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.

Affiliations

1. From the Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD

   • Adrienne C Lahti
   • , David LaPorte
   •  & Carol A Tamminga

2. The Department of Psychology, University of Maryland-Baltimore Country, Baltimore, MD

   • David LaPorte

3. The Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD

   • Bettylou Koffel

Corresponding author

Correspondence to Adrienne C Lahti.

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Publication history

DOI

https://doi.org/10.1016/0893-133X(94)00131-I