TY - JOUR
T1 - Subanesthetic doses of ketamine stimulate psychosis in schizophrenia
AU - Lahti, Adrienne C.
AU - Koffel, Bettylou
AU - LaPorte, David
AU - Tamminga, Carol A.
PY - 1995/8
Y1 - 1995/8
N2 - 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.
AB - 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.
KW - Excitatory amino acids
KW - Glutamate
KW - Ketamine
KW - Psychosis
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=0029162231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029162231&partnerID=8YFLogxK
U2 - 10.1016/0893-133X(94)00131-I
DO - 10.1016/0893-133X(94)00131-I
M3 - Article
C2 - 8526975
AN - SCOPUS:0029162231
SN - 0893-133X
VL - 13
SP - 9
EP - 19
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 1
ER -