For people struggling with severe depression, antidepressants have the potential to provide much-needed relief, but they often take weeks to work. That’s why there is growing excitement about reports that the anesthetic drug ketamine, when delivered intravenously in very low doses, can lift depression and suicidal thoughts within a matter of hours. Still, there has been reluctance to consider ketamine for widespread treatment of depression because, even at low doses, it can produce very distressing side effects, such as dissociation—a sense of disconnection from one’s own thoughts, feelings, and sense of identity. Now, new findings suggest there may be a way to tap into ketamine’s depression-fighting benefits without the side effects.
In a mouse study published in the journal Nature, an NIH-funded research team found that the antidepressant effects of ketamine are produced not by the drug itself, but by one of its metabolites—a substance formed as the body breaks ketamine down. What’s more, the work demonstrates that this beneficial metabolite does not cause the risky dissociation effects associated with ketamine. While further development and subsequent clinical trials are needed, the findings are a promising step toward the development of a new generation of rapid-acting antidepressant drugs.
Caption: Depressed patients with higher activity in the anterior insula (where the green lines intersect) did better with medication than cognitive behavior therapy. Source:Helen Mayberg, Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences
Today, figuring out who will benefit from which antidepressant medication is hit or miss—physicians prescribe a medication to treat major depression for two to three months, and then gauge the results. This trial and error is frustrating and expensive; typically only about 40% get well after this first treatment or see an improvement in symptoms. The other 60% must try a different drug or some other approach. In a new NIH funded study, researchers showed how brain scans could predict which individuals would benefit from a medication and which might respond better to psychotherapy .