A recent study suggests that depressed patients who may be resistant to other forms of therapy may benefit from the administration of ketamine. The fact that ketamine may prove useful in the treatment of depression was first noted by Yale researchers, and the research has continued here. According to researchers at the Yale School of Medicine, there is the possibility that
the pediatric anesthetic helps regenerate synaptic connections between brain cells damaged by stress and depression, according to a review of scientific research written by Yale School of Medicine researchers and published in the Oct. 5 issue of the journal Science.
Ketamine works on an entirely different type of neurotransmitter system than current antidepressants, which can take months to improve symptoms of depression and do not work at all for one out of every three patients. Understanding how ketamine works in the brain could lead to the development of an entirely new class of antidepressants, offering relief for tens of millions of people suffering from chronic depression (Yale University, 2012).
One of the elements of the effects of ketamine on depressed patients that has garnered the most attention from researchers, in other words, is how quickly it tends to alleviate symptoms. The antidepressant effects of ketamine, unfortunately, last only 7-10 days (Yale University, 2012). Furthermore, it seems to help patients who have tried other medications to no avail. Unfortunately, ketamine is notorious for being used as a recreational drug, and is associated with psychotic reactions in larger doses (Yale University, 2012). Historically, it has typically been used by veterinarians as an anaesthetic. One of the idiosyncrasies of ketamine use that has researchers particularly interested is its unique neurochemical mechanism of action as opposed to other conventional antidepressant drugs: "In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. Research at Yale has shown that damage of these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine" (Yale University, 2012).
Despite this unusual neurochemical mechanism of action, some researchers suggest that ketamine, like more conventional antidepressants, does produce its antidepressant effect through the manipulation of serotonin. For example, experiments conducted with PET scanning by researchers in Japan have suggested that ketamine exerts its antidepressant effects through manipulation of the presence of serotonin in the part of the brain associated with the regulation of motivation (RIKEN, 2014).
The team performed PET imaging studies on four rhesus monkeys with two tracer molecules related to serotonin (5-HT) that bind highly selectively to the serotonin 1B receptor 5-HT1B and the serotonin transporter SERT.
From the analysis of the 3 dimensional images generated by the PET scans, the researchers could infer that ketamine induces an increase in the binding of serotonin to its receptor 5-HT1B in the nucleus accumbens and the ventral pallidum, but a decrease in binding to its transporter SERT in these brain regions. The nucleus accumbens and the ventral pallidum are brain regions associated with motivation and both have been shown to be involved in depression.
In addition, the researchers demonstrate that treatment with NBQX, a drug known to block the anti-depressive effect of ketamine in rodents by selectively blocking the glutamate AMPA receptor, cancels the action of ketamine on 5-HT1B but not on SERT binding.
Taken together, these findings indicate that ketamine may act as an antidepressant by increasing the expression of postsynaptic 5-HT1B receptors, and that this process is mediated by the glutamate AMPA receptor(RIKEN, 2014)
Yale University. (2012, October 4). How ketamine defeats chronic depression. ScienceDaily. Retrieved May 31, 2014 from www.sciencedaily.com/releases/2012/10/121004141747.htm
RIKEN. (2014, January 7). Ketamine acts as antidepressant by boosting serotonin. ScienceDaily. Retrieved May 31, 2014 from www.sciencedaily.com/releases/2014/01/140107102442.htm