"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.