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Can medications prevent PTSD after trauma?
Recently I read press reports from the 69th annual meeting of the American Psychosomatic Society describing a study from Kent State University that found that the immediate use of hydrocortisone in persons who had just experienced a traumatic event reduced the incidence of PTSD symptoms three months after the incident. 1
Having worked with a number of people affected with PTSD, I was excited by these findings, even though they are preliminary in nature. I have seen PTSD ruin patients' lives in spite of their receiving standard treatments.
I can remember a patient named Jeff (not his real name) whom I treated a few years ago. He was a 56-year-old retired career veteran of the Vietnam War, a man whose entire identity was based on his military career. In fact, the first words he said to me were, “I am a warrior.”
Jeff had suffered PTSD symptoms for decades. I recall him describing how, “just the other night, I heard a noise outside of my home, went out in my pajamas and crawled the perimeter to look for the enemy.” PTSD ruined this unfortunate man's life. He was unable to work, to function as a husband and father, and was severely addicted to alcohol.
It is estimated that up to eight percent of the American population suffers from PTSD at any given time. That represents an enormous emotional and financial burden not only those who suffer symptoms, but on those around them-their families, friends, and society. And, those individuals with PTSD are at risk for comorbid somatic disorders that involve immune and inflammatory processes such as such as metabolic syndrome, rheumatoid arthritis, psoriasis and thyroid disease.2
Best practice for PTSD treatment includes the combination of SSRI antidepressants like Paxil and Zoloft with cognitive behavioral therapies designed specifically for PTSD. However, I believe that even this is inadequate to treat people like Jeff.
The study from Kent State suggested to me that there might be a preventive approach to the problem. If true, then the use of a regimen of 20 mg of hydrocortisone twice daily for ten days, initiated within 12 hours of hospital admission following a traumatic event might keep patients from developing the disorder altogether.
I reviewed the literature to put this study into context.
The Neurobiology of PTSD
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| ABOUT THE AUTHOR William M. Glazer, MD, is President of Glazer Medical Solutions of Key West, Fla., and Menemsha, Mass. He is a clinician, researcher, lecturer, and consultant, and has been a member of faculty of the departments of psychiatry at the Yale and Harvard schools of medicine. |
Researchers have identified two hormone systems that constitute the primary stress pathways:
The hypothalamic-pituitary-adrenal (HPA) axis is a complex set of interactions between the brain (the hypothalamus and the pituitary gland) and the adrenal glands that results in the release of glucocorticoids, which include hydrocortisone (cortisol). The HPA axis helps regulate things such as your temperature, digestion, immune system, mood, sexuality, energy and, most importantly, stress.
The sympathetic-adrenal-medullary (SAM) system is a part of the body's sympathetic nervous system, which includes a vast network of nerves originating in the spine and communicating to various organ systems throughout the body. The SAM system refers to the part of the sympathetic nervous system that regulates the release of catecholamines (epinephrine and norepinephrine) from the medullary cortex of the adrenal gland. The SAM system is best known for mediating the body's “fight or flight” response to stress.
Normally, when anyone is exposed to significant stress, the “stress hormones” from these two systems kick into gear. It is thought that for certain people, abnormalities in these systems may be associated with risk for PTSD.3 To explore this theory, researchers have intervened in the HPA and SAM systems in the hope of modifying these abnormalities.
Secondary Prevention Strategies
A 2002 study by Pitman et al. targeted the catecholamine response from the SAM system with propranolol, a blocker of norepinephrine in the brain4. Their preliminary work suggested that propranolol treatment might prevent PTSD by altering the memory-enhancing effects of emotional arousal in affected adults.
The study of hydrocortisone was an attempt to intervene on abnormalities in the HPA axis that were thought to lead to PTSD.
In an interview with the lead author of that more recent study, Douglas L. Delahanty, PhD, from the Department of Psychology at Kent State University, I learned more details. In collaboration with emergency room staff from at Summa Health System hospitals in nearby Akron, Ohio, Delahanty's team performed a randomized, double-blind study.
Patients presenting to the emergency room immediately following the experience of a severe, life-threatening trauma (e.g., auto accident, fall, physical assault) were randomly assigned to one of two conditions. Thirty-one patients received a 10-day regimen of hydrocortisone (20 mg, twice per day), while 35 patients received a placebo.
Later, at intervals of one month and three months after the traumatic event, patients were interviewed in their homes. Following the three-month interview, 14 percent of the placebo-treated group were diagnosed with PTSD, but no one in the hydrocortisone-treated group received that diagnosis. In addition, the group that received hydrocortisone treatment reported significantly fewer symptoms of PTSD and depression and better quality-of-life scores.
“Our data indicate that hydrocortisone treatment may be particularly effective in those without a history of mental health treatment,” said Delahanty.
Normally, individuals who experience a traumatic event revisit the memories of that event and “reconsolidate” them during the days and weeks that follow.
Why would hydrocortisone treatment help prevent PTSD symptoms?
Normally, individuals who experience a traumatic event revisit the memories of that event and “reconsolidate” them during the days and weeks that follow. This process occurs until the victim formulates a narrative for these memories that makes them more acceptable to live with.
Individuals at risk for PTSD are unable to perform this reconsolidation process. During the days and weeks that follow their traumatic experiences, they struggle unsuccessfully to make sense of their memories of the trauma. It is thought that this occurs, basically, because these individuals have an exaggerated sympathetic (SAM system) response and lower-than-normal levels of cortisol (HPA axis) at the time of the event.
“We think that the hydrocortisone administered for ten days disrupts this abnormal pattern in some persons who are at risk to develop PTSD,” said Delahanty. “We think that low-dose hydrocortisone works by impairing memory formation and retrieval in the hippocampus. Hydrocortisone treatment disrupts the aberrant cycle of retrieval and reconsolidation that would lead to fragmented memory.”
Delahanty pointed out that the glucocorticoids are known to alter memory performance. “We do not think that hydrocortisone treatment erases memories like you see in some movies. Rather, it impacts the person's ability to reconsolidate the painful memories so that they can come to terms with the event rather than go on to develop PTSD.”
Delahanty was quick to point out that there are other equally plausible explanations for the mechanisms that underlie the results of this PTSD study.
Thaddeus Pace, PhD, Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Emory University's School of Medicine, suggested an alternate explanation for the mechanisms that underlie the Delahanty study findings. Dr. Pace and his colleagues have been studying the role of inflammation in the development of PTSD.2
“If you change the HPA or SAM systems, you are bound to affect inflammatory mechanisms,” said Pace in an interview. While he said that “the hydrocortisone effect described by Delahanty made perfect sense to me, my explanation is different. It is plausible that the effect of hydrocortisone treatment is to tame an ‘angry’ immune system,” he asserted. “That might be a major reason why people develop PTSD in the first place.”
Inflammatory immune factors like interleukin-6 are produced by immune cells (such as macrophages and monocytes) located in the body's circulatory system, in all organs, and particularly in fat. Pace explained, “I wouldn't be surprised to see interleukin-6 levels elevated in these patients within hours after they experienced the trauma, and then remaining elevated in the persons at risk for PTSD on the third day after trauma.”
Though Delahanty's group was not set up to measure inflammatory responses in among its trauma subjects, Dr. Pace's idea is testable, and should be explored in future work.
The bottom line
Studies like that of Delahanty et al. hint that medications might provide a secondary intervention to prevent PTSD in adults exposed to trauma, specifically hydrocortisone in the case of the HPA stress pathway and propranolol in the SAM system pathway. The inflammatory response is another dimension that needs to be considered in this complex equation.
Future studies will be needed before these treatments are accepted generally, but this research provides hope that we will understand the mechanisms underlying PTSD and reduce its rate of occurrence in the near future.
Reference
- Delahanty et al: American Psychosomatic Society (APS) 69th Annual Scientific Meeting: Abstract 1755 !.Presented March 10, 2011. https://www.medscape.com/viewarticle/739500)
- Pace TWW and Heim CM:A short review on the psychoneuroimmunology of posttraumatic stress disorder: From risk factors to medical comorbidities. Brain, Behavior, and Immunity 25 (2011) 6-13
- Yehuda R., 2009. Status of glucocorticoid alterations in post-traumatic stress disorder. Ann. NY Acad. Sci. 1179, 56-69
- Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002 Jan 15; 51 (2): 189-92
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