Research Profile - What works for you? Treating depression without trial and error
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Dr. Gustavo Turecki
As a psychiatrist at Montreal's Douglas Mental Health Institute, Dr. Gustavo Turecki specializes in helping people whose depression is persistent and hard to treat. Often, his patients are so mired in despair that they don't get out of bed, can't work and withdraw from their families.
"These are patients who are handicapped by their depression, unable to function... They have lost contact with everything, and feel very guilty because the illness makes them have distorted thoughts," says Dr. Turecki.
One of the most frustrating aspects of depression is that although antidepressants work well for some people, as many as 50% to 70% of patients get little or no relief from the first or even second drug they try. Often, it takes multiple attempts with different antidepressants to find something that helps.
That's why Dr. Turecki and his team are embarking on a study to find biochemical indicators – called biomarkers – that will help predict which patients will respond to particular antidepressants, or which ones won't likely be helped at all.
Each time someone has to try a new drug, they also have to cope with its side-effects, which may include sexual dysfunction, excessive weight gain, dizziness, nausea, headaches, constipation or diarrhea. Since it can take weeks to determine if a medication is effective, the entire process of trying one drug after another can take months, if not years. Sometimes, suicidal patients die before doctors find a drug that works.
"It's trial and error," says Dr. Turecki. "We need tools that can help us to better decide what treatment to offer patients."
By screening the genes of two groups of 100 patients before and after they are treated with different antidepressants, Dr. Turecki will search for activity at the molecular level – the messenger RNA and microRNA– that indicates a response.
"We basically can gain some insight into what changes with treatment in the activity of the genes, changes with treatment that are correlated with side-effects," he says.
Dr. Turecki's goal is to find the biological basis for tests that are as effective in predicting anti-depressant response as biomarker tests are in predicting if women with breast cancer will respond to certain types of chemotherapy. In cases of breast cancer, biomarker screening tests detect changes in levels of proteins in cells that have been linked to hormonal breast cancer. The screening can help determine whether people will respond to the chemotherapy agent tamoxifen, sparing them from getting a toxic drug if they are not likely to benefit from it.
Eventually, Dr. Turecki hopes his research will lead to a blood test that will help patients with depression find the right drug for them – or at least prevent them from having to take an unnecessary drug, and endure its side-effects, if it is unlikely to help.
“If people knew that antidepressants were not a good option for them, they could consider other treatments, such as psychotherapy, intracranial magnetic stimulation or electroconvulsive therapy,” Dr. Turecki says.
Having a blood test based on biomarkers would "minimize suffering by identifying a more effective treatment right away."
"You can save lives, you save money, and these people can more quickly return to the workforce," says Dr. Turecki.
For people with chronic depression, the use of biomarkers to predict their response to antidepressants is a development Dr. Turecki believes will provide hope. It will enable him to guide patients to the right treatment, so that he sees more patients return to productive lives.
"It's very rewarding as a clinician to see the patients who come (here) very ill, and then do improve and move on with their lives. I really enjoy that," he says.
"It's trial and error. We need tools that can help us to better decide what treatment to offer patients."
- Dr. Gustavo Turecki, Douglas Mental Health Institute
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