The Effect of Ketamine on Optimism
Post by Megan McCullough
The takeaway
Individuals with treatment-resistant depression that were given doses of ketamine exhibited more optimism over the course of treatment. This suggests that ketamine’s antidepressant effects may in part be a result of the positive cognitive effects of ketamine.
What's the science?
Ketamine, an anesthetic that blocks NMDA receptors, is currently being investigated as a therapy for treatment-resistant depression (TRD). Although previous randomized clinical trials have shown ketamine to have an antidepressant effect, there is a gap in research concerning the cognitive effects of ketamine and its role in treating TRD. One marker of TRD is the lack of optimism bias, the tendency in healthy individuals to update personal beliefs following good news more than updating beliefs after bad news. This week in JAMA Psychiatry, Bottemanne and colleagues investigated the role of ketamine in restoring optimism bias in individuals with TRD.
How did they do it?
Participants included 30 healthy control individuals and 26 patients with TRD. Participants with TRD were given three doses of ketamine intravenously over the course of a week. Healthy participants received no doses. Participants in the treatment group were assessed throughout the study for depressive symptoms using an established depression rating scale. All participants completed a belief-updating task to measure optimism bias. This task asked participants to estimate their likelihood of experiencing different adverse life events before and after finding out the actual likelihood of these events happening in the general population. Those with TRD would tend to have a more negative outlook on the course of their own compared to healthy individuals. This paradigm was used as a measure of the efficacy of ketamine treatment in the participants with TRD. Statistical tests, including linear mixed-effects models, were then run to examine the effects of ketamine on belief updating.
What did they find?
Overall, the authors found that ketamine decreased depressive symptoms in individuals with TRD. Participants who received ketamine treatments showed an increase in optimism about their personal lives as soon as four hours after their first ketamine dose. This increase in optimism was correlated with a reduction in scores on the depression evaluation. These results suggest that ketamine has cognitive effects that are associated with the alleviation of major depression symptoms such as negative outlook and lack of an optimism bias.
What's the impact?
This study is the first to show that individuals with TRD showed an increase in optimism bias and a decrease in depressive symptoms over the course of a week of ketamine treatments. The data in this study suggest that ketamine has immediate cognitive effects that alleviate symptoms in those with depression.