Subanesthetic doses of ketamine stimulate psychosis in schizophrenia

Academic Article


  • We administered ketamine to schizophrenic individuals in a double-blind, placebo-controlled design using a range of subanesthetic doses (0.1, 0.3, and 0.5 mg/kg) to evaluate the nature, dose characteristics, time course, and neuroleptic modulation of N-methyl-D-aspartate (NMDA) antagonist action on mental status in schizophrenia. Ketamine induced a dose-related, short (< 30 minutes) worsening in mental status in the haloperidol-treated condition, reflected by a significant increase in BPRS total score for the 0.3 mg/kg (p =.005) and 0.5 mg/kg (p =.01) challenges. Positive symptoms (hallucinations, delusions, thought disorder), not negative symptoms accounted for these changes. These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject's symptoms during active episodes of their illness. Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis. Several subjects evidenced delayed or prolonged (8-24 hours) psychotomimetic effects such as worsening of psychosis with visual hallucinations. These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia. © 1995 American College of Neuropsychopharmacology.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 23216554
  • Author List

  • Lahti AC; Koffel B; Laporte D; Tamminga CA
  • Start Page

  • 9
  • End Page

  • 19
  • Volume

  • 13
  • Issue

  • 1