Is prazosin effective for trauma related nightmares? Am Jl Psych. Sept.2013

13.12.2013

Nightmares in PTSD can be extremely distressing for patients . Usual treatments for PTSD ( SSRIs )  often fail to stop these symptoms. Medications like risperidone and trazadone are tried to reduce nightmares with varying benefits. Side effects of these medications like sedation, weight gain and sexual dysfunction can be problematic, especially in active duty soldiers.

Excessive adrenergic activity in brain  explains some of the PTSD symptoms. Could medications that reduce the  norepinephrine effects at CNS alpha-1 adrenoreceptors  be effective in reducing some of the difficult symptoms of PTSD?

Murray A. Raskind  and team of researchers from Seattle studied the effectiveness of Prazosin for nightmares in PTSD in this RCT. Prazosin is an alpha-1 adrenoreceptor antagonist  with a short half-life (3-4 hrs). It does not cause  sedation, sexual dysfunction, dyslipidemia, hyperglycemia, or weight gain. Previous research has shown benefits with this medication in PTSD (Raskind   et al, 2003,2007, Calohan 2010, Germain et al 2012).

Study was performed at a Washington army facility. 65 active duty soldiers were recruited (2009-2011). Individuals with DSM 4 diagnosis of PTSD  following combat trauma( with severity score above 50 on CAPS) with distressing combat-related nightmares  for at least 2 nights per week ( night mare item on CAPS to score at least 5 out of 8) were only eligible for participation.Those with  current substance use disorders, depression requiring hospitalisation and active suicidal ideas were excluded.

Participants received  either prazosin capsules (1 mg, 2 mg, and 5 mg) or  placebo capsules for 15 weeks.Medication was initiated at 1 mg at bedtime for 2 days and increased to 2 mg at bedtime for the next 5 days. Morning dose was started on week 2. The dosage was further increased at weekly intervals  ( for max 6 weeks) unless trauma nightmares disappeared for one week / adverse effects were rated greater than mild, or the maximum allowed dosage had been reached. (Max dose was set as 5 mg mid morning, 20 mg bed time for men,  2 mg and 10 mg in women, as women are thought to be more sensitive to benefits & side effects). Dose titration  and rating was done by blind clinicians. CAPS nightmare item, the Pittsburgh Sleep Quality Index , and the Clinical Global Impressions Scale (CGI) were the primary outcome measures. 

Mean  dose of prazosin was 4 mg (mid morning)  and 15 mg (night) among men,  1.7 mg  (midmorning) and 7 mg (night) among women.

Results:

Prazosin was significantly superior to placebo for all three primary outcome measures .The mean change in total CAPS score from baseline to endpoint was 25.1 for the prazosin group, compared with 13.8  for the placebo group. ( mean baseline score was 84).The decrease in CAPS nightmare item score from baseline to endpoint was 3.1  in the prazosin group and 1.2  in the placebo group. Decrease in score on the Pittsburgh Sleep Quality Index from baseline to endpoint was 5.6  in the prazosin group and 2.8.Those not on SSRI improved better, though numbers were small to conclude this with any certainty . Hyperarousal cluster improved significantly.

Two serious  adverse events occurred were both in placebo group.Blood pressure did not significantly differ over time or between treatment groups. 

The difference of 11.3 points in improvement in CAPS score between the prazosin and placebo groups exceeds the 9-point difference in CAPS score proposed as a threshold for clinical importance. This difference is comparable to approved treatments for PTSD. Mid morning dose also might have helped in reducing overall symptoms ( as opposed to benefit on nightmares alone in previous studies).

 Though found safe, sample size  is not sufficient  enough to conclude this. An earlier study have used (Calohan et al)  prazosin in soldiers deployed in Iraq and found it safe. Maintaining hydration is important while on Prazosin. 

Conclusion:

Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers . It appears to be well tolerated.

Summary of the article: 

trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan.

Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, Homas D, Hill J, Daniels C, Calohan J, Millard SP, Rohde K, O’Connell J, Pritzl D, Feiszli K, Petrie EC, Gross C, Mayer CL, Freed MC, Engel C, Peskind ER. Am J Psychiatry. 2013 Sep 1;170(9):1003-10

 

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