Joshua Rosenblat
Ketamine "is a very helpful tool to have in the tool belt," says Dr. Joshua Rosenblat, staff psychiatrist, Mood Disorders Psychopharmacology Unit in UHN’s Centre for Mental Health. (Photo: UHN)

Specializing in treatment-resistant mood disorders means that Dr. Joshua Rosenblat's patients typically come to him having tried more than a dozen types of antidepressant medication – all of them unsuccessful in alleviating their suffering.

But the staff psychiatrist at the Mood Disorders Psychopharmacology Unit (MDPU) in UHN's Centre for Mental Health believes there may be hope for patients with this often debilitating condition.

Ketamine – a fast-acting anaesthetic widely known as a club drug in the 1990s – has been generating enthusiasm across the psychiatric community for its ability to rapidly relieve depression symptoms and suicidal thoughts in some patients.

Dr. Rosenblat first came across the drug's potential as a Resident in 2016 while writing a paper on novel treatments for mood disorders. He's since developed extensive expertise with ketamine and provided it as a treatment option for his patients. More than half of them respond positively – much higher than the 10 per cent to 20 per cent response treatment-resistant patients get with more conventional methods.

And while the drug – and other psychedelic treatments for depression – has generated excitement and media attention, Dr. Rosenblat cautions against overhyping it.

"Ketamine is definitely a game changer, but it's not a cure all," says Dr. Rosenblat. "It's a very helpful tool to have in the tool belt."

It remains relatively under studied at the randomized clinical trial level. Dr. Rosenblat aims to address this knowledge gap in an upcoming study of intravenously administered ketamine for treatment-resistant bipolar depression (TRBP). Participants will receive multiple infusions to determine if repeated doses can sustain and increase antidepressant effects, another rare inclusion in ketamine studies.

'Promise is not enough anymore'

Dr. Rosenblat believes the trial will be the largest ketamine study for TRBP. It will be fully funded by a half-million-dollar grant from the Canadian Institute of Health Research (CIHR), and marks the first time they are funding an IV ketamine study for TRBP. 

"There is so much promise in ketamine, but promise is not enough anymore," says Dr. Rosenblat. “We actually need to do the study to say if this is effective or not."

The trial will be run out of both UHN and Braxia Scientific's Canadian Rapid Treatment Centre of Excellence, a community clinic specializing in ketamine treatments, where Dr. Rosenblat is cross-appointed as Chief Medical and Science Officer.

"Depression therapeutics have been stuck in a cul-de-sac for far too long," says Dr. Roger McIntyre, Medical Director, MDPU, who is a co-principal investigator on the forthcoming study, and a mentor to Dr. Rosenblat since they were paired for a clerkship elective in 2013.

"Joshua has an uncanny ability to implement both original and applied research that will greatly improve in the near term the lives of people affected by depression and bipolar disorder," Dr. McIntyre says.

Besides receiving his first CIHR grant, it's been a busy 12 months for Dr. Rosenblat – he finished an MSc in Pharmacology and Toxicology, was promoted to assistant professor at the University of Toronto, began independently supervising graduate students, and published 40 papers in peer-reviewed journals, all while dividing his time between patients and research.

'So much research to be done'

"The ideas have been catching on where I've been fortunate to get funding and get projects off the ground," Dr. Rosenblat says, crediting his colleagues for spurring him on. “I sometimes joke that MDPU is not a clinic, it's a way of life."

Dr. Rosenblat initially set out to be a cardiologist in medical school, but a fortuitous rotation to Chatham, Ont. placed him in the psychiatry program and he never looked back.

"It seemed like the final frontier," Dr. Rosenblat adds. “We kind of know how the heart works, but as it relates to psychiatry, we still don't have even a basic understanding of how the brain actually works.

"There is so much research to be done that in our lifetime we could actually make tremendous gains."

Depression has many causes and different people need different types of treatment. Dr. Rosenblat sees this exemplified in UHN's Poul Hansen Centre for Depression, which brings together such varied approaches as psychotherapy, pharmacology, and repetitive transcranial magnetic stimulation (rTMS).

"These patients are suffering a lot, just to get through the day," he adds. "It's understandable that they wish there was something that could just flick the switch.

"I think it's helpful to maintain a degree of hope that maybe there is a solution. It pushes us as a field to say, can we actually find a cure?"

Dr. Rosenblat will begin recruiting patients for the ketamine clinical trial later this year with final results expected in 2024.

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