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Conceptually Driven Pharmacologic Approaches to Acute Trauma

  • Roger K. Pitman and Douglas L. Delahanty

Abstract

Secondary prevention of posttraumatic stress disorder (PTSD) entails intervening in the aftermath of a traumatic event to forestall the development of PTSD. There has been little psychopharmacologic research in this area. This is surprising, given that PTSD is the mental disorder with the most clearly identified cause and onset. In a translational model of PTSD's pathogenesis presented herein: A traumatic event (unconditioned stimulus) overstimulates endogenous stress hormones (unconditioned response); these mediate an overconsolidation of the event's memory trace; recall of the event in response to reminders (conditioned stimulus); releases further stress hormones (conditioned response); these cause further overconsolidation; and the overconsolidated memory generates PTSD symptoms. Noradrenergic hyperactivity in the basolateral amygdala is hypothesized to mediate this cycle. Preventing pre-synaptic norepinephrine release with α2-adrenergic agonists or opioids, or blocking post-synaptic norepinephrine sreceptors with β-adrenergic antagonists such as propranolol, reduces hormonally enhanced memories and fear conditioning. Two controlled studies of trauma victims presenting to emergency rooms suggest that posttrauma propranolol reduces subsequent PTSD, as does one naturalistic clinical study of morphine treatment of burned children. Cortisol both enhances memory consolidation and reduces memory retrieval, leading to mixed predictions. Two controlled studies of intensive care unit patients found that cortisol reduced PTSD. One study did not find benzodiazepines effective in preventing PTSD. Selective serotonin reuptake inhibitors, antiepileptics, and α2-adrenergic agonists have yet to be tried.

Copyright

Corresponding author

Please direct all correspondence to: Roger K. Pitman, MD, Massachusetts General Hospital, Room 2616, Bldg. 149, 13th Street, Charlestown, MA 02129; Tel: 617-726-5333, Fax: 617-726-4078; E-mail: roger_pitman@hms.harvard.edu.

References

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Conceptually Driven Pharmacologic Approaches to Acute Trauma

  • Roger K. Pitman and Douglas L. Delahanty

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