Morphine shows promise against post-traumatic stress disorder

Early administration of morphine to military personnel wounded on the front lines during Operation Iraqi Freedom appears to have done more than relieve excruciating pain. Scientists believe it also prevented hundreds of cases of post-traumatic stress disorder, the debilitating condition that plagues 15% of those who have served in Iraq and Afghanistan.

That conclusion is based on findings published today in the New England Journal of Medicine. They suggest that a simple treatment can stop a single horrifying event from escalating into a chronic, incapacitating illness.

Small clinical trials and observational studies have hinted that opiates and other medications could disrupt the way the brain encodes traumatic memories, thus preventing the incidents from being recorded with too much intensity. The new findings -- troops who received morphine within a few hours of their injuries were about 50% less likely to develop PTSD than those who didn’t get the powerful painkiller -- are a strong endorsement of that theory.

The results underscore the potential for preemptive treatment not just for soldiers, but for victims of war, natural disasters, physical abuse, violent crimes such as rape, and traumatic accidents.


PTSD is a relatively common disorder in which stress seems to cause normal memory systems to go into overdrive. It can cause vivid flashbacks, sleep difficulties and problems with relationships. Symptoms can begin soon after a traumatic event or years later.

“We’re all worried about the mounting incidence of PTSD among our troops, as well as the incidence in the civilian sector,” said Dr. Matthew J. Friedman, executive director of the Department of Veteran Affairs’ National Center for Posttraumatic Stress Disorder in White River Junction, Vt., who wasn’t involved in the study. “If there were something we could do to prevent that, why wouldn’t we do it?”

More than 40,000 military personnel have been diagnosed with PTSD since the 2003 invasion of Iraq, and Defense Department officials say many more surely have the disorder but have not sought treatment.

Overall, experts estimate that about 20% of troops and veterans suffer from PTSD, along with 8% of civilians.

Treatment usually involves talk therapy to help patients change how they react to painful memories, and antidepressants and other medications can sometimes ease symptoms. But these approaches leave much to be desired.

“PTSD right now is really difficult to treat, so if we had a prevention, we’d want to use it,” said Dr. Murray Stein, a UC San Diego psychiatrist and director of the Injury and Traumatic Stress Clinical Consortium, which is funded by the Defense Department.

Psychiatrists and neuroscientists aren’t sure why some people develop PTSD while others don’t, but the leading theory is that too much of the stress hormone norepinephrine at the time of a traumatic event causes the brain to malfunction when it records the memory.

The idea behind the preventive treatment approach is to disrupt the transmission of norepinephrine in the brain, either by blocking its release or by preventing it from binding to a receptor. In either case, a drug would have to be administered very early, while the memory was still being encoded.

The first hint that morphine could serve that purpose came about 10 years ago.


Dr. Glenn Saxe, a child psychiatrist at Children’s Hospital Boston, scoured the records of 24 pediatric burn victims to see if he could find any link between their medications and long-term risk of PTSD. The drug that stood out was morphine, and that made some biological sense.

“Opiates reduce the activation of norepinephrine, and when you reduce norepinephrine, you should also reduce PTSD,” said neuroscientist James McGaugh of the Center for the Neurobiology of Learning and Memory at UC Irvine.

In the latest study, a team from the Naval Health Research Center in San Diego considered the treatment histories of 696 military personnel who were injured in Iraq between 2004 and 2006 and were cared for at medical facilities in the field.

A total of 243 patients went on to develop PTSD. Among that group, 60% had been treated with morphine to alleviate the pain of their injuries. Of the 453 people who did not get PTSD, 76% had received morphine.


Overall, the patients who received morphine were about half as likely to develop PTSD compared with those who did not, said epidemiologist Troy Lisa Holbrook, who led the study.

Because painful events are more likely to be traumatizing, the most logical conclusion could be that morphine worked by decreasing patients’ pain, Holbrook and her colleagues wrote. But the results also support the theory that morphine can affect the way memories are encoded, they wrote.

In the civilian world, researchers have tested other drug candidates for preemptive treatment -- including the beta blocker propranolol and the epilepsy drug gabapentin -- by comparing them with placebos. (It would not be ethical to withhold morphine from a patient who needed it for pain relief.) The drugs did not seem to help in these small clinical trials, though the researchers say their results could be a result of delay in getting the drugs to patients. In the military study, more than 70% of patients who got morphine received it within an hour.

“We can’t get to people for four to six hours,” said Dr. Roger K. Pitman of Harvard Medical School, who has conducted studies of possible PTSD interventions among trauma patients brought to the ER. “That’s probably a big obstacle we cannot overcome.”


There are also ethical issues. Fear is an important emotion, and tinkering with the potentially life-saving instinct to avoid places and situations associated with past traumas could be dangerous, Saxe said.

But an effective drug would not erase traumatic memories, just reduce their emotional intensity into the normal range, said Erik Parens, a senior research scholar at the Hastings Center, a bioethics research institute in Garrison, N.Y.

“If the treatment is safe and effective, it would be unethical to refuse it to a patient,” he said.