Ketamine could rapidly treat depression, scientists say

10th November 2012

Depression affects nearly one in five of the US population, causing over $100 billion in economic damage each year. Drug treatments are available, but typically require weeks or months to fully take effect. Now, researchers from Yale have revealed how small doses of ketamine can offer immediate relief from symptoms.

Synaptic links between brain cells are damaged by stress, anxiety and depression. Ketamine helps to regenerate these neural connections, according to a review of the scientific evidence by Yale School of Medicine published in the journal Science.

Ketamine works on a completely different type of neurotransmitter (chemical messenger between neurons) than current antidepressants which can take months to improve symptoms of depression and do not work at all for one in three patients. Understanding how ketamine works in the brain could lead to a new generation of medicine providing immediate relief to millions of people with chronic depression. This could bridge the gap in those critical few days when a suicidal patient may be a threat to themselves or others.

Professor Ronald Duman: "The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century."

Understanding how ketamine works is crucial because of the drug's limitations. Improvements in symptoms, which are evident just hours after ketamine is administered, last only a week to 10 days. In large doses, it can cause dreamlike states, hallucinations and short-term psychosis and is abused as the recreational party drug "Special K."

In their research, Duman and others show how in a series of steps, ketamine triggers release of neurotransmitter glutamate, which in turn stimulates the growth of synapses. Damage of these synaptic connections caused by chronic stress can be rapidly reversed by a single small dose of ketamine.

In the past, efforts to develop drugs replicating the effects of ketamine have produced some promising results, but they do not act quickly enough. Researchers are now investigating alternatives they hope can duplicate the speed and efficacy of ketamine, but without its potential downsides.

Duman: "It's exciting. The hope is that this new information about ketamine is really going to provide a whole array of new targets that can be developed and ultimately provide a much better way of treating depression."

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