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New Research on the Prevention of PTSD

February 19, 2010

Post-Traumatic Stress Disorder (PTSD) has been widely known for decades, mostly in the context of troubled military veterans returning from combat zones. But, as the National Institute of Mental Health (NIMH) points out, PTSD is an anxiety disorder that can develop after any number of traumatic or life-threatening experiences, including military combat, natural or man-made disasters, violent personal attacks, even car accidents.

Much has been done to recognize and treat PTSD as a biologically based disorder in the last 20 years, including the formation of the National Center for PTSD through the US Department of Veterans Affairs and inclusion in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). But the exact cause(s) and best treatment(s) are still under investigation. The crew over at the Discover magazine blog 80beats discussed two recently published studies on the diagnosis and prevention of post-traumatic stress disorder (PTSD). Here I link to and discuss the study on a possible way to prevent PTSD.

Study – Could morphine given during early trauma care decrease the likelihood that a wounded soldier will develop PTSD?

A new study published in the January 14, 2010 issue of the New England Journal of Medicine by Holbrook et. al shows an interesting correlation between treatment with morphine and the incidence of PTSD in soldiers wounded in combat.

This study examined the military medical records of 696 military personnel injured in combat during Operation Iraqi Freedom (Jan. 2004 – Dec. 2006). Of these 696, 243 developed signs of PTSD within 2 years of their injury. PTSD was defined by the criteria in the DSM-IV and diagnosed by either military or civilian medical personnel. Of the soldiers later diagnosed with PTSD, only 61% received morphine during their early trauma care. Of those without PTSD, 76% received morphine. This is a statistically significant difference, meaning the likelihood that this difference is due to chance is very low.

Could this association mean that morphine is protective against PTSD?

It’s possible. Soldiers who got morphine were less likely to later get PTSD, but all the researchers know is that these two factors change together, not that one leads to the other (correlation, not causation). With a retrospective, observational study like this one, correlation is the best anyone can expect. The researchers are looking back in time (retrospective), so they can’t go back and see if the servicemen were showing signs of PTSD before their injury, or choose soldiers to follow over time regardless of whether or not they were injured. They also have to go with the data that they have, even if it is messy and uncontrolled (observational evidence) rather than directly manipulating the situation (experimental evidence) because it would be sick and wrong to deny pain relief to wounded soldiers for the sake of controlling who got morphine, how much, when, etc.

What are the limitations of this study?  How strong is the conclusion?

There are some ways to test the correlation and firm up the conclusion that morphine really is the reason the soldiers were less likely to develop PTSD. The researchers tried to determine if there were other factors that could be helping to prevent PTSD by comparing those who developed PTSD and those who did not. The median age of the two groups was identical, and 99% of all the people in the study were male, so age and sex could not have been factors in the prevention of PTSD. Both groups had similar mechanisms of injury (improvised explosive devices or IEDs, gunshots, grenades, etc) and when the severity of injury was compared using the Injury Severity Scale (0-75 with >16 being considered severe) the soldiers that did not develop PTSD were actually more likely to have a serious injury. This goes along with the morphine correlation, the more severe the injury the more likely the soldier would be to receive morphine during early trauma treatment.

The researchers tried to look for a time or dosage affect with the morphine. If larger or faster doses of morphine lead to better outcomes with respect to PTSD, this could strengthen correlative evidence. Fortunately for the soldiers (but not for the researchers) 71% of all soldiers were treated with morphine within an hour of their injury, and no difference was found when time to treatment was factored in. The amount of morphine given was highly standardized, ranging narrowly from 0-20 mg and averaging 5 mg by IV injection for both the group that developed PTSD and those that did not. Protective and non-protective effects were seen for all amounts, so they cannot say if more morphine is better for preventing PTSD. The researchers did note that morphine was the main psychoactive medication (medication that can affect mental state) given to the soldiers, and that use of other medications like benzodiazephines or other opiates was rare. This means that morphine, and not another medication, is the best candidate for PTSD prevention.

What is the future of this research?

More work will have to be done to determine for certain that morphine is the reason for the decrease in PTSD, but right now the link is promising. How is the morphine working? That is currently unknown. One hypothesis is that the morphine is acting on the brain to either block the formation of traumatic memories and/or prevent the link between memory and the fear response that characterizes PTSD. Another hypothesis comes from studies that show that patients who report feeling low levels of pain are less likely to develop PTSD after their injury than patients who report high levels of pain. This suggests that effective pain management (through morphine or other methods) could be the key to preventing PTSD.

The study was done by researchers at the Naval Health Research Center in San Diego, CA, USA with consent from the Naval Health Research Center review board. The lead author on the study also lists an affiliation with EPI-SOAR (Epidemiology & Surgical Outcomes Assessment Research) Consulting, Inc. a consulting firm that helps the Department of Defense with epidemiological research.

The Discover magazine blog post for this story is here.

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