SUBANESTHETIC DOSES OF KETAMINE STIMULATE PSYCHOSIS IN SCHIZOPHRENIA

We administered ketamine to schizophrenic individuals in a double-blin d, placebo-controlled design using a range of subanesthetic doses (0.1 , 0.3, and 0.5 mg/kg) to evaluate the nature, dose characteristics, ti me course, and neuroleptic modulation of N-methyl-D-aspartate (NMDA) a ntagonist 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 diso rder), not negative symptoms accounted for these changes. These ketami ne-induced psychotic symptoms were strikingly reminiscent of the subje ct's symptoms during active episodes of their illness. Results from si x patients who were retested in the same design after being neurolepti c-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-sen sitive glutamatergic transmission in brain exacerbates symptoms of sch izophrenia.