Dr. Harvinder Singh

Admin, Psychiatry Education Forum

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Responses

  1. This is extremely helpful information. I have a young woman, an Iragi refugee with significant flashbacks and has only been able to tolerate 5 mg or prazosin at night only for nightmares and that is insufficient for good control of the nighmares.

    1. Thanks Kathleen. Let us know if your patient responds positively to Doxazosin.
      Also studies have shown that high doses (>25 mg) of Prazosin is needed for treatment resistance PTSD. This dose differs by age and gender. I will try to post more details on this topics soon.
      The other option is trial of Alpha 2 Adrenergic Receptor Agonists like clonidine.

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