Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions |
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Authors: | Mills IH; Park GR; Manara AR; Merriman RJ |
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Affiliation: | Department of Medicine, University of Cambridge, UK. |
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Abstract: | We have previously shown that eating disorders are a compulsive behaviour
disease, characterized by frequent recall of anorexic thoughts. Evidence
suggests that memory is a neocortical neuronal network, excitation of which
involves the hippocampus, with recall occurring by re-excitement of the
same specific network. Excitement of the hippocampus by glutamate-NMDA
receptors, leading to long-term potentiation (LTP), can be blocked by
ketamine. Continuous block of LTP prevents new memory formation but does
not affect previous memories. Opioid antagonists prevent loss of
consciousness with ketamine but do not prevent the block of LTP. We used
infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily
nalmefene as opioid antagonist to treat 15 patients with a long history of
eating disorder, all of whom were chronic and resistant to several other
forms of treatment. Nine (responders) showed prolonged remission when
treated with two to nine ketamine infusions at intervals of 5 days to 3
weeks. Clinical response was associated with a significant decrease in
Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after
ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients
(non-responders) the score was: before ketamine, 42.8 +/- 3.7; after
ketamine, 44.8 +/- 3.1. There was no significant response to at least five
ketamine treatments, perhaps because the compulsive drive was
re-established too soon after the infusion, or because the dose of opioid
antagonist, nalmefene, was too low.
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