Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

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.

Ketamine-Enhanced Psychotherapy: Preliminary Clinical Observations on its Effects in Treating Death Anxiety

“…There was also an intriguing study at the University of Cambridge in the UK, in which ketamine was used to treat compulsive behavior in young women with anorexia nervosa with good results, although the publication of this study does not clearly indicate that the clinicians used a psychotherapeutic model (Mills, Park, Manara, & Merriman, 1998.) The study used infusions of ketamine to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment.…”

Has psychiatry tamed the “ketamine tiger?” Considerations on its use for depression and anxiety

“…However, some literature exists for ketamine in other psychiatric situations. In an early and rather interesting data collection, Mills et al (1998) administered serial ketamine infusions to eating disordered patients on the theory that an NMDA antagonist would impair abnormal memories that drive eating-related compulsions. Each infusion consisted of intravenous ketamine 20 mg/ h for 10 h, and patients had serial infusions at intervals of 5-21 days.…”

Laparophobia: a cognitive perspective on appetite control in anorexia nervosa

“…In patients with a long history of eating disorder that were resistant to several other forms of treatment, Mills et al . (49) attempted infusions of 20 mg per hour ketamine for 10 h along with 20 mg twice daily nalmefene as opioid antagonist. Nine of 15 patients examined in the study showed prolonged remission when treated with two to nine ketamine‐infusion sessions at intervals of 5 days to 3 weeks.…”

“…Although amygdala circuits deal with a general category of biologically relevant stimuli (noxious, menacing), separate ventromedial prefrontal systems may be activated depending on the perceived social threat or incentive value of activities when abstaining from motivationally salient foods or engaging in obsessive regiment of training (48). Unlike LTP, which models environmental input, fear is capable of being self-perpetuated when amygdala cells are barraged by 'AN thoughts' (49) in individuals with a deficient processing of personal somatic representation rather than by the (objective) assessment of 'others'. Synaptic plasticity may plausibly underlie chronicity of AN, which is its main hazard in terms of medical complications and social consequences.…”