“If you or I walk into any GP’s office with asthma,” says Dr. Pierre Blier, an Ottawa research physician, “we’re going to come out with at least two medications: a puffer to dilate the bronchial tree, and a steroid to prevent inflammation.”

Dr. Blier is commenting on a strategy familiar to anyone who’s been treated for a major physical illness: prescribing a combination of medications that fight the problem on different fronts.
“And don’t try to tell me,” he continues with some frustration, “that depression isn’t as serious as asthma.”

His impatience comes from a lingering reluctance among physicians to apply the dual-medication strategy to patients who are suffering from a debilitating mental illness that will strike almost three million Canadians at least once in their lives. The good news is that attitudes among doctors are improving; when Dr. Blier first began investigating dual-antidepressant therapies ten years ago, all he encountered was skepticism. “People were throwing stones at me,” he remembers. “‘Blier’s giving two drugs at the same time, maybe giving one for nothing.’ But now people are joining my camp.”

The reason is meticulous research,
combined with clinical practice. In the
mornings, Dr. Blier sees his patients in a sunny corner of his office at the Ottawa Mental Health Centre. But when the morning’s appointments are over, he pulls on a lab coat and takes a short walk up a flight of stairs to a state-of-the-art lab for the study of brain function, funded in part by the Ontario Innovation Trust.

The two spaces are very different—but inextricably connected. What Dr. Blier learns upstairs shapes his practice downstairs—and vice versa. In the medical community, this is known as “translational” research—an iterative process that involves turning the insights of the lab into actual therapies, and insights from therapy into further directions for experimentation. It’s a dialogue, and as in any good conversation, ideas pass both ways.



In the lab, Dr. Blier is seeking to build a better understanding of depression on two fronts. On the one hand, he’s attempting to more accurately isolate the circuits in the brain responsible for depression. What kinds of neurons are malfunctioning, and in what ways? The aim is to provide a more detailed map of “targets” against which antidepressants can be deployed. The other major focus of his research is to describe more accurately the “mechanisms of action” of a variety of antidepressant medications. Exactly how do various drugs act on systems in the brain to counteract the symptoms of depression?

Armed with these findings, Dr. Blier has developed therapies that involve various combinations of two antidepressants, each addressing different targets and operating in different but complementary ways. The two drugs can also be chosen to cancel out each other’s negative side effects.

Patients have responded remarkably—including those whose depression has stubbornly resisted conventional treatment. In studies conducted over the past ten years, Dr. Blier has established that the dual-medication approach increases remission rates in the first six weeks from 25 percent to a remarkable 50 to 60 per cent. “We get sent patients who have failed to see results with three, four, five antidepressants—one after the other. And when they get well, it’s so rewarding.

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