ALPHABLOCKER COMBINATION THERAPY IN PTSD AND BPH RECOMMENDATIONS

ALPHABLOCKER COMBINATION THERAPY IN PTSD AND BPH RECOMMENDATIONS






Alpha-Blocker Combination Therapy in PTSD and BPH

Recommendations for Use

June 2012

VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives

The following recommendations are based on medical evidence, clinician input, and expert opinion. The content of the document is dynamic and will be revised as new information becomes available. The purpose of this document is to assist practitioners in clinical decision-making, to standardize and improve the quality of patient care, and to promote cost-effective drug prescribing. The clinician should utilize this guidance and interpret it in the clinical context of the individual patient. Individual cases that are outside the recommendations should be adjudicated at the local facility according to the policy and procedures of its P&T Committee and Pharmacy Services.

The product information should be consulted for detailed prescribing information.

Issue

A question commonly asked in VA is: when is the use of two alpha1 blockers (α1-blocker) appropriate for male Veterans with diagnoses of posttraumatic stress disorder (PTSD) and benign prostatic hyperplasia (BPH)?


Background


The prescribing of more than one α1-blocker is not uncommon among Veterans. Analysis of the period of December 2011 through February 2012 identified 1543 Veterans with concurrent filling of prescriptions for prazosin plus at least one other α1-blocker (Table 1). Approximately 35% had both PTSD and BPH listed as a diagnosis. The combination of prazosin with another α1-blocker that is not considered clinically uroselective was also a common occurrence.


Table 1 Concurrent Filling of Prazosin plus Another α1-blocker by Selected Diagnoses

Diagnosis/Rx*^

Prazosin +

Any other a-blocker , n (%)

Prazosin + 1 a-blocker

Prazosin + 2 a-blockers

Alfuzosin

Doxazosin

Tamsulosin

Terazosin

BPH-alone

114 (7.39)

0

9

68

36

1

PTSD-alone

714 (46.27)

1

62

325

322

4

BPH + PTSD

534 (34.61)

4

37

30

187

3

Neither

181 (11.73)

-

-

-

-

-

Total

1543






*Diagnosis/Rx = Diagnosis of BPH/PTSD on at least 1 inpatient or 2 outpatient diagnoses with 24 months prior to Rx initiation.

^Active Rx between 12/1/2011 – 2/29/2012 and concomitant Rx overlapping >=30 days


Prazosin’s label indication is for the treatment of hypertension. Frequent off-label uses include BPH and PTSD associated nightmares.


Veterans with a diagnosis of PTSD that includes nightmares are recommended to have a trial of prazosin (VA/DoD PTSD Clinical Practice Guideline1). Prazosin is the only α1-blocker studied as a treatment for PTSD and hypothesized to be the only one sufficiently lipophilic to penetrate the CNS.2 The target dose is 6 to 10 mg/day.1


Prazosin is not recommended as a treatment for BPH by the American Urological Association.3 However, several controlled clinical trials are available on the use of prazosin as a treatment for BPH in doses ranging from 1 to 9 mg/day with 2 mg twice a day being most common.4-13


Recommendations

  1. When PTSD with nightmares and BPH co-exist and a α1-blocker is indicated, prazosin should be the initial agent tried and its dose titrated to one that improves both conditions and is tolerated.

  2. When PTSD nightmares respond to a lower dose of prazosin, but BPH requires a higher dose that is not tolerated, then the dose of prazosin should be lowered to what was effective for PTSD and an alternative treatment be considered for the remaining BPH symptoms.

    1. Adjustment of the dose of other drugs that lower blood pressure may be needed to increase the tolerability of prazosin.

    2. One alternative would be the addition of a clinically uroselective α1-blocker (e.g., VA National Formulary tamsulosin 0.4 mg daily). Adjustment of the dose of other drugs that lower blood pressure may be needed to increase the tolerability of the combination α1-blockers.

    3. Patients unable to tolerate or who find the combination of prazosin and a clinically uroselective α1-blocker ineffective for their BPH symptoms should remain on prazosin at the dose effective for PTSD- related nightmares and be considered for an alternative BPH treatment such as finasteride or referral to urology.

    4. Although not specifically studied, the combination of prazosin and another α1-blocker that is not considered clinically uroselective is not recommended due the likelihood of increased adverse events.

  3. Patients with existing BPH being treated with a α1-blocker other than prazosin who have PTSD-related nightmares should be considered for a trial of prazosin monotherapy.

    1. As in the previous example (#2), the combination of prazosin with a clinically uroselective α1-blocker may be considered when prazosin alone is effective in reducing or eliminating PTSD-related nightmares, but ineffective for BPH symptoms or is intolerable.

  4. Patients whose PTSD-related nightmares do not respond to prazosin or who cannot tolerate prazosin should be referred for other PTSD treatments and their BPH managed with a different α1-blocker on VA National Formulary.

  5. The combination of more than one α1-blocker, other than prazosin and a clinically uroselective α1-blocker, in Veterans with PTSD and BPH (or other conditions where a α1-blocker may be considered e.g., hypertension, heart failure) does not appear warranted and should be adjudicated locally.


References


  1. Department of Veterans Affairs and Department of Defense Clinical Practice Guidelines for Management of Post-Traumatic Stress Disorder, Version 2.0, 2010. Office of Quality and Safety, VA, Washington, DC and Quality Management Division, United States Army MEDCOM. Access at www.healthquality.va.gov, May 29, 2012.

  2. Miller LJ. Prazosin for the treatment of posttraumatic stress disorder sleep disturbance. Pharmacotherapy 2008;28(5):656-666.

  3. Tsujii T. Comparison of prazosin, terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia: a short-term open, randomized multicenter study. BPH Medical Therapy Study Group. Benign prostatic hyperplasia. Int J Urol 2000;7:199-205.

  4. American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (BPH), revised 2010, page 10. Accessed at http://www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines.cfm?sub=bph, May 30, 2012.

  5. Buzelin JM, Hebert M, Blondin P. Alpha-blocking treatment with alfuzosin in symptomatic benign prostatic hyperplasia: comparative study with prazosin. The PRAZALF Group. Br J Urol 1993;72:922-7.

  6. Steven ID, Coffey GA, Graham NM, Wlodarczyk J, Curtis P. The effect of prazosin on patients with symptoms of benign prostatic hypertrophy. Aust Fam Physician 1993;22:1260-4.

  7. Chapple CR, Stott M, Abrams PH, Christmas TJ, Milroy EJ. A 12-week placebo-controlled double-blind study of prazosin in the treatment of prostatic obstruction due to benign prostatic hyperplasia. Br J Urol 1992;70:285-94.

  8. Ruutu ML, Hansson E, Juusela HE, et al. Efficacy and side-effects of prazosin as a symptomatic treatment of benign prostatic obstruction. Scand J Urol Nephrol 1991;25:15-9.

  9. Le Duc A, Cariou G, Baron C, et al. A multicenter, double-blind, placebo-controlled trial of the efficacy of prazosin in the treatment of dysuria associated with benign prostatic hypertrophy. Urol Int 1990;45 (Suppl 1):56-62.

  10. Chapple CR, Christmas TJ, Milroy EJ. A twelve-week placebo-controlled study of prazosin in the treatment of prostatic obstruction. Urol Int 1990;45 (Suppl 1):47-55.

  11. Milroy E. Clinical overview of prazosin in the treatment of prostatic obstruction. Urol Int 1990;45 (Suppl 1):1-3.

  12. Kirby RS, Coppinger SW, Corcoran MO, et al. Prazosin in the treatment of prostatic obstruction. A placebo-controlled study. Br J Urol 1987;60:136-42.

  13. Hedlund H, Andersson KE, Ek A. Effects of prazosin in patients with benign prostatic obstruction. J Urol 1983;130:275-8.



Prepared by Elaine Furmaga, PharmD, Mark Geraci, PharmD and Todd Semla, PharmD

PBM Contact: Todd Semla, PharmD


3

Updated version may be found at www.pbm.va.gov or vaww.pbm.va.gov





Tags: therapy, alphablocker, combination, recommendations