People who suffer from severe depression may benefit from a reduction in suicidal ideation after receiving ketamine treatment, according to a new study in the Journal of Clinical Psychiatry. Fascinatingly, however, the authors suggest that this decrease in suicidality may be driven by enhanced neurocognition rather than by any improvement in depressive symptoms.
The study follows on from earlier work conducted by the same group of researchers at Columbia University, in which depressed patients were treated with either ketamine or another sedative called midazolam. A day later, participants who had received ketamine displayed significantly greater reductions in suicidal ideation than those who had received midazolam, regardless of any changes in their depression scores.
This finding hints toward the possibility that ketamine may treat suicidality via a mechanism that is independent of its anti-depressant properties. Given that improvements in neurocognition have previously been associated with reduced suicidal ideation, the researchers sought to determine if ketamine produces its effects by boosting cognitive functioning.
Returning to the same group of participants that took part in their earlier study, the authors once again supplied half of their patients with ketamine and the other half with midazolam. Twenty-four hours later, they asked their volunteers to complete a series of cognitive tasks, in order to determine whether either drug altered their thinking and reasoning abilities.
After crunching the data, the authors discovered that ketamine was associated with significantly greater improvements in “cognitive control”, a trait that has been linked to suicidal ideation. This attribute was measured using a battery of tests such as the Stroop tasks, in which participants are presented with a color word in an incongruent color – such as the word "green" in red lettering – and must state the color of the font as quickly as possible.
Once again, this change in cognitive performance was completely unrelated to alterations in depressive symptomology, implying that ketamine may help to reduce suicidality via a mechanism that is unrelated to its effects on depression.
“We found that suicidal ideation is not just related simply to severity of depression,” explained senior study author Professor J. John Mann in a statement. “There are other reasons, including cognitive improvements that are related to a decline in suicidal ideation and thereby make those who are suicidal safer.”
A derivative of ketamine, known as esketamine, was approved by the US Food and Drug Administration (FDA) in 2019 for the treatment of severe depression, despite the fact that the drug’s modes of action are not yet fully understood. This latest research sheds valuable new light on the therapeutic potential of this controversial drug, suggesting that it may help to attenuate suicidality by enhancing the thinking and reasoning capacities of depressed patients.