David Baxter PhD
Late Founder
Ottawa doctor explores use of well-known anesthetic to treat patients with serious depression
By Pauline Tam, Ottawa Citizen
August 19, 2012
On a recent Thursday, one of Dr. Pierre Blier?s patients came to his clinic for an emergency appointment. The 44-year-old woman was so depressed that she was contemplating suicide.
?We can?t let her go home,? the clinician who assessed her told Blier. ?She?s going to kill herself. She has a plan. She knows when she?s going to be alone.?
Blier, a physician researcher at the Royal Ottawa Mental Health Centre, had followed the woman long enough to know that her feelings of despair were particularly difficult to treat, even when she took antidepressants in complex combinations. To defuse the latest crisis, drastic measures would be needed.
Blier offered his patient a choice. She could receive electroconvulsive, or shock, therapy, which uses a brief electrical jolt to induce a brain seizure that, in some patients, can provide rapid, short-term relief from severe depression.
Or she could try an experimental injection of ketamine, a 50-year-old drug commonly used as an anesthetic for humans and animals ? and abused as the club drug known as Special K.
When other medications fail, small doses of ketamine have been shown to deliver almost instant relief in patients with treatment-resistant depression or bipolar disorder.
The downside is the drug?s mood-lifting effects last no more than a few days. Scientists are also unsure whether repeated use of ketamine, alongside antidepressants, would produce lasting effects. The long-term impact on brain function and the risk of abuse are also unknown.
Indeed, because of ketamine?s checkered history, Health Canada has declared it a narcotic and restricted the way it?s dispensed. The drug often induces hallucinations, like whispering voices or light trails, with frequent users reporting out-of-body experiences.
Despite the risks, Blier?s patient opted for the ketamine treatment, making her an early case study in his ongoing tests of the drug?s potential to ease some of the most troublesome cases of depression.
Because ketamine is already approved as an anesthetic, physicians can use it off label for other purposes. However, the drug is not approved as a treatment for depression. To date, only one study of ketamine?s safety and effectiveness has been conducted in patients, meaning the drug should not be used for depression outside of carefully controlled research settings.
The 2010 study, done by the National Institute of Mental Health in the U.S., was the first to demonstrate ketamine?s promise as a fast-acting, if temporary antidepressant. Although the study was small, with just 18 patients, it was conducted under the highest standards, meaning the trial was randomized, placebo-controlled and double-blinded.
Through a larger study that aims to enrol up to 63 volunteers, Blier wants to learn more about how repeated doses of ketamine act to reduce depressive symptoms, especially in patients who are suicidal. He also wants to understand how the drug interacts with other antidepressants.
So far, scientists have determined that ketamine works by limiting the action of one type of brain receptor that moves nerve signals between neurons, making them work better. Specifically, the drug ?may be hitting the part of the brain where suicide ideation begins,? said Blier, who?s also Canada Research Chair in psychopharmacology.
In his patient, a single ketamine dose initially left her feeling numb and woozy. Within an hour, however, tests showed she had significantly lower levels of despair and anxiety.
?Sixty minutes later, she had a big smile,? Blier said. ?What we saw was that her depression scores had dropped completely and the suicide ideation went down rapidly. In fact, that was where the effect was the most robust.?
While there were no serious side effects, the antidepressant effects of the ketamine faded after 36 hours. Repeated doses over six weeks still left the woman with depressive symptoms, although she told Blier she was able to do some chores around the house instead of being bedridden and crying constantly.
Blier said he started using ketamine last year as a temporary therapy to help the most difficult-to-treat patients manage their suicidal thoughts as they transitioned from medications that had failed to new ones.
That?s because the current crop of antidepressants can take weeks to start working, leaving many patients vulnerable to harming themselves during that lag time.
What?s more, as many as a third of depression sufferers find no relief from any of the existing drugs. Another third tend to experience only a slight improvement, raising the risk of a relapse and long-term atrophy of certain brain regions.
Such limitations highlight the shortcomings in a field where doctors can?t predict who will respond to which drug and at what dosages.
Figuring out the correct combinations ? and why they work ? has been Blier?s focus since the late 1970s, when he started researching ways to make antidepressants work faster and more effectively.
His work has made him a fierce advocate of aggressive strategies to treat depression.
Through meticulously designed drug studies, Blier has shown that the recovery rate in people with the disorder can be doubled by using carefully calibrated combinations of antidepressants right from the start of treatment, rather than as a last resort, which remains the common practice.
Blier, 55, said he was drawn to the field as an undergraduate at Quebec?s Bishop?s University, where he took a course that showed him how some medications could alter human behaviour.
He also had a personal connection to depression. During his university years, he witnessed his father?s own struggle with the illness, and how the medical establishment?s limited knowledge of antidepressants hampered his recovery.
?I saw how devastating depression was,? Blier said. ?He stayed in his room all the time, sleeping. When he would get up, he was very irritable. My mother had her own business so we didn?t suffer financially. But the atmosphere in the house was really not pleasant.?
Since that time, Blier?s fascination with antidepressants has taken him from his hometown of Montreal to Paris, back to Montreal and then Florida.
In 2004, he was recruited to the University of Ottawa?s Institute of Mental Health Research and to the Royal, where he holds the first endowed chair in mood disorders research.
His seven-year, $1.4-million federal grant through the Canada Research Chairs program was recently renewed for a second term, meaning Blier will continue to use his research and clinical practice to give Ottawa-area patients first crack at his experimental therapies.
By Pauline Tam, Ottawa Citizen
August 19, 2012
On a recent Thursday, one of Dr. Pierre Blier?s patients came to his clinic for an emergency appointment. The 44-year-old woman was so depressed that she was contemplating suicide.
?We can?t let her go home,? the clinician who assessed her told Blier. ?She?s going to kill herself. She has a plan. She knows when she?s going to be alone.?
Blier, a physician researcher at the Royal Ottawa Mental Health Centre, had followed the woman long enough to know that her feelings of despair were particularly difficult to treat, even when she took antidepressants in complex combinations. To defuse the latest crisis, drastic measures would be needed.
Blier offered his patient a choice. She could receive electroconvulsive, or shock, therapy, which uses a brief electrical jolt to induce a brain seizure that, in some patients, can provide rapid, short-term relief from severe depression.
Or she could try an experimental injection of ketamine, a 50-year-old drug commonly used as an anesthetic for humans and animals ? and abused as the club drug known as Special K.
When other medications fail, small doses of ketamine have been shown to deliver almost instant relief in patients with treatment-resistant depression or bipolar disorder.
The downside is the drug?s mood-lifting effects last no more than a few days. Scientists are also unsure whether repeated use of ketamine, alongside antidepressants, would produce lasting effects. The long-term impact on brain function and the risk of abuse are also unknown.
Indeed, because of ketamine?s checkered history, Health Canada has declared it a narcotic and restricted the way it?s dispensed. The drug often induces hallucinations, like whispering voices or light trails, with frequent users reporting out-of-body experiences.
Despite the risks, Blier?s patient opted for the ketamine treatment, making her an early case study in his ongoing tests of the drug?s potential to ease some of the most troublesome cases of depression.
Because ketamine is already approved as an anesthetic, physicians can use it off label for other purposes. However, the drug is not approved as a treatment for depression. To date, only one study of ketamine?s safety and effectiveness has been conducted in patients, meaning the drug should not be used for depression outside of carefully controlled research settings.
The 2010 study, done by the National Institute of Mental Health in the U.S., was the first to demonstrate ketamine?s promise as a fast-acting, if temporary antidepressant. Although the study was small, with just 18 patients, it was conducted under the highest standards, meaning the trial was randomized, placebo-controlled and double-blinded.
Through a larger study that aims to enrol up to 63 volunteers, Blier wants to learn more about how repeated doses of ketamine act to reduce depressive symptoms, especially in patients who are suicidal. He also wants to understand how the drug interacts with other antidepressants.
So far, scientists have determined that ketamine works by limiting the action of one type of brain receptor that moves nerve signals between neurons, making them work better. Specifically, the drug ?may be hitting the part of the brain where suicide ideation begins,? said Blier, who?s also Canada Research Chair in psychopharmacology.
In his patient, a single ketamine dose initially left her feeling numb and woozy. Within an hour, however, tests showed she had significantly lower levels of despair and anxiety.
?Sixty minutes later, she had a big smile,? Blier said. ?What we saw was that her depression scores had dropped completely and the suicide ideation went down rapidly. In fact, that was where the effect was the most robust.?
While there were no serious side effects, the antidepressant effects of the ketamine faded after 36 hours. Repeated doses over six weeks still left the woman with depressive symptoms, although she told Blier she was able to do some chores around the house instead of being bedridden and crying constantly.
Blier said he started using ketamine last year as a temporary therapy to help the most difficult-to-treat patients manage their suicidal thoughts as they transitioned from medications that had failed to new ones.
That?s because the current crop of antidepressants can take weeks to start working, leaving many patients vulnerable to harming themselves during that lag time.
What?s more, as many as a third of depression sufferers find no relief from any of the existing drugs. Another third tend to experience only a slight improvement, raising the risk of a relapse and long-term atrophy of certain brain regions.
Such limitations highlight the shortcomings in a field where doctors can?t predict who will respond to which drug and at what dosages.
Figuring out the correct combinations ? and why they work ? has been Blier?s focus since the late 1970s, when he started researching ways to make antidepressants work faster and more effectively.
His work has made him a fierce advocate of aggressive strategies to treat depression.
Through meticulously designed drug studies, Blier has shown that the recovery rate in people with the disorder can be doubled by using carefully calibrated combinations of antidepressants right from the start of treatment, rather than as a last resort, which remains the common practice.
Blier, 55, said he was drawn to the field as an undergraduate at Quebec?s Bishop?s University, where he took a course that showed him how some medications could alter human behaviour.
He also had a personal connection to depression. During his university years, he witnessed his father?s own struggle with the illness, and how the medical establishment?s limited knowledge of antidepressants hampered his recovery.
?I saw how devastating depression was,? Blier said. ?He stayed in his room all the time, sleeping. When he would get up, he was very irritable. My mother had her own business so we didn?t suffer financially. But the atmosphere in the house was really not pleasant.?
Since that time, Blier?s fascination with antidepressants has taken him from his hometown of Montreal to Paris, back to Montreal and then Florida.
In 2004, he was recruited to the University of Ottawa?s Institute of Mental Health Research and to the Royal, where he holds the first endowed chair in mood disorders research.
His seven-year, $1.4-million federal grant through the Canada Research Chairs program was recently renewed for a second term, meaning Blier will continue to use his research and clinical practice to give Ottawa-area patients first crack at his experimental therapies.
