Horse tranquiliser could hold key to antidepressant

By IAN JOHNSTON Time of article published May 6, 2016

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London - A substance produced after taking the drug ketamine could be used to create a fast-acting antidepressant without its harmful side-effects, according to scientists.

Ketamine, which was banned in the UK in 2006 and made a class B drug in 2014, was initially used as a horse tranquiliser by vets but has latterly become better known for its use by clubbers and to facilitate date-rape.

Clinical trials of ketamine in humans have shown it can relieve depression much faster than commonly prescribed drugs, but the problem was it also created the dissociative, euphoric and addictive properties that made it an illegal drug.

So researchers decided to find out what exactly was going on when someone took the drug.

They have now found that it is not ketamine itself but a chemical produced when the body breaks it down that helps relieve depression - in a study in mice.

One of the authors of a paper about the research, Dr Carlos Zarate, said in the journal Nature: “This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works and holds promise for development of more robust and safer treatments.

“Researchers were able to reverse-engineer ketamine''s workings from the clinic to the lab to pinpoint what makes it so unique.”

Another of the researchers, Dr Todd Gould, of Maryland University's School of Medicine, added they now planned to make sure the same process was happening in humans to see if they could isolate the beneficial effects and eliminate the harmful ones.

“Now that we know that ketamine''s antidepressant actions in mice are due to a metabolite, not ketamine itself, the next steps are to confirm that it works similarly in humans, and determine if it can lead to improved therapeutics for patients,” he said.

Dr James Stone, a clinical senior lecture at King's College London's Institute of Psychiatry Psychology and Neuroscience, said the research raised the “exciting” prospect of using the chemical as an antidepressant.

“This paper predicts that it would have a similar very rapid onset of action and efficacy against treatment-resistant depression to ketamine, but that it would lack some of the undesirable side effects such as perceptual distortion and addiction potential,” he said.

However Dr Stone added: “Although these findings are very promising, clinical trials in patients with depression are required.”

Professor Celia Morgan, of Exeter University's psychology department, said abuse of the drug was a “concern for clinicians thinking of using repeated doses of ketamine in the treatment of depression”.

But the paper was a “fascinating advance in understanding how ketamine has these life-changing effects in people with very severe depression”.

“The findings suggest, along with other work, that changes in an area of the brain important in memory called the hippocampus, which allow the brain to more readily form new connections, are important in producing rapid reduction of depression,” she said.

“These findings are in mice, so it still remains to be seen if they translate to humans. We also do not know the exact way in which this metabolite works, rather we know how it doesn't work. So much work needs to be done before we get to the stage of testing such a drug in humans.”

The Independent

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