Effects of ketamine mimic only some of the symptoms of schizophrenia
Aug 9, 2006 - 12:36:37 PM

Ketamine can induce symptoms of referential thinking, but not other symptoms of schizophrenia, according to a new study.

Ketamine is the structural analogue of the drug phencyclidine, now considered too toxic for experimental use in humans. In healthy volunteers, phencyclidine has been reported to induce paranoia, perceptual changes and other symptoms, including disorganisation of thought, negativism, apathy, withdrawal, poverty of speech and catatonia.

The psychosis-inducing effect of ketamine is important evidence supporting the glutamate hypothesis of schizophrenia. This hypothesis, one of the leading neurochemical theories of schizophrenia, is based on the observation that glutamate antagonist drugs like ketamine induce symptoms similar to those of schizophrenia

However, the symptoms the drug produces have not been described systematically. As the effects of ketamine are currently being characterised as a model of schizophrenia, it is important to document its psychopathological effects properly.

In this study, published in the August issue of the British Journal of Psychiatry, ketamine or a placebo was administered by continuous infusion to 15 healthy volunteers on 2 occasions, separated by at least 3 weeks.

While receiving ketamine at a set level, participants were interviewed to measure psychotic and non-psychotic symptoms; speech (for assessment of thought disorder); dissociation (e.g. ‘Do you feel disconnected from your own body?’); and also the negative symptoms of schizophrenia.

It was found that ketamine induced a range of perceptual distortions, but not visual or auditory hallucinations. Nearly half the people studied showed abnormal beliefs in the form of ‘referential ideas’, or delusions e.g. “I feel like a puppet…I feel like I’m the focus. Everyone is watching me.” There were only mild and infrequent ratings of thought disorder.

The authors comment that they were unable to replicate the finding that ketamine causes substantial levels of schizophrenia’s positive symptoms. Unchanging facial expression and other symptoms of ‘affective flattening’, plus another negative symptom, poverty nof speech, were found in over half the sample, where they were usually rated as mild or moderate.

Even so, they say, it is an open question whether ketamine genuinely induces the negative symptoms of schizophrenia, as it is possible that the changes observed were simply manifestations of ketamine’s general depressant effect on the central nervous system.

In summary, this study suggests that ketamine has a limited ‘psychotomimetic’ effect, which is most convincing with respect to an ability to induce referential beliefs similar to delusions.

Although ketamine does not reproduce the full picture of schizophrenia, the drug does seem to give rise to some of the symptoms, and it may prove useful in testing theories of specific symptoms such as delusions.

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