Venlafaxine Becomes First-Line PTSD Therapy in Latest VA Guidelines

Posted by: admin on: July 12, 2011

The most recent set of treatment guidelines for posttraumatic stress disorder also are the first ever to boost venlafaxine to first-line status as “strongly recommended” alongside the well-established selective serotonin reuptake inhibitors.
Another milestone in the Veterans Affairs/Department of Defense PTSD treatment guidelines released in late 2010 is that mirtazapine has risen in status to second-line therapy in response to recent mounting evidence of efficacy.

The new Veterans Affairs/Department of Defense evidence-based guidelines strongly recommend that all adults with PTSD be offered pharmacotherapy with a first-line agent. The guidelines also strongly recommend offering all patients trauma-focused psychotherapy that includes elements of exposure and/or cognitive structuring, or stress inoculation training.

Atypical antipsychotic agents are recommended as add-on therapy; the guidelines note that the strongest evidence is for risperidone. Dr. Villarreal said his personal practice is to reserve the second-generation antipsychotic agents for the most severe cases, including those involving psychosis or severe dissociation, because of the significant metabolic and other side effects accompanying use of these drugs.

The VA/DoD guidelines specifically do not recommend benzodiazepines, tiagabine, guanfacine, valproate, or topiramate. None of these drugs has demonstrated evidence of benefit.
The VA/DoD list of “insufficient evidence” medications is seen as a nod toward the Institute of Medicine (IOM), which in October 2007 released an influential review of the research evidence on PTSD treatments. The report concluded that the strongest evidence of efficacy is for exposure-based therapies, and that there is also some evidence for cognitive restructuring, teaching of coping skills, and eye movement desensitization and reprocessing. But as for pharmacotherapy, the quality of the studies up to that point was so flawed that the IOM panel concluded that no evidence-based medication exists for the treatment of PTSD.

He noted that most of the numerous PTSD treatment guidelines recommend SSRIs as first-line therapy. Indeed, the only two Food and Drug Administration–approved treatments for the disorder are the SSRIs sertraline and paroxetine, although in Dr. Villarreal’s experience the efficacy of SSRIs is probably a class effect.
“I would say the SSRIs are helpful, but it’s really a modest response, not a dramatic response,” he said. “You rarely see remission of symptoms.”

Although the VA/DoD guidelines recommend venlafaxine as the best-supported option among the SNRIs, which together with the SSRIs are considered first-line agents, Dr. Villarreal noted that last year saw publication of two highly promising albeit open-label studies of duloxetine in PTSD.

The antiadrenergic agent prazosin is gaining increasing use in PTSD on the strength of several positive studies, including one that showed efficacy comparable to that of quetiapine but with far fewer side effects. Dr. Villarreal is an investigator in an ongoing clinical trial in which male veterans are titrated fairly quickly to 20 mg/day of prazosin with regular blood pressure monitoring for possible hypotension.

Yet Dr. Villarreal was a co investigator in an as-yet unpublished multicenter, randomized, placebo-controlled trial of quetiapine monotherapy for PTSD that he said yielded “very impressive findings.”


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