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David Baxter PhD

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Try Psychosocial Therapies, Prazosin for PTSD
By NEIL OSTERWEIL, Clinical Psychiatry News
July 21, 2011

BOSTON ? Exposure to trauma is ephemeral, but its effects in the form of posttraumatic stress disorder can linger for decades. However, a handful of psychosocial therapies and at least one class of drugs can be effective at reducing the invisible scars of PTSD, investigators reported at a conference on the complexities and challenges of PTSD and traumatic brain injury.

Interventions such as exposure therapy, cognitive processing therapy, and eye movement desensitization and reprocessing can help PTSD sufferers direct their thoughts away from traumatic events, often with durable results, said Terence M. Keane, Ph.D., director of the behavioral science division of the National Center for Posttraumatic Stress Disorder, Boston.

In addition, "emerging, exciting evidence" supports the use of the alpha-adrenergic antagonist prazosin for alleviating nightmares and sleep disruptions associated with the disorder, said Dr. Thomas A. Mellman, research associate dean and professor of psychiatry at Howard University, Washington.

Impact of Trauma Exposure
In an era of multiple military deployments and widespread regional conflicts, levels of PTSD and comorbid conditions are increasingly common, noted Dr. Keane, who also is with the department of psychiatry at Boston University.

"If there is one powerful determinant of who develops PTSD, it is exposure to trauma experiences," he said. "It overrides all of the other risk factors. It outranks everything else, including childhood upbringing."

Many of the scales that are used to assess PTSD and combat exposure were developed after the Vietnam War. The Combat Exposure Scale, published by Dr. Keane and his colleagues in 1989, is a 7-item questionnaire gauging PTSD risk by factors such as the degree of exposure to firefights, the number of casualties in the soldier?s unit, and frequency of exposure to life-threatening situations (Psychol. Assess. 1989;1:53-5).

The scale?s upper limit of the numbers of exposures to firefights is "51 or more." In contrast, U.S. soldiers were exposed to about 400 firefights during a 15-month deployment in the Korengal Valley in Afghanistan, said Dr. Keane, citing Sebastian Junger, an American journalist who was intermittently embedded with a platoon of the 173rd Airborne Brigade in 2007-2008.

"The most upsetting thing ... was the loss of their friends," Mr. Junger wrote. "They felt responsible for their deaths, convinced there was something they could have done to prevent them and a sense of guilt that they should have been killed instead."

Psychosocial Interventions
There are five evidence-based psychosocial interventions for PTSD: exposure therapy, cognitive therapy, anxiety management, cognitive reprocessing therapy, and eye movement desensitization and reprocessing (EMDR).

"It?s very clear that participating in these treatments if you have a diagnosis of PTSD actually leads to remarkable improvement not only in symptoms, but also in life functioning," Dr. Keane said.

Cognitive-behavioral treatments for chronic PTSD approach the problem from two different angles. One approach allows patients to safely confront their traumatic experience through exposure discussions that recall trauma reminders; the other is aimed at modifying the dysfunctional thought processes that underlie PTSD.

One example of the former approach is exposure therapy, in which patients confront the objects, situations, memories, and images they fear in a systematic and repetitive fashion. After an initial relaxation training session, patients relive their experiences through imagined exposures to the traumatic memory, and, when possible, with real-life exposure to the traumatic event (for example, a visit to a car accident site).

"This is a very powerful treatment that effectively reduces symptoms of PTSD and improves psychosocial functioning in virtually every domain that we have tested," Dr. Keane said.

An alternative approach is cognitive therapy, in which patients are helped to change their negative, unrealistic thinking by identifying their dysfunctional, unrealistic thoughts and beliefs ("I?m responsible for it," "It was what I was wearing," "I should never have been there"), and challenge those distortions, helping the patient to replace them with functional, realistic alternatives.

Cognitive processing therapy (CPT) combines elements of the exposure and cognitive therapy approaches. It involves cognitive restructuring focusing on safety, trust, power, esteem, and intimacy. The patient repeatedly writes out the traumatic experience and reads it in 12 weekly sessions.

EMDR has been shown in controlled studies to help patients with PTSD, with an effect comparable to that of exposure therapy in many instances, Dr. Keane said. As in the latter treatment, EMDR accesses trauma images and memories, and helps patients to evaluate the aversive qualities of those images and memories, and to generate alternative cognitive appraisals. The recall is accompanied by sets of lateral eye movements that the patient makes while focusing on her/his response.

"There has been a lot of discussions on the eye movements ? are they necessary, are they not necessary ? [and] it looks like the best data suggest that they?re not necessary," Dr. Keane said.

Pharmacologic Interventions
When it comes to drug therapies for PTSD, many have been tried and most have been found wanting, Dr. Mellman said.
Pharmacotherapy for PTSD is based on neurobiological models of PTSD involving memory and neural structure. These models link PTSD to reactivity or selective attention to trauma stimuli, fragmentary trauma narratives, verbal memory deficits, reduced hippocampal volume, and increased amgydala activation with reduced anterior cingulate activation, he said.

Proposed hormonal and neurotransmitter-related mechanisms include reduced cortisol secretion and increased sensitivity to feedback inhibition, an effect of noradrenergic activity on fear-enhanced learning, and the role of the excitatory amino acid glutamate in neuroexcitation, learning and neurotoxicity, and GABA (gamma-aminobutyric acid) in inhibition.

Some evidence supports the use of selective serotonin reuptake inhibitors (SSRIs), which have been shown in nine randomized controlled trials in primarily female civilian populations to have positive effects on the three PTSD symptom clusters (reexperiencing, avoidance, and hyperarousal). Response rates in these studies have ranged from 53% to 64% (compared with 32% to 38% for placebo), with the effects occurring both with and without comorbid depression. In one study, maintenance efficacy of up to 1 year was seen with patients on sertraline.

However, six other published randomized controlled trials failed to find a benefit for SSRIs for PTSD symptoms, compared with placebo. These studies primarily involved men, many of whom were veterans, Dr. Mellman noted.

Other agents with mixed or limited evidence to support their use in PTSD include atypical antipsychotics, benzodiazepines, MAO inhibitors, tricyclics, and anticonvulsant mood stabilizers, Dr. Mellman said.

Seven small randomized controlled trials have looked at atypicals, primarily risperidone and olanzapine, and primarily in treatment-refractory patients.

"Overall, the evidence does support adjunctive risperidone for refractory cases, and there does seem to be a benefit to sleep for the atypical class," he said.

Regarding benzodiazepines, there appears to be a lack of evidence to support either their efficacy or inefficacy, he added. "We don?t recommend benzodiazepines as treatment for people with PTSD, but does that mean people with PTSD shouldn?t be exposed to them? I?m not sure. They do calm a person down temporarily, but [we should be] wary of continuous, chronic application," he said.

Prazosin Proves Powerful
Prazosin, originally developed as an antihypertensive agent, has been shown to have efficacy at reducing insomnia and nightmare in veterans with PTSD.

A study of 34 veterans with chronic PTSD and trauma nightmares showed that prazosin "shifted dream characteristics from those typical of trauma-related nightmares to those typical of normal dreams" (Biol. Psychiatry 2007;61:928-34).

"Prazosin also appeals to me from a theoretical standpoint because it preserves REM sleep, in contrast to many pharmacological agents that have the effect of reducing REM sleep, and there?s a particularly interesting animal model that shows that [prazosin] preserves REM sleep against the disruption of an adrenergic agonist, and this may be a model that?s relevant to PTSD," Dr. Mellman said.

Dr. Keane and Dr. Mellman presented their findings at a symposium supported by the Home Base Program, a joint project of the Red Sox Foundation and Massachusetts General Hospital, both in Boston. Neither Dr. Keane nor Dr. Mellman had relevant financial disclosures.
 
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