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Nighttime-only prazosin may worsen insomnia, nightmares in PTSD

Bedtime doses of prazosin worsened nightmares and insomnia among patients with PTSD, contrary to expected findings, according to data from a pilot, randomized clinical trial.

The researchers also found that prazosin was not linked to any change in suicidal ideation or daytime-only PTSD symptoms.

“Prazosin is among the best-studied pharmacologic treatments for nightmares,” William Vaughn McCall, MD, department of psychiatry and health behavior, Medical College of Georgia, Augusta University, and colleagues wrote. “A large positive study including nonsuicidal military personnel showed an advantage of twice-daily prazosin in relieving nightmares. A larger, more recent study of military veterans was negative in the relief of sleep disturbance.”

Researchers examined whether nighttime-only prazosin would reduce suicidal ideation in 20 suicidal PTSD patients with nightmares in a randomized clinical trial. They allocated patients to receive escalating doses of prazosin or placebo at bedtime only for 8 weeks. All participants had comorbid mood disorders and continued to receive their medications. The investigators measured severity of suicidal ideation, nightmares, PTSD, insomnia and depression outcomes each week, using longitudinal mixed-effects models to evaluate change in outcomes over time.

Longitudinally, the results showed significant improvement over time across all psychometric measures among patients in both groups. However, patients who received prazosin showed less improvement in nightmare, insomnia and depression outcomes than those who received placebo as measured by the Disturbing Dreams and Nightmare Severity Index, Insomnia Severity Index, Hamilton Rating Scale for Depression and Clinical Global Impression–Severity scores.

McCall and colleagues observed no significant change in daytime measures of suicidal ideation and daytime-only PTSD symptoms in the prazosin group. In addition, the connection between final Scale for Suicide Ideation score and the final dose of prazosin approached significance.

“Overall, the research-to-date gives a confusing, mixed picture of the clinical and physiologic effects of prazosin in PTSD,” the researchers wrote.

“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 continued. “The differences between our findings and those of prior [randomized controlled trials] of prazosin might be related to the high psychiatric and medical acuity of our sample and to the complexity of the psychotropic medication regimens.” – by Savannah Demko

Disclosures: McCall reports royalties from Wolters Kluwer Health; support from MECTA and Merck; and is a scientific advisor for Sage Therapeutics. Please see the study for all other authors’ relevant financial disclosures.