Conquering treatment-resistant depression with ketamine

May 17, 2021

Depression is one of the most prevalent causes of disability in the world. While antidepressants can help alleviate the symptoms of depression, treatment-resistant depression is very common and its impact on the lives of those that have it can be devastating. Dr. Roger McIntyre is studying whether the drug ketamine can alleviate treatment-resistant depression quickly and effectively. He believes it has the potential to revolutionize how we treat depression and transform the lives of millions.





What is Treatment-resistant depression?

RM: Treatment-resistant depression is defined as the presence of ongoing symptoms of depression or functional problems because of depression despite treatment with at least two antidepressants. Unfortunately, it is common and is reported to occur in about 30% to 60% of people affected by depression.

What motivated this research?

RM: Depression causes significant hardship for people and it's the most common reason people across Canada and the United States are not able to function at their best. Antidepressants have been available since the mid 1950s. Despite this, most people who take antidepressants don't feel as though they have their lives back as they have ongoing symptoms and just can't function day-to-day. Ketamine stands out as a potential alternative to the antidepressants we’ve been using, with the potential to be effect for those with treatment-resistant depression. The United States Food and Drug Administration has described it as a “breakthrough".  Most antidepressants take weeks to be effective, and we were especially interested in determining if ketamine can alleviate symptoms more quickly.

How should the general public and clinicians view ketamine as a treatment option for psychiatric illness?

RM: The general public and clinicians should see ketamine as one of the most important medication advances in treating depression in seven decades. Our research showed that ketamine can improve the symptoms of depression within 1 to 2 days. This is very different from drugs like fluoxetine (commonly know by the brand name Prozac) that often take 4 to 8 weeks to be effective. Also, ketamine is the first drug for depression that's been shown to improve thoughts of suicide within a couple of days, something that's never been reported with conventional antidepressants.

What was the most important finding of this study, in your opinion?

RM: Hope! People who try many antidepressants often lose hope that their depression can be treated. Ketamine provides symptom relief within a few days and reduces suicidality. Along with improving functioning, what's been especially interesting and hopeful is that ketamine improves people's general sense of wellbeing.

How does this change treatment in the future?

RM: People who live with depression may soon have access to treatments that can alleviate their symptoms within a few days and allow them to feel like themselves shortly thereafter. It's thrilling to think about the possibility of combining ketamine treatment with counseling and psychotherapy to further increase its benefits and sustain them over the long term.

Any next steps?

RM: We will continue to conduct research to determine whether we can prolong the effects of ketamine so that people will be able to only take it a few times per year. We will continue researching ways to prolong the effects of ketamine and decrease the frequency of doses. It may be possible for people to take ketamine as little as a few times a year. We’ll also explore the possibility of combining it with counseling and psychotherapy to see if we can improve people's wellbeing, their ability to function at work, and their sense of purpose in life.

What is the major take home message for the public?​

RM: Psychiatry is entering the most innovative time for the treatment of depression in seven decades ushered in by the new, rapid-acting antidepressant treatments. It is my view that along with alleviating suffering, our duty as clinicians is to provide hope to people affected by depression. The introduction and development of so-called rapid-acting treatments for depression address both of these imperatives.

ImPACT Committee includes Krista Lanctôt, Alastair Flint, Meng-Chuan Lai and Simone Vigod.

Lipsitz O, McIntyre RS, Rodrigues NB, Kaster TS, Cha DS, Brietzke E, Gill H, Nasri F, Lin K, Subramaniapillai M, Kratiuk K, Teopiz K, Lui LMW, Lee Y, Ho R, Shekotikhina M, Mansur RB, Rosenblat JD. Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110126. doi: 10.1016/j.pnpbp.2020.110126. Epub 2020 Oct 5.