How old drugs can lead to new treatments for mental illness

Pierre Blier discusses his research into using a well-known anaesthetic to help people with severe depression
By Daniel Kitts - Published on Jul 23, 2018
Pierre Blier is the endowed chair in mood disorders research at the Royal's Institute of Mental Health Research, affiliated with the University of Ottawa.



Did you know that the erectile-dysfunction drug Viagra was originally intended to treat high blood pressure and chest pain? Or that the anti-anxiety medication Valium was developed from chemical compounds meant to create new dyes? The research that has led to many of the world’s best-known drug treatments often started with a very different purpose in mind. And today, researchers are discovering new uses for old medications.

At an Ontario Brain Institute event at 7 p.m. on July 26 at Ottawa’s Canadian Museum of Nature, doctors Pierre Blier and Erick Sell will be discussing how some drugs are being used in new ways to help people with challenging health issues. If you’re unable to attend in person, you can live stream the event on this page at the appointed time. 

In advance of the lecture, spoke with Blier — a professor in the University of Ottawa’s Department of Psychiatry and Cellular/Molecular Medicines — about his research into a new way to treat severe depression.

Tell me about your work with ketamine.

Ketamine is an anaesthetic agent that has been used for 45 years. It’s probably the most widely used anaesthetic agent in the hands of health-care professionals. Using it for a different purpose was first done at Yale for research into schizophrenia. One of the features of schizophrenia is that people can be dissociated from reality. So [the researchers] wanted to mimic a little bit of the psychotic systems in healthy volunteers. And from there, they realized it affected NMDA receptors [in the brain]. And there were indications from animal experiments that this drug actually blocked the NMDA receptors, just like anti-depressants could. In 2011, I started using it at the Royal Ottawa Health Care Group for patients who were severely depressed, for whom anti-depressant medications had not yet worked, or who had severe suicidal ideation.

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When you use ketamine as an anaesthetic, you give a patient a full dose over, say, 10 seconds.  Here, we use a quarter of that dose, and we slowly put it into the patient over 40 minutes.

What effects have you observed?

Half of [the patients] experienced at least a 50 per cent decrease in their symptoms. And more than 80 per cent of them actually had a robust reduction or disappearance of suicidal ideation.

It seems like the body is still a great mystery to us, given that we continue to find new uses for old drugs.

Absolutely. But we know a lot more than we used to. With ketamine, it was not totally a shot in the dark. We knew ketamine could block NMDA receptors, and we knew that NMDA receptors could play a role in the anti-depressant response. So it was, if you want, an educated guess.

In medicine, it’s always a question of risk and benefit. The risks of using ketamine are really minimal, but the benefits are enormous — because we know what the risks of persistent depression are. It’s basically a neurodegenerative disease. If you have chronic depression, you have more chances of developing Alzheimer’s disease prematurely. And of course there’s always the catastrophic outcome of depression, which is suicide.

How close do you think we are to doctors being able to predict what drugs will be most effective for individual patients?

What you’re describing is “a positive predictor of response.” Everybody is searching for that right now. At the Royal and other research sites, we’re going to be looking at electro-convulsive shock treatment versus ketamine. We’re going to do brain imaging, and we’re going to do blood testing — looking for inflammatory mediators for different types of genetic material we can extract from the blood. Hopefully, we’ll come up with a positive predictor of response to prevent what we’re doing now, which is trial and error. We can’t predict who is going to respond to what, so we hope to decrease that guessing time.

This interview has been edited for length and clarity. 

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