1. Potera, Carol

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Many of the newest antidepressant drugs are notoriously slow in altering mood, taking several weeks or even months to relieve symptoms. A new study shows that a single intravenous dose of the anesthesia drug ketamine brings relief from depression within two hours.


Researchers at the National Institute of Mental Health treated 12 women and six men (who had had major depression for more than 30 years on average) with either a single infusion of ketamine (0.5 mg/kg) or a saline placebo. A week later, the participants received the opposite treatment. The volunteers, whose average age was 46 years, had failed to respond to previous treatments for major depression. Among those receiving ketamine, half improved within 110 minutes, 71% improved by the end of the first day, and about a third continued to feel benefits after a week. Those in the placebo group showed no improvement in depressive symptoms at any time.


Clinical response was defined as a 50% or greater decline in scores on the Hamilton Depression Rating Scale, which was given to the patients an hour before the infusion and at 40, 80, 110, and 230 minutes, as well as one, two, three, and seven days afterward. Within two hours, ketamine briefly caused people to feel euphoric or disconnected, two well-known adverse effects of the drug. Ketamine significantly relieved symptoms related to depressed mood, with the earliest improvement seen in 40 minutes.


"To our knowledge, there has never been a report of any other drug or somatic treatment [horizontal ellipsis] that results in such a dramatic rapid and prolonged response with a single administration," conclude the study authors. Moreover, they call the prolonged week-long response of ketamine "remarkable," considering the drug's half-life of about two hours.


Unlike existing drugs for depression that target the neurotransmitters dopamine and serotonin, ketamine blocks the brain receptor N-methyl-D-aspartate (NMDA), which receives signals from a different neurotransmitter called glutamate. These results give a new direction for researchers to pursue in their search for better therapies. Ketamine could be redesigned to be safer, or pharmaceutical researchers could search for new compounds that target NMDA or glutamate.


Carol Potera


Zarate CA, et al. Arch Gen Psychiatry 2006; 63(8):856-64.



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