[Pharmacological modulation of the effects induced by ketamine at subanesthetic doses]

The similarity between ketamine effects and endogenous psychoses has created interest in the capacity of antipsychotic medications to block ketamine effects. In healthy subjects, a sub-anaesthetic single dose of lorazepam, typical neuroleptics, such as haloperidol, and atypical neuroleptics, such as clozapine and olanzapine, failed to block ketamine-induced positive and negative symptoms resembling schizophrenia. However, haloperidol is able to decrease ketamine-induced impairment in executive cognitive functions. Recently, lamotrigine reduced ketamine-induced psychotic symptoms, perceptual alterations, and cognitive impairments. In schizophrenic subjects, single doses of olanzapine do not decrease the effects of ketamine. However, long term treatment with clozapine has been reported to decrease ketamine-induced positive symptoms. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.