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Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims

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Abstract

Rationale

Ketamine, an N-methyl-d-aspartate receptor antagonist, produces transient dissociative and psychotic states in healthy humans that resemble symptoms shown by subjects with acute and chronic posttraumatic stress disorder (PTSD). Since ketamine is widely used as an analgesic and sedative in emergency care, it might be one factor triggering, modulating, or exacerbating PTSD in accident victims when given in the acute trauma phase.

Objectives

The purpose of the present study was to determine whether the peritraumatic administration of ketamine affects acute and sustained PTSD symptoms in accident victims.

Methods

A sample of 56 moderately injured accident victims was screened retrospectively for acute (Peritraumatic Dissociative Experiences Questionnaire; Acute Stress Disorder Scale) and for current PTSD symptoms (Impact of Event Scale) approximately 1 year postaccident. All subjects had received a single or fractionated dose of either racemic ketamine (n=17), (S)-ketamine (n=12), or opioids (n=27) during emergency ambulance transportation.

Results

Retrospectively assessed acute symptomatology was strongly increased in (S)-ketamine subjects in terms of dissociation, reexperiencing, and avoidance, and slightly heightened in racemic ketamines. Current PTSD symptoms were substantially elevated in (S)-ketamine subjects, while there was no difference observed between opioids and racemic ketamines. Medication groups did not differ in regard to demographic variables, previous or postaccidental traumatic events, time between accident and investigation, and injury severity.

Conclusions

The data provide first evidence for a modulating effect of a single-dose ketamine on the severity and duration of posttraumatic stress symptoms in accident victims.

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References

  • Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH (2000) Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-d-aspartate receptor antagonists. Arch Gen Psychiatry 57:270–276

    Article  PubMed  CAS  Google Scholar 

  • Atallah MM, El-Mohayman HA, El-Metwally RE (2001) Ketamine–midazolam total intravenous anaesthesia for prolonged abdominal surgery. Eur J Anaesthesiol 18:29–35

    Article  PubMed  CAS  Google Scholar 

  • Baker SP, O'Neill B, Haddon W, Long WB (1974) The Injury Severity Score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14:187–196

    Article  PubMed  CAS  Google Scholar 

  • Bryant RA, Moulds ML, Guthrie RM (2000) Acute Stress Disorder Scale: a self-report measure of acute stress disorder. Psychol Assess 12:61–68

    Article  PubMed  CAS  Google Scholar 

  • Cartwright PD, Pingel SM (1984) Midazolam and diazepam in ketamine anesthesia. Anesthesia 39:439–442

    Article  CAS  Google Scholar 

  • Chambers RA, Bremner JD, Moghaddam B, Southwick SM, Charney DS, Krystal JH (1999) Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation. Semin Clin Neuropsychiatry 4:274–281

    PubMed  CAS  Google Scholar 

  • Cho HS, D'Souza DC, Gueorguieva R, Perry EB, Madonick S, Karper LP, Abi-Dargham A, Belger A, Abi-Saab W, Lipschitz D, Bennet A, Seibyl JP, Krystal JH (2005) Absence of behavioral sensitization in healthy human subjects following repeated exposure to ketamine. Psychopharmacology. 10.1007/s00213-004-2066-5

  • Coplan JD, Mathew SJ, Smith ELP, Trost RC, Scharf BA, Martinez J, Gorman JM, Monn JA, Schoepp DD, Rosenblum LA (2001) Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhumane primate hypothalamic–pituitary–adrenal axis and noradrenergic function. CNS Spectr 6:607–617

    PubMed  CAS  Google Scholar 

  • Haberny KA, Paule MG, Scallet AC, Sistare FD, Lester DS, Hanig JP, Slikker W (2002) Ontogeny of the N-methyl-d-aspartate (NMDA) receptor system and susceptibility to neurotoxicity. Toxicol Sci 68:9–17

    Article  PubMed  CAS  Google Scholar 

  • Harvey BH, Oosthuizen F, Brand L, Wegener G, Stein DJ (2004) Stress–restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus. Psychopharmacology 175:494–502

    Article  PubMed  CAS  Google Scholar 

  • Hertzberg MA, Butterfield MI, Feldman ME, Beckham JC, Sutherland SM, Connor KM, Davidson JR (1999) A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biol Psychiatry 45:1226–1229

    Article  PubMed  CAS  Google Scholar 

  • Kniest A, Wiesenberg C, Weber B, Colla M, Heuser I, Deuschle M (2001) The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus–pituitary–adrenocortical system in elderly subjects. Neuropsychobiology 43:91–95

    Article  PubMed  CAS  Google Scholar 

  • Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51:199–214

    PubMed  CAS  Google Scholar 

  • Krystal JH, Karper LP, Bennett A, D'Souza CD, Abi-Dargham A, Morrissey K, Abi-Saab D, Bremner JD, Bowers MB Jr, Suckow RF, Stetson P, Heninger GR, Charney DS (1998) Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology 135:213–229

    Article  PubMed  CAS  Google Scholar 

  • Krystal JH, D'Souza DC, Mathalon D, Perry E, Belger A, Hoffman R (2003) NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology 169:215–233

    Article  PubMed  CAS  Google Scholar 

  • Koopman C, Sephton S, Abercrombie HC, Classen C, Butler LD, Gore-Felton C, Borggrefe A, Spiegel D (2003) Dissociative symptoms and cortisol responses to recounting traumatic experiences among childhood sexual abuse survivors with PTSD. J Trauma & Dissociation 4:29–44

    Article  Google Scholar 

  • Kubany ES, Haynes SN, Beth Leisen M, Owens JA, Kaplan AS, Watson SB, Burns K (2000) Development and preliminary validation of a brief broad-spectrum measure of trauma exposure: the Traumatic Life Events Questionnaire. Psychol Assess 12:210–224

    Article  PubMed  CAS  Google Scholar 

  • Marmar CR, Weiss DS, Metzler T (1998) Peritraumatic dissociation and posttraumatic stress disorder. In: Bremner JD, Marmar CR (eds) Trauma, memory, and dissociation. American Psychiatric Press, Washington DC, pp 229–252

    Google Scholar 

  • Makatsori A, Duncko R, Moncek F, Loder I, Katina S, Jezova D (2004) Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by the glutamate release-inhibiting drug lamotrigine. Neuroendocrinology 79:34–42

    Article  PubMed  CAS  Google Scholar 

  • Morgan CJ, Mofeez A, Brandner B, Bromley L, Curran HV (2004) Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers. Neuropsychopharmacology 29:208–218

    Article  PubMed  CAS  Google Scholar 

  • Newcomer JW, Selke G, Melson AK, Hershey T, Craft S, Richards K, Alderson AL (1999) Decreased memory performance in healthy humans induced by stress-level cortisol treatment. Arch Gen Psychiatry 56:527–533

    Article  PubMed  CAS  Google Scholar 

  • Ozer EJ, Weiss DS, Best SR, Lipsey TL (2003) Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull 129:52–73

    Article  PubMed  Google Scholar 

  • Saxe G, Stoddard F, Courtney D, Cunningham K, Chawla N, Sheridan R, King D, King L (2001) Relationship between acute morphine and the course of PTSD in children with burns. J Am Acad Child Adolesc Psych 40:915–921

    Article  CAS  Google Scholar 

  • Takahata R, Moghaddam B (2003) Activation of glutamate neurotransmission in the prefrontal cortex sustains the motoric and dopaminergic effects of phencyclidine. Neuropsychopharmacology 28:1117–1124

    PubMed  CAS  Google Scholar 

  • Vollenweider FX, Leenders KL, Oye I, Hell D, Angst J (1997) Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET). Eur Neuropsychopharmacol 7:25–38

    Article  PubMed  CAS  Google Scholar 

  • Vollenweider FX, Vontobel P, Oye I, Hell D, Leenders KL (2000) Effects of (S)-ketamine on striatal dopamine: a [c]raclopride PET study of a model psychosis in humans. J Psychiatr Res 34:35–43

    Article  PubMed  CAS  Google Scholar 

  • Weiss D, Marmar C (1997) The Impact of Event Scale-Revised. In: Wilson J, Keane T (eds) Assessing psychological trauma and PTSD. Guildford, New York

    Google Scholar 

  • White PF (1982) Comparative evaluation of intravenous agents for rapid sequence induction—thiopental, ketamine, and midazolam. Anesthesiology 57:279–284

    Article  PubMed  CAS  Google Scholar 

  • Winter H, Irle E (2004) Hippocampal volume in adult burn patients with and without posttraumatic stress disorder. Am J Psychiatr 161:2194–2200

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Physiological Psychology, Tübingen University, Gartenstr. 29, 72074, Tübingen, Germany

    Michael Schönenberg, Ursula Reichwald & Martin Hautzinger

  2. Department of Psychiatry and Psychotherapy, Rostock University, Rostock, Germany

    Gregor Domes

  3. Berufsgenossenschaftliche Unfallklinik Tübingen, Tübingen, Germany

    Andreas Badke

Authors
  1. Michael Schönenberg
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  2. Ursula Reichwald
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  3. Gregor Domes
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  4. Andreas Badke
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  5. Martin Hautzinger
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Correspondence to Michael Schönenberg.

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Schönenberg, M., Reichwald, U., Domes, G. et al. Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims. Psychopharmacology 182, 420–425 (2005). https://doi.org/10.1007/s00213-005-0094-4

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  • DOI: https://doi.org/10.1007/s00213-005-0094-4

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