June 24, 2015 BlogInadequate Trials of Prazosin: Potential Missed Opportunities for Veterans With PTSD

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Nancy C. Bernardy, PhD, and Matthew J. Friedman, MD, PhD

Iowa City VA Health Care System, Iowa City, Iowa; Veterans Affairs Medical Center, White River Junction, Vermont (Drs Bernardy and Friedman)


The 2010 VA/DoD Clinical Practice Guideline recommends that clinicians consider the use of prazosin, an alpha 1 adrenergic receptor antagonist used to treat hypertension, for PTSD-related nightmares. Sleep problems are common in PTSD and may be a core feature. Research has suggested that, although prazosin has been steadily disseminated in the VA, it still may be underutilized and underdosed. In our recent study, we examined a cohort of veterans with PTSD initiating prazosin to characterize their dosing patterns and duration of use.

Administrative data identified veterans with PTSD according to ICD-9 codes. Prazosin use following initiation utilized refill data, and prazosin doses were calculated based upon total milligrams and day’s supply dispensed.

A total of 12,844 veterans with PTSD were new prazosin users during 2010. On average, the patients were 53 years of age, 92% male, and taking 6 medications at the time of prazosin initiation.

Prazosin doses generally increased during treatment, reaching an average maximum dose of 3.6 mg/d. However, only 14% reached the minimum guideline-recommended dose of 6 mg/d for an adequate trial.

Regarding duration of use, 20% of the patients never refilled their initial prazosin prescription, and 18% discontinued within 6 months. The remaining 61% took prazosin for more than 6 months, with 38% of the total sample persisting for at least 1 year. Patients with concurrent SSRI/SNRI antidepressants were more likely to maintain prazosin treatment for a year compared to non-antidepressant users. Additionally, one-year users were older and had more concurrent medications.

Recent work by Murray A. Raskind, MD, and colleagues has noted that pretreatment physiological parameters such as blood pressure in patients with PTSD may serve as a clinically useful biomarker for helping to predict the response to prazosin. Patients who had higher baseline blood pressure and smaller baseline blood pressure drop (standing for 2 minutes for supine) showed substantially greater PTSD symptom improvement associated with prazosin treatment. Although preliminary, these findings suggest that increased peripheral noradrenergic tone is a potential biomarker for a clinically therapeutic response to prazosin in PTSD, and they may also account for varied findings using prazosin for nightmares.

Although large pharmacy databases are very useful for addressing some questions, they cannot answer others. In the present case, we don’t know why the drug was discontinued after one year in two-thirds of the patients. Was it because patients and/or providers found it ineffective at lower doses? Was it because of side effects? Was it because prescribers did not titrate the dose to optimal levels to achieve full symptom response?

Our findings justify further investigation to identify factors related to the common failure to reach recommended prazosin dosage guidelines for PTSD-related nightmares. The answer to this question and others would provide clinicians who treat patients with PTSD a vital opportunity for more optimal use of this low-cost, guideline-recommended treatment.


Raskind MA, Peskind ER, Millard S, et al. Baseline blood pressure is associated with PTSD symptom response to prazosin in active duty combat soldiers. Poster presented at: 53rd Annual American College of Neuropsychopharmacology Meeting; December 9, 2014; Phoenix, AZ.

Financial disclosure:Drs Bernardy and Friedman had no relevant personal financial relationships to report.

Category: PTSD , Veteran
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6 thoughts on “ BlogInadequate Trials of Prazosin: Potential Missed Opportunities for Veterans With PTSD

  1. Any idea when Raskind, et. al. plan to publish their very large negative trial of prazosin for PTSD? They posted the negative results on almost a year ago, yet no publication. I’d be happy if it works, but these results suggest otherwise:
  2. What about continuing trazadone, anti depressants and adding prazosin? I see to many medications being added to patients with out proper evaluation of the combined affects…thoughts?
  3. We also eagerly await the results of Dr. Raskind’s trial. Until a peer-reviewed publication becomes available, it is impossible to conduct a thorough critique of the merits and limitations of that study. It is important to recognize that a single negative trial would not indicate that prazosin use in PTSD should be abandoned. If we stopped using a drug for an indication on the basis of a single negative trial, psychiatrists would not have any medications left to prescribe. Any negative trial of prazosin for PTSD would need to be interpreted within the context of existing literature, and weighed according to the relative strengths and weaknesses of all available information. Based on all currently available information, we consider prazosin to have a role in the treatment of veterans with PTSD, as currently described in the VA/DOD clinical practice guideline. That opinion may change as future information becomes available, and we certainly respect the opinion of clinicians who reach the opposite conclusion after careful review of the literature. We cannot speak to any official position the VA or DOD will ultimately have concerning the impact of Dr. Raskind’s study, and whether these new findings will ultimately impact future clinical practice guidelines.
  4. Thank you for your question and comment.

    We agree with your comment that polyprescribing should be avoided to reduce the potential for adverse drug reactions. Also, if the patient has not had a course of Evidence Based Psychotherapy this be considered as a successful outcome may obviate the need for ongoing antidepressant and adjunctive pharmacotherapy.

    Specifically to your question about adding prazosin to a trazodone and antidepressant regimen, we will assume that the patient is on a therapeutic dose of an antidepressant specifically for PTSD symptoms and a ‘sleep-inducing’ dose of trazodone. If the patient’s sleep and/or additional symptoms of PTSD improved on a bedtime target dose of prazosin, then the next step would be to taper and discontinue the trazodone.

    If after discontinuation of trazodone the patient’s symptoms remained in good control, then in consultation with the patient a gradual taper and discontinuation of the antidepressant maybe attempted. The rationale for this recommendation is that prazosin with multiple daily dosing has been reported to improve a patient’s global symptoms of PTSD.

  5. While working on an inpatient addictions unit for active duty military with a significant percentage of patients who self-medicated with alcohol and other substances for PTSD symptoms, we found Prazosin to be very beneficial for sleep and alleviation of nightmares. Generally did not combine with other sleep meds, but did not see significant side-effects when combined with SSRIs. We titrated up to 10 mg without problems and very commonly continued the same dosage after discharge. I find this dialog very useful.

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