Health and Psychology

According to the National Institute for Mental Health, antidepressant medications or cognitive behavioral therapy generally require six to eight weeks to have an effect. That's due to how long it takes to increase seratonin in the brain.  In the past five years, ketamine and scopolamine have been shown to reduce depression experimentally, including thoughts of suicide, within six hours.

This past year saw the first identification of biological indicators of how the brain responds to ketamine and the first demonstration of the molecular mechanism for this rapid response—the rapid activation of an enzyme, mTOR, which regulates cell growth, proliferation, and survival.  In addition, new targets for intervention have emerged, including MKP-1, a protein involved in the resiliency of brain cells to stress.

While several pharmaceutical companies moved away from psychiatric medication development this year, the scientific opportunities for new targets and new approaches have never been better.

About ten years ago, scientists at Connecticut Mental Health Center found that in lower doses, ketamine, normally used as a general anasthetic for children, appeared to relieve patients with depression. Since then, other studies have shown that over two thirds of patients who don't respond to all other types of anti-depressants improved hours after receiving ketamine, said Duman.

The problem with using ketamine more widely to treat depression has been the fact it has to be given intravenously under medical supervision, and it can also cause short-term psychotic symptoms.  So Duman and colleagues decided to investigate the effect of ketamine on the brain to see if it might reveal suitable targets for other safer and easier to adminster drugs.

" ... the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified," they wrote.

They found that ketamine acts on a pathway that controls the formation of new synaptic links between neurons, encouraging synaptogenesis; they wrote that they observed:

" ... increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats."

This discovery not only brings new hope to the 40 per cent or so of patients with depression who don't respond to medication, but to many others who only experience relief after months and sometimes years of treatment. 

The researchers also noted that ketamine has already shown to be effective as a rapid way to treat people with suicidal thoughts, many such patients usually only respond weeks later with traditional drugs or respond to electroconvulsant shock therapy.