Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 9-19 |
Number of pages | 11 |
Journal | Neuropsychopharmacology |
Volume | 13 |
Issue number | 1 |
DOIs | |
State | Published - Aug 1995 |
Keywords
- Excitatory amino acids
- Glutamate
- Ketamine
- Psychosis
- Schizophrenia
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health