Morphine for Pain Linked to Reduced PTSD Risk in Soldiers

Pauline Anderson

January 14, 2010

January 14, 2010 (Updated January 15, 2010) — Administering morphine for pain relief to soldiers shortly after being injured on the battlefield may reduce their risk for posttraumatic stress disorder (PTSD) by up to 50%, a new study suggests.

Because PTSD is a chronic condition that is often refractory to treatment, it is important to find interventions such as morphine that protect against developing the condition, said lead study author, Troy Lisa Holbrook, PhD, Naval Health Research Center, San Diego, California.

"This allows us an early secondary prevention, which may completely eradicate the risks of an individual developing PTSD or mitigate it to some degree, and that’s important because once an individual has full-blown PTSD, he or she faces a very long treatment scenario," Dr. Holbrook told Medscape Psychiatry.

The study is published in the January 14 issue of the New England Journal of Medicine.

Injury Severity

Dr. Holbrook and colleagues examined the effect of morphine on the risk for PTSD in military personnel injured during Operation Iraqi Freedom from January 2004 to December 2006.

They used data from the US Navy–Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database, a comprehensive database of clinical records related to casualties incurred both during and outside battle.

Data included information on medications administered during early resuscitation and trauma care, dosages, route of administration, and interval between arrival at the treatment facility and initiation of treatment. Severity of injuries was assessed using the Abbreviated Injury Scale and the Injury Severity Score. The Injury Severity Score for 10% of injuries was more than 16, which constitutes a serious injury.

The current analysis included 696 injured military personnel, almost all men, who did not sustain a serious traumatic brain injury because morphine is contraindicated in such injuries.

Uncertainty Highly Stressful

Assessments of PTSD were made 1 to 24 months after the injury and were based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic criteria. Of the total sample, 243 patients had PTSD. The rates of serious injury and amputation were higher among PTSD-negative patients compared with PTSD-positive patients, with rates of 5% and 2%, respectively.

Commenting on the findings, Martin P. Paulus, MD, professor in residence, Department of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California at San Diego, said that it makes some sense that there were fewer amputations among soldiers who developed PTSD.

An amputation, he said, is a clear outcome, whereas not amputating means "a lot of uncertainty," leaving patients worrying about whether they’re going to lose an arm or a leg.

"That uncertainty is tremendously stressful," said Dr. Paulus. One of the biggest issues about PTSD is the context in which trauma occurs, he said. Research has shown that PTSD rates are higher in unpredictable vs predictable traumatic events. Combat is so traumatic because soldiers never know exactly when something is going to happen, said Dr. Paulus.

Injuries sustained by both PTSD-positive and PTSD-negative patients in the study were from improvised explosive devices, gunshots, grenades, mortar, and rocket-propelled grenades.

Morphine use was common in both groups, with rates of 61% for PTSD-positive individuals and 76% in PTSD-negative patients. Doses were highly standardized, with a median dose of 5 mg and 55% of all doses between 2 and 5 mg. The route of administration was intravenous in 98% of patients.

The investigators found that morphine use during resuscitation and early trauma care was significantly associated with a reduced risk for PTSD (odds ratio, 0.47).

Using various statistical models, the researchers also found that the association remained after adjusting for age, amputation status, mechanism of injury, presence or absence of mild traumatic brain injury, and score on the Glasgow Coma Scale

Preventing Memory Consolidation

There are several theories about how pain-relieving agents may protect against PTSD. The researchers speculate that opiates may interfere with or prevent memory consolidation through a β-adrenergic mechanism.

This study is important because PTSD has significant and enduring personal, social, and economic costs, said Dr. Holbrook.

Because the study was observational, no conclusions about cause and effect could be made. Another limitation was that some data on medication were missing or incomplete. Because the doses of morphine were highly standardized, the researchers were unable to address the question of a dose-response relationship between morphine and PTSD risk.

The protective effects would probably be seen with related opiates, said Dr. Holbrook. She and her colleagues plan to continue to investigate morphine and similar compounds, as well as benzodiazepines, in individuals exposed to trauma. One study is investigating whether early treatment with opiates affects long-term quality-of-life outcomes in injured service members.

Although the current study demonstrates that morphine may help prevent the development of PTSD among injured soldiers, it does not address what happens to people who experience severe psychological trauma but who are not physically injured, said Dr. Paulus.

"Most cases of PTSD trauma are psychological events; certainly medical issues can occur, but that’s not necessary nor is it often the case," he added.

Memory Blocker?

Commenting on the findings, David Spiegel, MD, medical director, Stanford School of Medicine, California, who was not involved in the research, speculated that morphine may block the "consolidation" of memories.

"The idea is that morphine changes consolidation of the memory so that memories are stored without as much associated physical pain and perhaps mental distress. Storing memories this way makes them less painful when they’re retrieved," he said.

Opiates may also block physiologic arousal, he added. He pointed out that opiate addicts tend to be "very mellow," and people in pain who are taking opiates feel the pain but do not care about it.

The results of the study may have implications for emergency medicine, said Dr. Spiegel. The tendency now is to not give opiates to patients injured in an accident to keep them cognitively clear and to find out what happened to them. "These findings might change practice with the idea that if you give them some pain relief now you may help them in processing things later," he said.

The authors have disclosed no relevant financial relationships.

N Engl J Med. 2019;362:110-117.

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