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Doxazosin for PTSD, and does it slow biologic aging?

Updated: May 9

Doxazosin (CARDURA)

Pronunciation: dox AY zo sin / car DUR ah

Mascot / Mnemonic: “Carder, Dox A’s or sin” 

Mechanism: Alpha-1 antagonist

doxazosin for PTSD nightmares mechanism

FDA-approved for:

 ❖ Hypertension

 ❖ Benign prostatic hyperplasia (BPH)

Used off-label for:

 ❖ Nephrolithiasis

 ❖ PTSD nightmares

 ❖ PTSD hyperarousal and flashbacks 

Doxazosin (Cardura) has been considered as an alternative to prazosin for off-label treatment of PTSD nightmares.

Compared to prazosin, doxazosin has a longer half-life,  slower peak plasma levels, and lower incidence of orthostatic hypotension (Regan K et al, APA Annual Meeting, 2024).  The duration of action of prazosin is 6–8 hours, which may be too short to prevent early morning nightmares. 

Doxazosin is associated with decelerated biological aging in humans and a causal role in longevity was confirmed in a model organism—extending lifespan of C. elegans worms by 15% (McIntyre & Rahman et al, 2021). Other drugs with alpha-1 blocking activity that increased C. elegans lifespan include loxapine (antipsychotic, 43% increase), promethazine (antiemetic, 32%), mianserin (antidepressant available in Europe, 32%), thioridazine (antipsychotic, 31%), and nortriptyline (TCA, 21%) (Xiaolan et al, 2013).

The extended release formulation of doxazosin (Cardura XL), approved only for BPH, has fewer side effects: dizziness 5% ER (versus 9% with IR) and postural hypotension 1.2% (versus 2.2% with IR). Unfortunately the ER formulation is relatively expensive, even with GoodRx. 

Even the IR formulation of doxazosin is more expensive than prazosin but it can be obtained for $16 with GoodRx at some pharmacies. Doxazosin is about $100 out of pocket without GoodRx.

Doxazosin can improve erectile dysfunction, as it causes vasodilation and enhances blood flow to the area (Kaplan et al, 2006). Concomitant use of doxazosin with a phosphodiesterase-5 (PDE-5) inhibitor like sildenafil can result in additive blood pressure lowering effects and symptomatic hypotension. 

Dynamic interactions:

 ❖ Hypotensive effects

      ➤ Caution with PDE-5 inhibitors

      ➤ Caution with other alpha blocking medications (those psychotropics that must be titrated slowly like quetiapine, clozapine, iloperidone, trazodone, TCAs)

Kinetic interactions:

 ❖ CYP3A4 substrate (fish)

doxazosin interactions CYP3A4

doxazosin pill pictures and chemical structure

Doxazosin dosing:

For hypertension, start 1 mg QD, then may double dose q 1–2 wk up to Max of 16 mg QD.  For BPH, maintenance dose is 1–8 mg QD.  For PTSD, start 1 mg HS. 

The ER formulation for BPH is started at 4 mg ER QD with breakfast, with max of 8 mg QD. 

Alpha blocks Alpha noradrenergic receptor antagonists most prescribed tamsulosin, terazosin, prazosin, doxazosin, alfuzosin

Copyright 2024, CaferMed Publishing

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