Posttraumatic Stress Disorder in Veterans

The treatment of PTSD is, at first blush, fairly straightforward. The Cochrane Collaboration, a leading source in evidence-based medicine, has published 3 systematic reviews related to PTSD treatment. The 2006 pharmacotherapy review of randomized controlled trials found that medications, primarily SSRIs, are effective in reducing core PTSD symptoms and associated depression and disability.⁸ The overall response rate was 59.1% compared with a 38.5% placebo response, leading to an overall number needed to treat of approximately 5. Not surprisingly, medications were found to be less well tolerated than placebo. These results concur with the common clinical practice of using SSRIs to treat PTSD; indeed, sertraline and paroxetine are the only FDA-approved treatments for PTSD.

The recently published psycho-therapy review reported that CBT or, more specifically, trauma-focused CBT with exposure therapy and eye-movement desensitization and reprocessing, was effective and should be considered for persons with PTSD.⁹ Non-trauma-focused therapies were found to be ineffective. The authors noted that there was some evidence of a greater dropout rate in the active treatment groups; this does not seem surprising given that avoidance is a hallmark of PTSD, and these treatments share exposure to trau-matic memories as the basis of their effectiveness.

The recent Institute of Medicine report evaluated the effectiveness of psychotherapy and pharmacotherapy and found that only exposure-based therapies had sufficient evidence of efficacy. The report, however, pointed out that this should not be misconstrued to imply that only exposure-based therapies should be used. The authors noted it was mostly indicative of a lack of appropriately designed studies for other treatments.

The third Cochrane review pertinent to PTSD treatment evaluated the effectiveness of psychological debriefing, including the often-used Critical Incident Stress Debriefing.¹⁰ To be blunt, single-session psychological debriefing does not work and actually may be harmful. Despite its wide intuitive appeal, there is no evidence from any of the studies that such treatments, although still frequently used, have any significant benefits. More alarming, the studies with the longest follow-up indicate that debriefing may actually increase the risk for PTSD or at least impair the natural healing process. This seems somewhat obvious in retrospect, because a single-session exposure seems more likely to cause sensitization than desensitization.

Treatment of PTSD in veterans is more complicated than such reviews would suggest. First, there is some evidence that medications are not as effective for combat veterans as they are for civilians, and there is very little research on antidepressants in combat veterans. An early, small study using fluoxetine to treat PTSD in veterans and nonveterans reported that veterans showed much less improvement than nonveterans.¹¹ Another study, which was conducted more than a decade ago but published this year, evaluated the benefits of sertraline in Vietnam veterans with combat-related PTSD.¹² This VA-funded, 12-week, multicenter study treated 169 veterans with chronic PTSD with sertraline (mean dose, 135 mg) or placebo. Most of the patients were Vietnam veterans who had experienced symptoms for more than 20 years.

The authors found that there were no differences between sertraline and placebo on any symptom outcome measure. This is a disappointing finding, although it is not entirely surprising given the chronic nature of these veterans' symptoms. Clearly, there is a difference between recently traumatized female rape victims and male Vietnam veterans whose trauma may have occurred decades before treatment; SSRI treatment may be useful for some forms of PTSD and not others. In addition, other issues, such as VA compensation for disability, may affect both the presentation of PTSD in VA settings and response to treatment. It also remains uncertain whether SSRI treatment is beneficial when used more acutely following combat exposure.

One medication, prazosin, has predominantly been studied in veteran populations with chronic PTSD and appears to show particular promise for treatment of disabling nightmares and sleep disturbances. Prazosin is a centrally acting α₁-blocker; it is believed that prazosin attenuates physiological responses to elevated norepinephrine levels that are frequently found in chronic PTSD. Several small studies have shown benefits of prazosin for combat and non-combat-related PTSD using both daytime and evening doses.

The largest and most recent study involved 40 combat veterans with PTSD.¹³ In this 8-week, placebo-controlled study, prazosin was titrated to a mean dose of 13.3 mg, given at bedtime. The investigators found large differences in the effects of prazosin compared with placebo on measures of sleep quality and traumatic nightmares. Interestingly, patients also reported a normalizing of their dreams—moving from experiences of traumatic nightmares to less troubling dreams.

Unfortunately, other PTSD symptoms were not improved, although 71% of patients treated with prazosin were regarded as "moderately or markedly improved" on a global measure compared with only 12% in the placebo group. This global benefit seemingly relates to the profound effect that nightmares and sleep disturbance have on the general well-being of patients with PTSD. Larger studies are currently evaluating whether additional daytime dosing with prazosin could improve overall PTSD symptoms. Curiously, the authors found no effect on blood pressure from the antihypertensive agent, although our clinical experience is that some patients do not tolerate the high doses usually associated with hypertension.

Prazosin is not FDA-approved and studies to date have been limited. Thus, future research is needed before prazosin is accepted as an evidence-based treatment for PTSD.

The war in Iraq and the Afghanistan operation have had, and will continue to have, profound effects on military service members returning from combat. Psychiatrists will be faced with treating psychological conditions that historically have not responded well to treatment. The patients have complex social, psychological, and medical needs, and a range of biopsychosocial treatments may be necessary to help them.

Novel treatments, such as virtual reality exposure therapy, have yet to be proved effective. Standard treatments, such as vocational rehabilitation and substance abuse treatment, may help with the difficulties often associated with combat experience. The pharmacotherapy of PTSD should begin with SSRIs, and practitioners should remember that only sertraline and paroxetine have been FDA-approved. Preliminary research has shown that prazosin may be helpful for sleep disturbances associated with PTSD. However, more research is clearly needed in the treatment of combat- related PTSD, a vexing mental illness that haunts many veterans.