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. 

Conflicting Data

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.