Anesthesia Drugs May Relieve Depression in Some

A pilot study has found that repeated low doses of the anesthesia drug ketamine produced almost immediate relief from depression in patients with treatment-resistant depression (TRD) who did not respond to any other type of depression therapy.

Researchers at Mount Sinai School of Medicine (New York, NY, USA) and the University of Groningen (The Netherlands) studied the effects of repeated doses of ketamine in 10 medication-free symptomatic patients with TRD, who had previously shown a meaningful antidepressant response to a single dose of the drug. The study protocol involved six intra-venous (IV) infusions of ketamine over 12 days; on day 1, the patients received a 40-min infusion of ketamine (0.5 mg/kg), in an inpatient setting with continuous vital-sign monitoring. Psychotomimetic and adverse events were recorded repeatedly, with the primary efficacy measure being change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) score. If the patients showed a 50% or higher reduction in MADRS scores on day 2, they received five additional infusions on an outpatient basis (days 3, 5, 8, 10, and 12). Follow-up visits were conducted twice weekly for four weeks, or until relapse.

The results showed that the response criterion was met by nine patients after the first infusion, and again after the sixth infusion, with the mean reduction in MADRS scores after the sixth infusion being 85%. Postketamine, eight of nine patients relapsed, on average, 19 days after the last infusion, with one patient remaining antidepressant-free with minimal depressive symptoms for over 3 months. The ketamine elicited minimal positive psychotic symptoms, with three patients experiencing significant but transient dissociative symptoms. The side effects during and after each ketamine infusion were generally mild. The study was published in the January 15, 2010, issue of Biological Psychiatry.

"These pilot findings suggest feasibility of repeated-dose intravenous ketamine for the acute treatment of treatment-resistant depression,” concluded lead author Marije aan het Rota, Ph.D., of the University of Groningen, and colleagues.

Ketamine is classified as an N-methyl d-aspartate (NMDA) receptor antagonist. At anesthetic level doses, ketamine has also been found to bind to opioid μ receptors and σ receptors. Like other drugs of this class, such phencyclidine (PCP, or "angel dust”), it induces a state referred to as "dissociative anesthesia,” often used as a recreational drug. Ketamine has a wide range of effects in humans, including analgesia, anesthesia, elevated blood pressure, and bronchodilation. Ketamine is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drug, and is a popular anesthetic in veterinary medicine.


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Mount Sinai School of Medicine
University of Groningen