Dalhousie professor explores personalized care for depression
Approach promising for those who don’t respond well to traditional drugs
A study led by a Dalhousie University professor and psychiatrist, Dr. Rudolf Uher, has found apotential treatment option for people with depression who don’t respond well to common antidepressants.
The Canadian Biomarker Integration Network in Depression (CAN-BIND) trial included 211 adults in five cities across Canada. The findings of the trial will pave the way for a more personalized treatment approach for depression.
It’s especially important because different people may experience depression in different ways. Some may feel tired and have little energy to do anything, while others may feel agitated.
“Personalized treatment gives people hope in emphasizing that each person’s depression is different and that there’s more approaches to try,” says Uher.
For years, psychiatrists and neuroscientists have been trying to predict what treatments can be useful for different people. So when someone responds poorly to an antidepressant it can be a surprise for the medical practitioner. For the patient, it can be very frustrating, considering the great courage it took for them to seek treatment in the first place.
“They may be very discouraged and reluctant to try another (treatment). And they may feel like they are worse than other people because their depression is not responding well.”
By most existing guidelines, serotonergic antidepressants are the first recommended treatment for depression, according to Uher.
“It’s a combination of easy availability, relatively good efficacy, but also safety.”
Serotonergic antidepressants act by maintaining a balanced level of serotonin in the gap between the nerves in our brain. Serotonin is a small messenger molecule that’s involved in regulating our mood.
Increasing the serotonin levels is associated with good outcomes for people with depression.
The reasons for resistance to serotonergic antidepressants are complex and unclear.
But in 2012, Uher published a study that found depression that is characterized by low interest and reduced activity would have a predicted poor outcome in response to treatment. The findings of this study are replicable.
The advantage of using symptoms to predict whether a treatment could work is the simplicity of the method. A clinical practitioner can identify the interest-activity symptom by asking a list of questions. It doesn’t require laboratory tests, genetic tests or brain imaging.
“But it was very difficult to find alternative treatments that work well for people with predicted poor outcomes.”
This is where the CAN-BIND trial makes progress. The clinical trial found that people who have low interest and reduced activity don’t respond well to the serotonergic antidepressant Escitalopram.
But the trial also found that those people benefit from additional treatment with a partial dopamine agonist (a chemical that activates a biological response when combined with a receptor) called Aripiprazole. Dopamine is another messenger molecule in our brain.
“Dopamine is the surprise molecule. It’s the signal in the brain that signals something unexpected.”
Balanced levels of dopamine help us feel the drive and excitement to do new things. A partial dopamine agonist enhances the effect of dopamine for people with depression who have loss of interest. “So if it works well for them it adds energy. It helps people engage with the world.”
The study comes at a time when people may be vulnerable to depression. According to Statistics Canada, 48 per cent of Canadians reported having very good or excellent mental health between April 24 and May 11, 2020. That’s 20 per cent less compared to results of the 2018 Canadian Community Health Survey.
“COVID-19 has affected so many things that keep people healthy and away from depression,” says Uher. “The schedule of getting outside your home and meeting people and doing something meaningful, that’s being interrupted for so many people.”
He says further investigation is needed into whether the positive effect of Aripiprazole will be replicated using other partial dopamine agonists.
“This is one of the best results I have seen in my career. And yet it’s just a small piece because it concerns just two specific treatments.”
The result is making Uher consider using partial dopamine agonists sooner for patients with severe low interest and reduced activity.
He continues to look for ways to provide personalized treatment for depression, and is now involved in a randomized clinical trial to explore who benefits from psychological therapy as opposed to medication.
“The ability to make it just slightly more likely for people to have a successful experience within a reasonably short time when they make it to see a psychiatrist and combat depression, it can really make a huge difference.”