Subanesthetic doses of ketamine stimulate psychosis in schizophrenia.
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.
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA.
A C
AC
Lahti
B
B
Koffel
D
D
LaPorte
C A
CA
Tamminga
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011605:Psychoses, Substance-Induced; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors
D018698:Glutamic Acid; D007649:Ketamine; D006220:Haloperidol