CNS Drugs

, Volume 18, Issue 6, pp 343–354 | Cite as

Depersonalisation Disorder

A Contemporary Overview
  • Daphne Simeon
Therapy In Practice


Depersonalisation disorder is characterised by prominent depersonalisation and often derealisation, without clinically notable memory or identity disturbances. The disorder has an approximately 1: 1 gender ratio with onset at around 16 years of age. The course of the disorder is typically long term and often continuous. Mood, anxiety and personality disorders are often comorbid with depersonalisation disorder but none predict symptom severity.

The most common immediate precipitants of the disorder are severe stress, depression and panic, and marijuana and hallucinogen ingestion. Depersonalisation disorder has also been associated with childhood interpersonal trauma, in particular emotional maltreatment.

Neurochemical findings have suggested possible involvement of serotonergic, endogenous opioid and glutamatergic NMDA pathways. Brain imaging studies in depersonalisation disorder have revealed widespread alterations in metabolic activity in the sensory association cortex, as well as prefrontal hyperactivation and limbic inhibition in response to aversive stimuli. Depersonalisation disorder has also been associated with autonomic blunting and hypothalamic-pituitary-adrenal axis dysregulation.

To date, treatment recommendations and guidelines for depersonalisation disorder have not been established. There are few studies assessing the use of pharmacotherapy in this disorder. Medication options that have been reported include clomipramine, fluoxetine, lamotrigine and opioid antagonists. However, it does not appear that any of these agents have a potent anti-dissociative effect. A variety of psychotherapeutic techniques has been used to treat depersonalisation disorder (including trauma-focused therapy and cognitive-behavioural techniques), although again none of these have established efficacy to date. Overall, novel therapeutic approaches are clearly needed to help individuals experiencing this refractory disorder.


Lamotrigine Naltrexone Temporal Lobe Epilepsy Opioid Antagonist Borderline Personality Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This manuscript was supported in part by the NIMH, grant number: MH62414 awarded to Dr Simeon. The author has no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Aderibigbe YA, Bloch RM, Waler WR. Prevalence of depersonalization and derealization experiences in a rural population. Soc Psychiatry Psychiatr Epidemiol 2001; 36: 63–9PubMedCrossRefGoogle Scholar
  2. 2.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washingon, DC: American Psychiatric Association, 1994Google Scholar
  3. 3.
    Ross CA. Epidemiology of multiple personality disorder and dissociation. Psych Clin N Amer 1991; 14: 503–17Google Scholar
  4. 4.
    Simeon D, Gross S, Guralnik O, et al. Feeling unreal: 30 cases of DSM-III depersonalization disorder. Am J Psychiatry 1997 Aug; 154(8): 1107–13PubMedGoogle Scholar
  5. 5.
    Simeon D, Knutelska M, Nelson D, et al. Feeling unreal: a depersonalization disorder update of 117 cases. J Clin Psychiatry 2003; 64(9): 990–7PubMedCrossRefGoogle Scholar
  6. 6.
    Baker D, Hunter E, Lawrence E, et al. Depersonalisation disorder: clinical features of 204 cases. Br J Psychiatry 2003; 182: 428–33PubMedCrossRefGoogle Scholar
  7. 7.
    Sierra M, Berrios GE. The phenomenological stability of depersonalization: comparing the old with the new. J Nerv Ment Dis 2001; 189: 629–36PubMedCrossRefGoogle Scholar
  8. 8.
    Medford N, Baker D, Hunter E, et al. Chronic depersonalization following illicit drug use: a controlled analysis of 40 cases. Addiction 2003; 98: 1731–6PubMedCrossRefGoogle Scholar
  9. 9.
    Guralnik O, Schmeidler J, Simeon D. Feeling unreal: cognitive processes in depersonalization. Am J Psychiatry 2000; 157: 103–9PubMedGoogle Scholar
  10. 10.
    van Ijzendoorn MH, Schuengel C. The measurement of dissociation in normal and clinical populations: meta-analytic validation of the Dissociative Experiences Scale (DES). Clin Psychol Rev 1996; 16: 365–82CrossRefGoogle Scholar
  11. 11.
    Simeon D, Guralnik O, Schmeidler J, et al. The role of childhood interpersonal trauma in depersonalization disorder. Am J Psychiatry 2001 Jul; 158(7): 1027–33PubMedCrossRefGoogle Scholar
  12. 12.
    Butler LD, Duran RE, Jasiukaitis P, et al. Hypnotizability and traumatic experience: a diathesis-stress model of dissociative symptomatology. Am J Psychiatry 1996; 153(7 Suppl.): 42–63PubMedGoogle Scholar
  13. 13.
    Waller NG, Ross CA. The prevalence and biometric structure of pathological dissociation in the general population: taxometric and behavior genetic findings. J Abnorm Psychol 1997; 106: 499–510PubMedCrossRefGoogle Scholar
  14. 14.
    Jang KL, Paris J, Zweig-Frank H, et al. Twin study of dissociative experience. J Nerv Ment Dis 1998 Jun; 186(6): 345–51PubMedCrossRefGoogle Scholar
  15. 15.
    Curran HV, Morgan C. Cognitive, dissociative, and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later. Addiction 2000; 95: 575–90PubMedCrossRefGoogle Scholar
  16. 16.
    Anand A, Charney D, Oren D, et al. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Arch Gen Psychiatry 2000 Mar; 57(3): 270–6PubMedCrossRefGoogle Scholar
  17. 17.
    Feigenbaum JJ, Bergmann F, Richmond SA, et al. Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker. Proc Natl Acad Sci U S A 1989 Dec; 86(23): 9584–7PubMedCrossRefGoogle Scholar
  18. 18.
    Szymanski HV. Prolonged depersonalization after marijuana use. Am J Psychiatry 1981 Feb; 138(2): 231–3PubMedGoogle Scholar
  19. 19.
    Keshaven MS, Lishman WA. Prolonged depersonalization following cannabis abuse. Br J Addict 1986 Feb; 81(1): 140–2PubMedCrossRefGoogle Scholar
  20. 20.
    Torch EM. Review of the relationship between obsession and depersonalization. Acta Psychiatr Scand 1978; 58: 191–8PubMedCrossRefGoogle Scholar
  21. 21.
    Simeon D, Hollander E, Stein DJ, et al. Induction of depersonalization by the serotonin agonist meta-chlorophenylpiperazine. Psychiatry Res 1995 Sep 29; 58(2): 161–4PubMedCrossRefGoogle Scholar
  22. 22.
    Southwick SM, Krystal JH, Bremner JD, et al. Noradrenergic and serotonergic function in posttraumatic stress disorder. Arch Gen Psychiatry 1997 Aug; 54(8): 749–58PubMedCrossRefGoogle Scholar
  23. 23.
    Madden J, Akil H, Patrick RL, et al. Stress-induced parallel changes in central opioid levels and pain responsiveness in the rat. Nature 1977 Jan; 265(5592): 358–60PubMedCrossRefGoogle Scholar
  24. 24.
    Pitman RK, Van der Kolk BA, Orr SP, et al. Naloxone-reversible analgesic response to combat-related stimuli in posttraumatic stress disorder: a pilot study. Arch Gen Psychiatry 1990 Jun; 47(6): 541–4PubMedCrossRefGoogle Scholar
  25. 25.
    Walsh SL, Geter-Douglas B, Strain EC, et al. Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans. J Pharmacol Exp Ther 2001 Oct; 299(1): 147–58PubMedGoogle Scholar
  26. 26.
    Bohus MJ, Landwehrmeyer B, Stiglmayr CE, et al. Naltrexone in the treatment of dissociative symptoms in patients with borderline personality disorder: a open-label trial. J Clin Psychiatry 1999 Sep; 60(9): 598–603PubMedCrossRefGoogle Scholar
  27. 27.
    Nuller YL, Morozova MG, Kushnir ON, et al. Effect of naloxone therapy on depersonalization: a pilot study. J Psychopharmacol 2001; 15(2): 93–5PubMedCrossRefGoogle Scholar
  28. 28.
    Glover H. A preliminary trial of nalmefene for the treatment of emotional numbing in combat veterans with post-traumatic stress disorder. Isr J Psychiatry Relat Sci 1993; 30(4): 255–63PubMedGoogle Scholar
  29. 29.
    Griffin MG, Resick PA, Mechanic MB. Objective assessment of peritraumatic dissociation: psychophysiological indicators. Am J Psychiatry 1997 Aug; 154(8): 1081–8PubMedGoogle Scholar
  30. 30.
    Sierra M, Senior C, Dalton J, et al. Autonomie response in depersonalization disorder. Arch Gen Psychiatry 2002 Sep; 59(9): 833–8PubMedCrossRefGoogle Scholar
  31. 31.
    Southwick SM, Bremner JD, Rasmusson A, et al. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry 1999 Nov; 46(9): 1192–204PubMedCrossRefGoogle Scholar
  32. 32.
    Simeon D, Guralnik O, Knutelska M, et al. Basal norepinephrine in depersonalization disorder. Psych Res 2003; 121: 93–7CrossRefGoogle Scholar
  33. 33.
    Yehuda R. Sensitization of the hypothalamic-pituitary-adrenal axis in posttraumatic stress disorder. Ann N Y Acad Sci 1997; 821: 57–75PubMedCrossRefGoogle Scholar
  34. 34.
    Simeon D, Guralnik O, Knutelska M, et al. Hypothalamic-pituitary-adrenal axis dysregulation in depersonalization disorder. Neuropsychopharmacology 2001 Nov; 25(5): 793–5PubMedCrossRefGoogle Scholar
  35. 35.
    Stanton BR, David AS, Cleare AJ, et al. Basal activity of the hypothalamic-pituitary-adrenal axis in patients with depersonalization disorder. Psychiatry Res 2001 Oct; 104(1): 85–9PubMedCrossRefGoogle Scholar
  36. 36.
    Penfield W, Rasmussen T. The cerebral cortex of man: a clinical study of localization of function. New York: MacMillan Company, 1950: 157–81Google Scholar
  37. 37.
    Sierra M, Berrios GE. Depersonalization: neurobiological perspectives. Biol Psychiatry 1998; 44: 898–908PubMedCrossRefGoogle Scholar
  38. 38.
    Sierra M, Lopera F, Lambert MV, et al. Separating depersonalization and derealisation: the relevance of the “lesion” method. J Neurol Neurosurg Psychiatry 2002; 72: 530–2PubMedGoogle Scholar
  39. 39.
    Lambert MV, Sierra M, Phillips ML, et al. The spectrum of organic depersonalization: a review plus four new cases. J Neuropsychiatry Clin Neurosci 2002; 14: 141–54PubMedCrossRefGoogle Scholar
  40. 40.
    Krystal J, Bremner D, Southwick SM, Charney DS. The emerging neurobiology of dissociation: implications for the treatment of posttraumatic stress disorder. In: Bremner JD, Marmar CR, editors. Trauma, memory, and dissociation. Washington, DC: American Psychiatric Press Inc, 1998Google Scholar
  41. 41.
    Devinsky O, Putnam F, Grafman J, et al. Dissociative states and epilepsy. Neurology 1989 Jun; 39(6): 835–40PubMedCrossRefGoogle Scholar
  42. 42.
    Ackner B. Depersonalization: I. Etiology and phenomenology: II. clinical syndromes. J Ment Sci 1954; 100: 838–72Google Scholar
  43. 43.
    Vallar G, Perani D. The anatomy of unilateral neglect after right-hemisphere stroke lesions: a clinical/CT-scan correlation study in man. Neuropsychologia 1986; 24(5): 609–22PubMedCrossRefGoogle Scholar
  44. 44.
    Salanova V, Andermann F, Rasmussen T, et al. Parietal lobe epilepsy: clinical manifestations and outcome in 82 patients treated surgically between 1929 and 1988. Brain 1995 Jun; 118(3): 607–27PubMedCrossRefGoogle Scholar
  45. 45.
    Adolphs R, Damasio H, Tranel D, et al. A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping. J Neurosci 2000 Apr; 20(7): 2683–90PubMedGoogle Scholar
  46. 46.
    Gorno-Tempini ML, Price CJ, Josephs O, et al. The neural systems sustaining face and proper-name processing. Brain 1998 Nov; 121(11): 2103–18PubMedCrossRefGoogle Scholar
  47. 47.
    Blanke O, Ortigue S, Landis T, et al. Stimulating illusory own-body perceptions. Nature 2002 Sep; 419(6904): 269–70PubMedCrossRefGoogle Scholar
  48. 48.
    Mathew RJ, Wilson WH, Chiu NY, et al. Regional cerebral blood flow and depersonalization after tetrahydrocannibol administration. Acta Psychiatr Scand 1999; 100: 67–75PubMedCrossRefGoogle Scholar
  49. 49.
    Vollenweider FX, Vontobek P, Hell D, et al. 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man: a PET study with [11C]raclopride. Neuropsychopharmacology 1999; 20: 424–33PubMedCrossRefGoogle Scholar
  50. 50.
    Vollenweider FX, Maguire RP, Leenders KL, et al. Effects of high amphetamine dose on mood and cerebral glucose metabolism in normal volunteers using positron emission tomography (PET). Psychiatry Res 1998; 83: 149–62PubMedCrossRefGoogle Scholar
  51. 51.
    Lanius RA, Williamson PC, Boksman K, et al. Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation. Biol Psychiatry 2002 Aug; 52(4): 305–11PubMedCrossRefGoogle Scholar
  52. 52.
    Phillips ML, Medford N, Senior C, et al. Depersonalization disorder: thinking without feeling. Psychiatry Res 2001 Dec; 108(3): 145–60PubMedCrossRefGoogle Scholar
  53. 53.
    Simeon D, Guralnik O, Hazlett EA, et al. Feeling unreal: a PET study of depersonalization disorder. Am J Psychiatry 2000; 157: 1782–8PubMedCrossRefGoogle Scholar
  54. 54.
    Hollander E, Liebowitz MR, DeCaria CM, et al. Treatment of depersonalization with serotonin reuptake blockers. J Clin Psychopharmacol 1990 Jun; 10(3): 200–3PubMedCrossRefGoogle Scholar
  55. 55.
    Simeon D, Stein DJ, Hollander E. Treatment of depersonalization disorder with clomipramine. Biol Psychiatry 1998 Aug; 44(4): 302–3PubMedCrossRefGoogle Scholar
  56. 56.
    Fichtner CG, Horevitz RP, Braun BG. Fluoxetine in depersonalization disorder. Am J Psychiatry 1992 Dec; 149(12): 1750–1PubMedGoogle Scholar
  57. 57.
    Ratliff NB, Kerski D. Depersonalization treated with fluoxetine. Am J Psychiatry 1995 Nov; 152(11): 1689–90PubMedGoogle Scholar
  58. 58.
    Simeon D, Gurainik O, Schmeidler J, et al. Fluoxetine is not efficacious in depersonalisation disorders: a randomized controlled trial. Br J Psychiatry. In pressGoogle Scholar
  59. 59.
    Sierra M, Phillips ML, Lambert MV, et al. Lamotrigine in the treatment of depersonalization disorder. J Clin Psychiatry 2001 Oct; 62(10): 826–7PubMedCrossRefGoogle Scholar
  60. 60.
    Sierra M, Phillips ML, Krystal J, et al. A placebo-controlled, crossover trial of lamotrigine in depersonalization disorder. J Psychopharmacol 2003 Mar; 17(1): 103–5PubMedCrossRefGoogle Scholar
  61. 61.
    Frances A, Sacks M, Aronoff S. Depersonalization: a self-relational perspective. Int J Psychoanal 1977; 58: 325–31PubMedGoogle Scholar
  62. 62.
    Hunter ECM, Phillips ML, Chalder T, et al. Depersonalisation disorder: a cognitive-behavioural conceptualisation. Behav Res Ther 2003; 41(12): 1451–67PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA

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