Contrary to expectations, the alpha-adrenergic blocker prazosin (Minipress, Pfizer), which is used to treat high blood pressure as well as posttraumatic stress disorder (PTSD), may worsen nightmares and insomnia and does not appear to reduce suicidal thoughts, new research suggests.
"I was unpleasantly surprised at the result. Prazosin had been gaining substantial traction as a treatment of choice for nightmares and other PTSD-related symptoms," principal investigator William Vaughn McCall, MD, chair of the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University, told Medscape Medical News.
This is the first study of prazosin in which all participants were experiencing suicidal ideation in addition to PTSD and nightmares.
"To state the obvious, the present literature shows that prazosin is clearly 'not for everyone,' and discretion is advised when prescribing," said McCall.
The study was published online November 19 in the Journal of Clinical Psychopharmacology.
Two earlier studies of prazosin for PTSD-related sleep problems yielded mixed results.
A study of nonsuicidal military personnel with PTSD that was published in 2013 showed that twice-daily prazosin was beneficial in relieving nightmares.
A study published in February of this year failed to show a benefit of twice-daily prazosin over placebo in reducing PTSD-related nightmares. In this study, however, new or worsening suicidal ideation occurred as an adverse event in fewer patients taking prazosin than placebo (8% vs 15%).
McCall and colleagues conducted a pilot, randomized clinical trial to test whether treatment with prazosin would reduce suicidal ideation in 20 suicidal patients with PTSD and nightmares.
Patients were randomly assigned to receive escalating doses of prazosin or placebo at bedtime for 8 weeks. The final highest dose for men and women combined was 5.5 ± 3.5 mg for prazosin and 7.6 ± 5.3 mg for placebo.
All participants had comorbid mood disorders and were receiving stable doses of mood disorder medication. Outcomes of interest, measured weekly, included severity of suicidal ideation, nightmares, PTSD, insomnia, and depression.
Patients in both groups demonstrated improvement over time in all psychometric measures. However, compared with patients taking placebo, those taking prazosin had significantly less improvement in nightmares, as measured by the Disturbing Dreams and Nightmare Severity Index; insomnia, as measured by the Insomnia Severity Index; and depression, as demonstrated by Hamilton Rating Scale for Depression and Clinical Global Impression–Severity scores.
There was no significant change in suicidal ideation with prazosin.
The results failed to support the study's main hypothesis that bedtime doses of prazosin would have a favorable effect on suicidal ideation, the researchers say. "Bedtime-only doses of prazosin had a significant effect on nighttime variables such as nightmares, insomnia, and depression scores (which include sleep items), albeit that the effects were in the direction opposite of expected," they write.
One patient each in the prazosin and placebo groups required emergency psychiatric hospitalization for worsening suicidal ideation or worsening clinical condition. There were no suicide attempts or deaths.
McCall and colleagues say the differences between their findings and those of prior randomized controlled trials of prazosin in PTSD could be related to the high psychiatric and medical acuity of the sample and to the complexity of the psychotropic medication regimens.
Overall, studies to date provide a "confusing, mixed picture of the clinical and physiologic effects of prazosin in PTSD," they conclude.
McCall told Medscape Medical News that, in his opinion,"the entire approach to prazosin in PTSD needs to be rethought out.
"We need to reconcile how is it that we had 10 years of data saying prazosin is good for nightmares in PTSD, a big study this February indicating it has essentially no effect, and now a smaller study showing it can worsen some aspects. We need to know what it all means," he added in a news release.
McCall said he would advise against giving prazosin to suicidal PTSD patients taking complicated psychopharmacology regimens "and that consideration be given to discontinuing it if the patient shows equivocal response after a month or two."
Reached for comment, Matthew Johnson, PhD, of the Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, said the results are "noteworthy" and "concerning for the use of the drug in PTSD patients.
"However, it should be noted that this is a relatively small sample of 10 vs 10 patients in the drug and placebo groups & — very few for a between-subjects randomized design. In order to be more confident that the worse insomnia and nightmares really are an effect of prazosin, a larger study would be needed," said Johnson.
The study was supported by a grant from the American Foundation for Suicide Prevention. Dr McCall receives royalties from Wolters Kluwer Health and research support from MECTA and Merck and is a scientific advisor for Sage Therapeutics. Dr Johnson has disclosed no relevant financial relationships.
J Clin Psychopharmacol. Published online November 19, 2018. Abstract
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