Subanesthetic doses of ketamine stimulate psychosis in schizophrenia

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 13; no. 1; pp. 9 - 19
• Main Authors: Lahti, Adrienne C., Koffel, Bettylou, LaPorte, David, Tamminga, Carol A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-08-1995; Nature Publishing
• Subjects: Adult; Biological and medical sciences; Dose-Response Relationship, Drug; Double-Blind Method; Drug toxicity and drugs side effects treatment; Excitatory amino acids; Female; Glutamate; Glutamic Acid - pharmacology; Haloperidol - pharmacology; Humans; Injections, Intravenous; Ketamine; Ketamine - therapeutic use; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Psychoses, Substance-Induced; Psychosis; Schizophrenia; Schizophrenia - drug therapy; Time Factors; Psychosis; Schizophrenia; Excitatory amino acids; Ketamine; Glutamate; Human; Pathophysiology; Neuroleptic; Psychotropic; Toxicity; Dopamine antagonist; Treatment efficiency; Chemotherapy; General anesthetic; Excitatory aminoacid; Antagonist; NMDA receptor
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/0893-133X(94)00131-I

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.