EXPERT ANALYSIS FROM THE NPA PSYCHOPHARMOCOLOGY UPDATE

LAS VEGAS (FRONTLINE MEDICAL NEWS) – There is no cure for posttraumatic stress disorder, but helping its sufferers reduce symptoms, improve resistance, and achieve a better quality of life is possible.

“We have no idea what the best treatments are for PTSD,” Dr. Charles B. Nemeroff, the Leonard M. Miller Professor, and chairman of the department of psychiatry and behavioral sciences at the University of Miami, told an audience at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Whether to rely upon psychosocial or pharmacologic interventions, or a combination of the two, to help shift PTSD from a debilitating condition into a manageable, chronic one, it is important to understand PTSD as a brain disease. “To accurately treat PTSD, consider it within a neurobiological context,” Dr. Nemeroff said. “Ordinarily, the brain is evolved to deal with stress, but it can be compromised.”

In chronic PTSD, brain studies have shown a noted shrinkage in the hippocampus, contributing to memory impairment, similar to the reduced hippocampal volume in child-abuse victims. Additionally, cortical function in the brain is affected in PTSD, creating difficulty with exercising judgment and good decision making.

“One way to think about PTSD is that the cortex is unable to reign in the limbic system,” Dr. Nemeroff said. “The hippocampus is impaired, the amygdala is hyperactive, and there is a tremendous emotional drive, so the ‘thinking’ part of the brain can’t [overcome] the emotional, reptilian brain.”

The result is that a person remains stuck in a hyperaroused state. “We know that the neurobiological basis for PTSD involves a prolonged, vigilant response to stress [involving] a multitude of brain circuits … and of course the sympathetic nervous system and the pituitary and adrenal systems,” Dr. Nemeroff said.

Beyond brain changes, a genetic predisposition to PTSD accounts for a third of all cases, while an additional one-third are attributable to additional biological risk factors, according to Dr. Nemeroff ( Nature 2011;470:492-7 ).

Just as with all anxiety-related disorders, women are more PTSD susceptible than are men. One of the “few things everybody agrees on,” Dr. Nemeroff said, is that early-life trauma such as neglect or abuse is a definite risk factor for PTSD, in part because early-life stress is thought to permanently program the brain regions involved in stress- and anxiety-mediation. Add to that, any adult level trauma, and they two “synergize. The more adult trauma coupled with early childhood abuse or neglect, the higher the level of PTSD.”

Meanwhile, poor social support, especially after the occurrence of a traumatic event, is a traditional prognosticator of poor recovery from PTSD, as are a family history of mood disorders, lower I.Q. and education, and experiencing other stressors the year before or after a traumatic event.

Dr. Nemeroff said that although the goals of treatment are reduced core symptoms, improved quality of life and function, strength, and resilience against subsequent stress, “the sad fact of the matter is that we don’t have a clue what the best treatment is, because we have no predictors of treatment response for PTSD.”

The most common treatments for PTSD are selective serotonin reuptake inhibitors (SSRIs), although the best data available suggest that prolonged imaginal exposure therapy is the most effective, Dr. Nemeroff said. It can be provided either virtually or in person, and includes breathing techniques, psychoeducation, and cognitive therapy. The Institute of Medicine gives exposure therapy its highest rating for scientific evidence, said Dr. Nemeroff, who is a board member of the institute.

Pharmacologic treatments approved by the Food and Drug Administration for PTSD treatment include sertraline and paroxetine, although other antidepressants can be prescribed off-label to some effect.

With sertraline, there is a “pretty low bar” of efficacy, according to Dr. Nemeroff, since only a 30% improvement in symptoms was recorded in 60% of study participants for FDA approval. It’s important to remember the treatment-response in PTSD is much slower than in major depression, Dr. Nemeroff said. “It can take as much as 9 months, so don’t give up.”

Combining sertraline with prolonged exposure therapy is even more effective, he said ( J. Trauma Stress 2006;19:625-38 ). Meanwhile, other data show what paroxetine alone performed better than placebo, but the data are mixed for the drug in combination with prolonged exposure therapy ( Am. J. Psychiatry 2012;169:80-8 ), ( J. Clin. Psychiatry 2008;69:400-5 ), (J . Clin. Neurosci. 2008;62:646-52 ), and ( Am. J. Psychiatry 2001;158:1982-8 ).

Dr. Nemeroff said lately, he has been treating PTSD patients with venlafaxine 450 mg, which is much higher than the usual dose of about 220 mg, with “considerably good results” ( Arch. Gen. Psychiatry 2006;63:1158-65 ).

Improvements in memory and hippocampal volume generally are found with SSRI treatments, as well as reductions in symptom severity, according to Dr. Nemeroff.

For PTSD patients who are struggling with insomnia and other sleep-related problems, Dr. Nemeroff said prazosin has been “phenomenal,” especially in reducing nightmares ( Am. J. Psychiatry 2013;170:1003-10 ).

One drug class to avoid using with PTSD patients is benzodiazepines, he said. “Every study has shown that benzodiazepines in PTSD do not work, and they come with a high rate of substance abuse in this population.”

Dr. Nemeroff had no disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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