Weekly infusions of ketamine have the benefits of initial and repeated depression

Jennifer L. Phillips, PhD

A new study shows that weekly infusions of ketamine are badociated with a steady and sustained reduction in depressive symptoms in patients with treatment-resistant depression.

The results, considered new among studies evaluating the administration of ketamine in patients with treatment-refractory depression, show the promising role that the controversial drug could play in psychiatric care.

A team of investigators, led by Jennifer L. Phillips, PhD, a scientist badociated with the Mood Disorders Research Unit at the Royal Mental Health Research Institute, cross-matched double blind, randomized study of the single infusion of ketamine and controlled active midazolam. The evaluation, conducted among 41 participants with treatment-resistant depression in a single treatment center, treated six open-label ketamine infusions, three times a week, in two patients with a relapse of depressive symptoms.

Patients who reported a decrease of at least 50% in the Montgomery – Åsberg Depression Rating Scale (MADRS) received 4 additional infusions once a week during the course of their stay. a phase of maintenance.

Individuals who received a single infusion of ketamine reported a significant reduction in depressive symptoms at the primary endpoint of 24-hour efficacy after treatment compared to midazolam-treated patients. The therapy showed cumulative antidepressant effects after repeated infusions, as well as a doubled antidepressant response rate in patients, according to mixed linear models.

The investigators found that 59% of the patients met the response criteria following repeated infusions, with 3 infusions serving as the median dosage required to obtain the response. In patients receiving weekly maintenance infusions, no further improvement in MADRS scores has been reported.

The first discoveries of this type occur just one month after the Food and Drug Administration (FDA) approved esketamine nasal spray (Spravato) for the treatment of treatment-resistant depression. At the time, the therapy marked history as the first breakthrough treatment indicated for depression in 30 years – and was one of the first hallucinogenic drugs to indicate the indication of a common condition.

Dennis Charney, MD, Dean of Icahn School of Medicine at Mount Sinai and a member of the Yale University team who led the pioneering trials of antidepressants on ketamine in the 1990s, said MD Magazine® that microdosing or the implementation of controversial treatments for psychiatric care requires what any other trial requires: control, safety and a carefully evaluated efficacy endpoint.

"Whatever treatment is evaluated, you have to follow these scientific approaches," said Charney. "For diseases that do not have effective treatments, you have to be open minded."

Dan Iosifescu, MD, badociate professor of psychiatry at the NYU School of Medicine, director of clinical research at the Nathan S. Kline Psychiatric Research Institute, and prominent ketamine investigator, said MD Mag that, among other reasons, ketamine will never achieve home treatment because of its misuse as a Special-K street drug. He predicted that the marketed treatment would be expensive and that it would be prescribed as a long-term treatment for a small population of patients with depression.

"For the majority of people who benefit from it, they will need essentially time for other treatments, whether it is pharmacotherapies or device-based treatments, or psychotherapies." because they start to work much more slowly than ketamine, "he said. .

Regardless of the uses of this drug on the market, Phillips and colleagues have positively concluded that ketamine has initial and repeated benefits for antidepressant effects as a weekly infusion.

"These results provide new data on effective delivery strategies for ketamine in patients with treatment-resistant depression," they wrote. "Future studies should further develop the optimization of the administration to better translate the use of ketamine into clinical parameters."

The study titled "Simple, repeated and maintenance ketamine infusions for the treatment of treatment-resistant depression: randomized controlled trial" was published online in The American Journal of Psychiatry.