Cognitive Function Rapidly Restored After Ketamine Treatment, Decreases Suicidality

While it hasn't yet been approved by the FDA, ketamine is considered a paradigm shift for depression research and treatment as the first fast-acting antidepressant to effectively treat symptoms of treatment-resistant mood disorders.

Usually used alone for pain control or with other anesthetic medicine during surgery, ketamine's potential to to treat severe depression is a hot topic of research. A new study from Columbia University presents new findings to reduce depressive symptoms and thoughts of suicide within just 24 hours.

The Research

Researchers conducted neuropsychological testing on 78 individuals with depression and clinically significant suicidal ideation before treatment and one day after. Half of the participants were treated with intravenous ketamine and half with the sedative midazolam, which is used to treat anxiety and depression.

The findings, published in the Journal of Clinical Psychiatry, show that one dose of ketamine rapidly improved the thinking and reasoning of individuals with suicidal ideations to make them feel safer and less likely to harm themselves. Many of these individuals hadn't responded to other antidepressants previously.

While the exact mechanism is still unclear, the improvement in distorted thinking gives researchers a better understanding of how ketamine affects the brain. Some proposed biomedical mechanisms include down-regulation of neurological pathways commonly associated with rumination, a characteristic of suicidal thoughts.

"We found that suicidal ideation is not just related simply to severity of depression," said senior author J. John Mann, MD, in a release. "There are other reasons, including cognitive improvements that are related to a decline in suicidal ideation and thereby make those who are suicidal safer."

For the participants that responded positively to ketamine, the results continued for up to six weeks after the initial infusion alongside antidepressants. However, long-term effects of continued ketamine use are unknown, so further research is still necessary.

Ketamine and Mental Health

Psychotherapist Ben Medrano, MD, serves as medical director of Field Trip Heath New York, where psychotherapy is paired with psychedelic medicine. Ketamine is a regular part of treatment for individuals struggling with depression and anxiety.

"We have found ketamine-assisted psychotherapy to be one of many helpful tools to springboard people to a state of greater agency to snap out of it and re-enter a flexible state where self care begins to feel more possible," Medrano says.

Just as research has produced promising findings around ketamine for treating depressive symptoms, Medrano says he regularly sees the same encouraging results in practice. The introduction of ketamine allows patients to access the root cause of their issues and work toward addressing them.

"We've observed that the pairing of ketamine with psychedelic modalities may offer the opportunity to access the unconscious and explore underlying issues that may contribute to depression and anxiety," Medrano says. "Meaning-making, be it spiritual or philosophical, has also been a key factor in the healing process of (ketamine-assisted psychotherapy)."

Although this evidence is promising and the FDA has approved a derivative of ketamine, Esketamine nasal spray, as an effective treatment for treatment-resistant depression in conjunction with oral antidepressants, some patients and professionals are still hesitant to explore ketamine's potential.

Medrano notes that recreational use of ketamine and its association with animal tranquilizers have lead to major dismissal of its validity as a treatment. At the same time, some academics don't categorize ketamine as a psychedelic, and while it certainly doesn't produce the same effects as LSD or psilocybin, Medrano says, the limiting qualification of "dissociative anesthetic" ignores any mystical states that can be achieved through ketamine-assisted therapy.

"Taking into account such misunderstandings, it's important to acknowledge their influence on the mindset of a KAP participant," Medrano says. "Psychedelics have the potential to amplify pre-existing beliefs, accurate or not. Therefore, reductive or false perspectives like these may detract from positive outcomes."