September 2007

Prazosin for PTSD Nightmares
Adjunctive treatment with the α1-blocker prazosin (Minipress and others) reduces trauma nightmares and sleep disturbance in patients with posttraumatic stress disorder.

Treating Bipolar Depression
Antidepressants add little benefit in treating bipolar depression, but the risk of inducing mania appears small.

Are SSRIs Teratogens?
There is a small risk of congenital malformations with fetal exposure to selective serotonin reuptake inhibitors, particularly paroxetine (Paxil and others), during the first trimester.

In Brief
Benefits of Antidepressants versus Suicide Risk; Rivastigmine Does Not Slow Progression to Alzheimer's Disease

Antidepressants Can Help Prevent Depression after Stroke
Antidepressant drugs may provide relief for many patients suffering from depression following stroke.

Prazosin for PTSD Nightmares

September 2007

Symptoms of posttraumatic stress disorder (PTSD) typically last for decades. Modern antidepressants, most commonly selective serotonin reuptake inhibitors (SSRIs), produce remission in roughly one-quarter to one-half of civilians with PTSD. Response rates in combat veterans tend to be much lower. Among symptoms most resistant to antidepressant monotherapy are nightmares and sleep disturbances. These contribute to suffering and probably account for substantial comorbid alcohol and drug abuse, as well as suicidal thoughts and acts.

Raskind and coworkers have hypothesized that PTSD nightmares differ from usual dreams in that they occur during light sleep.1 To reverse α1-adrenergic stimulation that might underlie these nocturnal events, they proposed adding the α1-blocker prazosin (Minipress and others) to a PTSD treatment regimen to decrease light sleep and normalize rapid eye movement (REM) sleep. In a 10-subject, placebo-controlled, crossover study in Vietnam combat veterans, these investigators found that prazosin substantially reduced PTSD trauma nightmares and sleep disturbance and improved global clinical symptoms and depression.2 Subjects reported that when trauma nightmares were reduced, normal dreaming returned.

Studying another group of combat veterans with chronic PTSD, intractable nightmares, and sleep disturbance, Raskind and colleagues added either prazosin or placebo to patients' medication regimens, which consisted mostly of antidepressants.3 In this 8-week trial, 17 patients received prazosin, while another 17 took placebo.

Once again, adjunctive prazosin was significantly superior to placebo in reducing trauma nightmares and improving both sleep quality and global clinical status. Trauma-related nightmares yielded to more normal dreams. There were no blood pressure differences between patients in the prazosin group and those taking placebo, nor were there episodes of falls or syncope. Prazosin seemed to cause nasal congestion and headache.

Prazosin is an inexpensive, generically available medication labeled for the treatment of hypertension. It is also used off-label to improve urination in patients with benign prostatic hypertrophy and to treat symptoms of Raynaud's syndrome. Prazosin is the α1-adrenergic antagonist that most easily enters the brain, which is why Dr Raskind's group chose it for their experimental work.

PTSD is a common psychiatric syndrome. With ongoing wars, terrorism, and natural disasters, many new cases occur each year. Antidepressant medications and specific forms of psychotherapy can help many patients, but when sleep disturbances and, in particular, trauma-related nightmares are a problem, prazosin might be a useful adjunctive intervention. At this stage, research remains preliminary, but many psychiatrists who treat these patients are using it off-label and informally reporting positive outcomes.

1Krystal AD, Davidson JRT: The use of prazosin for the treatment of trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry 2007;61:925-927.

2Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Tröster K, Thomas RG, McFall MM: Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: A placebo-controlled study. Am J Psychiatry 2003;160:371-373.

3Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, Shofer J, O'Connell J, Taylor F, Gross C, Rohde K, McFall ME: A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry 2007;61:928-934.