Monday, September 13, 2010

New Treatments for Post-traumatic Stress

A new therapeutic approach is in sight for treatment of traumatic memories, including memories that cause PTSD. Two lines of memory research have converged to produce a treatment, and sometimes even a cure, for the most serious need to forget, PTSD. This may not be generally known or accepted, but at least two research groups have shown there is a blood pressure drug, propranolol, that helps us to forget overwhelmingly stressful memories and thus reduces the stress that goes with those memories. The latest treatment being investigated by some researchers is based on using a common blood pressure drug, propranolol, which has a side effect of blocking the re-consolidation of emotions associated with old memories when those memories are recalled.

One reason it is possible to forget or at least edit memories is that when even well-formed memories are recalled, they are put back on the scratch pad of working memory where they are accessible to “editing” and re-consolidation. As I explained in a  previous blog column, each time a memory is retrieved, it can get changed and re-stored in a different way.

While memories reside on the scratch pad of working memory, either for the first time or during any recall episode, they can be changed by drugs. Also relevant here is that memory consolidation is greatly influenced by the impact of the experience, which is magnified by strong emotion and the hormones such emotions release. During re-consolidation, under conditions of proper talk therapy, the emotional impact need not duplicate the original and a more benign version will be stored in memory.

The rationale for testing propranolol was developed in the seminal work by Roger Pitman and colleagues. They noted earlier studies showing that adrenalin (epinephrine), either injected or released naturally under stressful conditions, strengthens memory formation and fear conditioning. Adrenalin helps you to remember the bad event and hopefully you can avoid facing that threat again by being alert and prudent. Adrenaline acts on a class of molecular receptors called beta-adrenergic receptors. Certain drugs, among them propranolol, block beta receptors and thus might theoretically disrupt fear-induced memories. Several groups have confirmed that propranolol does impair fear-conditioned memory in both animals and humans.

Pitman’s group sought to extend this notion to PTSD in a pilot study of 41 patients. They conducted a double-blind, placebo-controlled study in which a single 40 mg oral dose of propranolol was given as soon as possible (within 6 hours) after a traumatic event experienced by patients who had been rushed to a hospital emergency room. Patients then continued the medication four times a day for 10 days followed by a 9 days when the dose was progressively reduced to zero.

One and three months later, patients returned for psychological testing aimed at measuring PTSD. At one month post trauma, the number of patients with PTSD in the propranolol group was almost half that of placebo controls. Not tested was the possibility that a larger dose, especially if given early or prior to the unpleasant experience, might be even more effective, since there probably is a narrow window of opportunity for the drug to be beneficial in impairing the consolidation of bad memories.

A similar result was obtained in a later study by Guillaume Vaiva and colleagues. Their hospital emergency room patients were given propranolol or a placebo 2-20 hours after experiencing an auto accident or physical assault. The patients tested were also selected for having abnormally fast heart rates, because propranolol is a common therapeutic for that condition. Propranolol was given in a dose of 40 mg three times daily for seven days, followed by gradual reduction to zero over 8-12 days.

Under the common situation where emotional trauma has already been consolidated, the obvious treatment approach for PTSD might be to have patients recall the traumatic event later while under the influence of propranolol. The idea is that during recall, the memory and its associated emotion have to be reconsolidated, and this is disrupted by the drug. Indeed, this idea is being hailed in some quarters as a possible major breakthrough in treatment of PTSD. Many positive results are being reported by physicians, and the Army is considering using this approach for combat-related PTSD. The National Institute of Mental Health is now recruiting patients for a Phase IV Clinical trial.

One obvious conclusion is that propranol might be a good PTSD preventive drug if given before an anticipated traumatic event. For example, I wonder if D.O.D. psychiatrists have thought about giving propranolol to combat troops just before they engage in battle.

Another issue that nobody seems to consider is the possibility that people on this kind of blood pressure medication might be suffering impairments of emotional memories that they don't want to lose. Does this drug cause a general dulling of emotions? Could it magnify the failing memories of the elderly?


Copyright 2010, W. R. Klemm. Dr. Bill Klemm is a Professor of Neuroscience at Texas A&M University. Visit his book site and blog at ThankYouBrain.com for more help on improving memory.

No comments:

Post a Comment