Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviourdisease, characterized by frequent recall of anorexic thoughts. Evidencesuggests that memory is a neocortical neuronal network, excitation of whichinvolves the hippocampus, with recall occurring by re-excitement of thesame specific network. Excitement of the hippocampus by glutamate-NMDAreceptors, leading to long-term potentiation (LTP), can be blocked byketamine. Continuous block of LTP prevents new memory formation but doesnot affect previous memories. Opioid antagonists prevent loss ofconsciousness with ketamine but do not prevent the block of LTP. We usedinfusions of 20 mg per hour ketamine for 10 h with 20 mg twice dailynalmefene as opioid antagonist to treat 15 patients with a long history ofeating disorder, all of whom were chronic and resistant to several otherforms of treatment. Nine (responders) showed prolonged remission whentreated with two to nine ketamine infusions at intervals of 5 days to 3weeks. Clinical response was associated with a significant decrease inCompulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; afterketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients(non-responders) the score was: before ketamine, 42.8 +/- 3.7; afterketamine, 44.8 +/- 3.1. There was no significant response to at least fiveketamine treatments, perhaps because the compulsive drive wasre-established too soon after the infusion, or because the dose of opioidantagonist, nalmefene, was too low.