While depression has been around for hundreds, if not thousands, of years, it was not until the 1950s that pharmacologic agents began to emerge to help treat this disorder. To date, the drugs prescribed to treat depression operate by increasing the levels of certain neurotransmitters (chemicals in the brain) ??? most notably serotonin and norephinephrine.

Though many patients improve with therapy, there is a subset of patients that do not improve when administered commonly used antidepressant medications. In fact, in patients that respond (positively) to antidepressants, there is often delays of weeks to months before the benefit of these medications are realized. A research study that was published in the premier science journal, Science (August 20, 2010; Vol. 329, Issue 5994), describes the mechanism whereby ketamine may provide a different, faster, way to treat depression.

The approach taken by the researchers from Yale University was to focus on the glutamate neurotransmitter system. Glutamate is aneurotransmitter that is involved in facilitating a gradual reorganization of neural connections (synapses) and communication between the cells of the brain, called neurons. Ketamine, a drug more typically thought of as an anesthetic, blocks a particular glutamate receptor, called the NMDA receptor.

Interestingly, previous research demonstrated that a single sub-anesthetic dose of ketamine resulted in a rapid antidepressant effect within hours of administration. What???s more, this antidepressant effect could be sustained for up to one week. The mechanism for this action had not been determined prior to the current study, which revealed that ketamine rapidly activates the mammalian target of therapamycin (mTOR) pathway. Activation of the mTOR pathway was shown to increase synaptic signaling proteins and increase the number of new spine synapses in rats. Blockade of this pathway resulted in a blockade of the effects evoked by ketamine resulting in no synaptogensis.

This research may thus shed light as to how ketamine may act as a fast antidepressant.