Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-13T01:13:37.325Z Has data issue: false hasContentIssue false
  • English
  • Français

Conceptually Driven Pharmacologic Approaches to Acute Trauma

Published online by Cambridge University Press:  07 November 2014

Roger K. Pitman  and
Douglas L. Delahanty
Get access Rights & Permissions [Opens in a new window]

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.

Type
Review Articles
Information
CNS Spectrums , Volume 10 , Issue 2 , February 2005 , pp. 99 - 106
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Kessler, RC, Sonnega, A, Bromet, E, Hughes, M, Nelson, CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048–1060.CrossRefGoogle ScholarPubMed
2.Kulka, RA, Schlenger, WE, Fairbank, JA, et al.Trauma and the Vietnam War Generation: Report of Findings from the National Vietnam Veterans Readjustment Study. New York, NY: Brunner/Mazel; 1990.Google Scholar
3.Norris, FH. Epidemiology of trauma: frequency and impact of different potentially traumatic events on different demographic groups. J Consult Clin Psychol. 1992;60:409–418.CrossRefGoogle ScholarPubMed
4.Resnick, HS, Kilpatrick, DG, Dansky, BS, Saunders, BE, Best, CL. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol. 1993;61:984–991.CrossRefGoogle Scholar
5.National Highway Traffic Safety Administration. Traffic Safety Facts 1997: A Compilation of Motor Vehicle Crash Data from the Fatality Analysis Reporting System and the General Estimates System. Washington, DC: National Center for Statistics and Analysis, U.S. Department of Transportation; 1998.Google Scholar
6.Blanchard, EB, Hickling, EJ, Taylor, AE, Loos, WR, Forneris, CA, Jaccard, J. Who develops PTSD from motor vehicle accidents? Behav Res Ther. 1996;34:1–10.CrossRefGoogle ScholarPubMed
7.Blanchard, EB, Hickling, EJ, Mitnick, N, Taylor, AE, Loos, WR, Buckley, TC. The impact of severity of physical injury and perception of life threat in the development of post-traumatic stress disorder in motor vehicle accident victims. Behav Res Ther. 1995;33:529–534.CrossRefGoogle ScholarPubMed
8.Resnick, HS, Kilpatrick, DG, Dansky, BS, Saunders, BE, Best, CL. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol. 1993;61:984–991.CrossRefGoogle Scholar
9.Rose, S, Bisson, J, Wessely, S. A systematic review of single-session psychological interventions (‘debriefing’) following trauma. Psychother Psychosom. 2003;72:176–184.CrossRefGoogle ScholarPubMed
10.Suzanna, RO, Jonathan, BI, Simon, WE. Psychological debriefing for preventing post traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2002;(2):CD000560.Google Scholar
11.Mayou, RA, Ehlers, A, Hobbs, M. Psychological debriefing for road traffic accident victims: three-year follow-up of a randomised controlled trial. Br J Psychiatry. 2000; 176:589–593.CrossRefGoogle ScholarPubMed
12.Parry, G. Treatment choice in psychological therapies and counseling: evidence based clinical practice guideline. U.K. Department of Health: Web site http://www.doh.gov.uk/mentalhealth/treatmentguidelines, 2001. Accessed on September, 2004.Google Scholar
13.Bryant, RA, Harvey, AG, Dang, ST, Sackville, T, Basten, C. Treatment of acute stress disorder: a comparison of cognitive-behavioral therapy and supportive counseling. J Consult Clin Psychol. 1998;66:862–866.CrossRefGoogle ScholarPubMed
14.Larkin M. Can post-traumatic stress disorder be put on hold? Lancet. 1999;354:1008.CrossRefGoogle Scholar
15.McGaugh, JL. Significance and remembrance: the role of neuromodulatory systems. Psychol Sci. 1990;1:15–25.CrossRefGoogle Scholar
16.McGaugh, JL, Roozendaal, B. Role of adrenal stress hormones in forming lasting memories in the brain. Curr Opin Neurobiol. 2002;12:205–210.CrossRefGoogle ScholarPubMed
17.Croiset, G, Nijsen, MJ, Kamphuis, PJ. Role of corticotropin-releasing factor, vasopressin and the autonomic nervous system in learning and memory. Eur J Pharmacol. 2000;405:225–234.CrossRefGoogle ScholarPubMed
18.McGaugh, JL. Memory and Emotion: The Making of Lasting Memories. New York, NY: Columbia University Press; 2003.Google Scholar
19.Gold, PE, van Buskirk, R. Facilitation of time-dependent memory processes with posttrial epinephrine injections. Behav Biol. 1975;13:145–153.CrossRefGoogle ScholarPubMed
20.Sternberg, DB, Isaacs, KR, Gold, PE, McGaugh, JL. Epinephrine facilitation of appetitive learning: attenuation with adrenergic receptor antagonists. Behav Neural Biol. 1985;44:447–453.CrossRefGoogle ScholarPubMed
21.Cahill, L, Pham, CA, Setlow, B. Impaired memory consolidation in rats produced with β-adrenergic blockade. Neurobiol Learn Mem. 2000;74:259–266.CrossRefGoogle ScholarPubMed
22.Cahill, L, Prins, B, Weber, M, McGaugh, JL. Beta-adrenergic activation and memory for emotional events. Nature. 1994;371:702–704.CrossRefGoogle ScholarPubMed
23.van Stegeren, AH, Everaerd, W, Cahill, L, McGaugh, JL, Gooren, LJ. Memory for emotional events: differential effects of centrally versus peripherally acting beta-blocking agents. Psychopharmacology (Berl). 1998;138:305–310.CrossRefGoogle ScholarPubMed
24.Davis, M. Pharmacological and anatomical analysis of fear conditioning. NIDA Res Monogr. 1990;97:126–162.Google ScholarPubMed
25.LeDoux, JE. The Emotional Brain: The Mysterious Underpinnings of Emotional Life. New York, NY: Simon & Schuster; 1996.Google Scholar
26.McIntyre, CK, Power, AE, Roozendaal, B, McGaugh, JL. Role of the basolateral amygdala in memory consolidation. Ann N Y Acad Sci. 2003;985:273–293.CrossRefGoogle ScholarPubMed
27.Liang, KC, Juler, RG, McGaugh, JL. Modulating effects of posttraining epinephrine on memory: involvement of the amygdala noradrenergic system. Brain Res. 1986;368:125–133.CrossRefGoogle ScholarPubMed
28.McGaugh, JL, McIntyre, CK, Power, AE. Amygdala modulation of memory consolidation: interaction with other brain systems. Neurobiol Learn Mem. 2002;78:539–535CrossRefGoogle ScholarPubMed
29.Pitman, RK. Post-traumatic stress disorder, hormones, and memory. Biol Psychiatry. 1989;26:221–223.CrossRefGoogle ScholarPubMed
30.Shalev, AY, Sahar, T, Freedman, S, et al.A prospective study of heart rate response following trauma and the subsequent development of posttraumatic stress disorder. Arch Gen Psychiatry. 1998;55:553–559.CrossRefGoogle ScholarPubMed
31.Bryant, RA, Harvey, AG, Guthrie, RM, Moulds, ML. A prospective study of psychophysiological arousal, acute stress disorder, and posttraumatic stress disorder. J Abnorm Psychol. 2000;109:341–334.CrossRefGoogle ScholarPubMed
32.Zatzick, D, Russo, J, Pitman, RK, Rivara, F, Jurkovich, G, Roy-Byrne, P. Reevaluating the association between emergency department heart rate and the development of posttraumatic stress disorder: A public health approach. Biol Psychiatry. 2005;57:91–95.CrossRefGoogle ScholarPubMed
33.Blanchard, EB, Hickling, EJ, Galovski, T, Veazey, C. Emergency room vital signs and PTSD in a treatment seeking sample of motor vehicle accident survivors. J Trauma Stress. 2002;15:199–204.CrossRefGoogle Scholar
34.Radnitz, CL, Hsu, L, Tirch, DD, et al.A comparison of posttraumatic stress disorder in veterans with and without spinal cord injury. J Abnorm Psychol. 1998;107:676–680.CrossRefGoogle ScholarPubMed
35.McFarlane, AC, Yehuda, R. Clinical treatment of posttraumatic stress disorder: conceptual challenges raised by recent research. Aust N Z J Psychiatry. 2000;34:940–953.CrossRefGoogle ScholarPubMed
36.Eysenck, HJ. A theory of the incubation of anxiety-fear responses. Behav Res Ther. 1968;6:309–321.CrossRefGoogle ScholarPubMed
37.Eysenck, HJ, Kelley, MJ. The interaction of neurohormones with Pavlovia A and Pavlovian B conditioning in the causation of neurosis, extinction, and incubation of anxiety. In: Davey, G, ed. Cognitive Processes and Pavlovian Conditioning in Humans. Chichester, United Kingdom: John Wiley & Sons Ltd.; 1987:251–286.Google Scholar
38.Charney, DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry. 2004;161:195–216.CrossRefGoogle ScholarPubMed
39.Shin, LM, Orr, SP, Carson, MA, et al.Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry. 2004;61:168–176.CrossRefGoogle ScholarPubMed
40.Kovacs, GL, Telegdy, G. Role of oxytocin in memory and amnesia. Pharmacol Ther. 1982;18:375–395.CrossRefGoogle ScholarPubMed
41.Shadmehr, R, Holcomb, HH. Neural correlates of motor memory consolidation. Science. 1997;277:821–825.CrossRefGoogle ScholarPubMed
42.Sacchetti, B, Lorenzini, CA, Baldi, E, Tassoni, G, Bucherelli, C. Auditory thalamus, dorsal hippocampus, basolateral amygdala, and perirhinal cortex role in the consolidation of conditioned freezing to context and to acoustic conditioned stimulus in the rat. J Neurosci. 1999;19:9570–9578.CrossRefGoogle ScholarPubMed
43.McFarlane, AC, Yehuda, R, Clark, CR. Biologic models of traumatic memories and post-traumatic stress disorder. The role of neural networks. Psychiatr Clin North Am. 2002;25:253-270, v.CrossRefGoogle ScholarPubMed
44.Pitman, RK, Orr, SP, Forgue, DF, de Jong, JB, Claiborn, JM. Psychophysiologic assessment of post-traumatic stress disorder imagery in Vietnam combat veterans. Arch Gen Psychiatry. 1987;44:970–975.CrossRefGoogle ScholarPubMed
45.Pitman, RK, Sanders, KM, Zusman, RM, et al.Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 20021;51:189–192.CrossRefGoogle Scholar
46.Vaiva, G, Ducrocq, F, Jezequel, K, et al.Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry. 2003;54:947–949.CrossRefGoogle ScholarPubMed
47.Taylor, F, Cahill, L. Propranolol for reemergent posttraumatic stress disorder following an event of retraumatization: a case study. J Trauma Stress. 2002;15:433–437.CrossRefGoogle ScholarPubMed
48.Saxe, G, Stoddard, F, Courtney, D, et al.Relationship between acute morphine and the course of PTSD in children with bums. J Am Acad Child Adolesc Psychiatry. 2001;40:915–921.CrossRefGoogle Scholar
49.Introini-Collison, IB, Castellano, C, McGaugh, JL. Interaction of GABAergic and beta-noradrenergic drugs in the regulation of memory storage. Behav Neural Biol. 1994;61:150–155.CrossRefGoogle ScholarPubMed
50.Gelpin, E, Bonne, O, Peri, T, Brandes, D, Shalev, AY. Treatment of recent trauma survivors with benzodiazepines: a prospective study. J Clin Psychiatry. 1996;57:390–394.Google ScholarPubMed
51.Mauri, M, Sinforiani, E, Bono, G, et al.Memory impairment in Cushing's disease. Acta Neurol Scand. 1993;87:52–55.CrossRefGoogle ScholarPubMed
52.Newcomer, JW, Selke, G, Melson, AK, et al.Decreased memory performance in healthy humans induced by stress-level cortisol treatment. Arch Gen Psychiatry. 1999;56:527–533.CrossRefGoogle ScholarPubMed
53.Kirschbaum, C, Wolf, OT, May, M, Wippich, W, Hellhammer, DH. Stress- and treatmentinduced elevations of cortisol levels associated with impaired declarative memory in health adults. Life Sci. 1996;58:1475–1483.CrossRefGoogle Scholar
54.Munck, A, Guyre, PM, Holbrook, NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984;5:25–44.CrossRefGoogle ScholarPubMed
55.Ursin, H, Olff, M. Psychobiology of coping and defence strategies. Neuropsychobiology. 1993;28:66–71.CrossRefGoogle ScholarPubMed
56.Yehuda, R, Harvey, P. Relevance of neuroendocrine alterations in PTSD to memory-related impairments of trauma survivors. In: Read, JD, Lindsay, DS, eds. Recollection of Trauma. New York, NY: Plenum Press; 1997:221–252.CrossRefGoogle Scholar
57.Yehuda, R, McFarlane, AC, Shalev, AY. Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event. Biol Psychiatry. 1998;44:1305–1313.CrossRefGoogle ScholarPubMed
58.Pacak, K, Palkovits, M, Kopin, IJ, Goldstein, DS. Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympatho-adrenal activity: in vivo microdialysis studies. Front Neuroendocrinol 1995;16:89–150.CrossRefGoogle Scholar
59.Yehuda, R. Post-traumatic stress disorder. N Engl J Med. 2002;346:108–114.CrossRefGoogle ScholarPubMed
60.Bohus, B. Endocrine influence on disease outcome: experimental findings and implications. J Psychosom Res. 1984;28:429–438.CrossRefGoogle Scholar
61.Borrell, J, De Kloet, ER, Versteeg, DH, Bohus, B. Inhibitory avoidance deficit following short-term adrenalectomy in the rat: the role of adrenal catecholamines. Behav Neural Biol. 1983;39:241–258.CrossRefGoogle ScholarPubMed
62.McFarlane, AC, Atchison, M, Yehuda, R. The acute stress response following motor vehicle accidents and its relation to PTSD. Ann N Y Acad Sci. 1997;821:437–441.CrossRefGoogle ScholarPubMed
63.Delahanty, DL, Raimonde, AJ, Spoonster, E. Initial posttraumatic urinary cortisol levels predict subsequent PTSD symptoms in motor vehicle accident victims. Biol Psychiatry. 2000;48:940–947.CrossRefGoogle ScholarPubMed
64.Schelling, B, Stoll, C, Kapfhammer, HP, et al.The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder and health-related quality of life in survivors. Crit Care Med. 1999:27:2678–2683.CrossRefGoogle ScholarPubMed
65.Schelling, G, Briegel, J, Roozendaal, B, Stoll, C, Rothenhausler, H, Kapfhammer, H. The effect of stress doses of hydrocortisone during septic shock on posttraumatic stres disorder in survivors. Biol Psychiatry. 2001;50:978–985.CrossRefGoogle Scholar
66.Schelling, G, Kilger, E, Roozendaal, B. Stress doses of hydrocortisone, trauamatic stress, and symptoms of posttraumatic stress disorder in patients after cardiac surgery: a randomized trial. Biol Psychiatry. 2004;55:627–633.CrossRefGoogle Scholar
67.Iancu, I, Rosen, Y, Moshe, K. Antiepileptic drugs in posttraumatic stress disorder. Clin Neuropharmacol. 2002;25:225–229.CrossRefGoogle ScholarPubMed
68.Sapolsky, RM. Why stress is bad for your brain. Science. 1996;273:749–50.CrossRefGoogle ScholarPubMed
69.Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000;57:925–935.CrossRefGoogle ScholarPubMed
70.Zhang, YM, Yang, Q, Xu, CT, Li, KS, Li, WQ. Effects of phenytoin on morphology and structure of hippocampal CA3 pyramidal neurons of rats in chronic stress. Acta Anaesthesiol Sin. 2003;24:403–407.Google ScholarPubMed
71.Conrad, CD, Galea, LA, Kuroda, Y, McEwen, BS. Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav Neurosci. 1996;110:1321–1334.CrossRefGoogle Scholar
72.Weisaeth, L. Acute posttraumatic stress: nonacceptance of early intervention. J Clin Psychiatry. 2001;62(suppl 17):35–40.Google ScholarPubMed
73.Morgan, CA, Krystal, JH, Southwick, SM. Toward early pharmacological posttraumatic stress intervention. Biol Psychiatry. 2003;53:834–843.CrossRefGoogle ScholarPubMed