Harvard Mental Health Letter

Research suggests new drug targets for depression

Pilot studies of ketamine intrigue scientists, but risks of this anesthetic limit its clinical use.

Two small government-funded randomized controlled trials — one conducted in patients with treatment-resistant major depression and the other in those with treatment-resistant bipolar depression — have found that a single infusion of the anesthetic ketamine rapidly and significantly restored mood, energy, and interests. Although intriguing, at this point the results are more useful to researchers than to clinicians. Even at low doses, ketamine has significant side effects. Abused at higher doses, the drug is known on the streets as "Special K."

Ultimately, the ketamine studies may prove more interesting for helping researchers probe for new antidepressant drug targets. Most of the widely prescribed antidepressants affect neurotransmitter systems involving serotonin, which have long been implicated in mood disorders. Ketamine acts on a different neurotransmitter system, suggesting an alternative way to explore the neurobiology of depression.

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