A new study shows that weekly ketamine infusions are associated with continued and maintained reductions in depressive symptoms among patients with treatment-resistant depression. The findings, which are considered novel among studies assessing ketamine administration for patients with treatment-resistant depression; evidence the promising role the controversial drug could play in psychiatric care.

Controversial drug

A team of investigators, led by Jennifer L. Phillips, PhD, an associate scientist in the Mood Disorders Research Unit at The Royal’s Institute of Mental Health Research, conducted a randomized; double-blind crossover comparison of single ketamine infusion versus active placebo control midazolam.  Therefore The assessment; held with 41 participants with treatment-resistant depression at single treatment center; observed patients receive 6 open-label ketamine infusions 3 times per week over 2 once patients had a relapse of depressive symptoms.

Patients who reported a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale (MADRS) received another 4 additional infusions once weekly in a maintenance phase. Those administered a single ketamine infusion reported significantly reduced depressive symptoms at the primary efficacy endpoint of 24 hours post-care versus those treated with midazolam.

Antidepressant response

The therapy showed cumulative antidepressant effects over repeated infusions; as well a doubling of antidepressant response rate in patients; according to linear mixed models. Investigators found that 59% of patients met the response criteria following repeated infusions; with 3 infusions serving as the median dosage required to reach achieved response. In patients receiving weekly maintenance infusions, no further improvement in MADRS scores were reported.

The first-of-its-kind findings come just 1 month following the US Food and Drug Administration (FDA); therefore approval of esketamine nasal spray (Spravato); therefore  for the treatment of patients with treatment-resistant depression. Because At the time; the therapy made history as the first novel treatment indicated for depression in 30 years and headlines as one of the first hallucinogenic drugs to reach indication for a common condition.
Dennis Charney, MD, Dean of Icahn School of Medicine at Mount Sinai and a member of the Yale University team that led pioneering antidepressant ketamine trials in the 1990s; told MD Magazine® that micro dosing or implementing controversial therapies for psychiatric care require what any other trial requires: control, safety, and a carefully-assessed standard for efficacy.

Prominent ketamine investigator

“No matter what treatment is being assess, you have to follow those scientific approaches;” Charney said. “For conditions that don’t have effective treatments available; there should be an open mind.” Adversely; Dan Iosifescu, MD, associate professor of Psychiatry at NYU School of Medicine; director of Clinical Research at Nathan S.
Kline Institute for Psychiatric Research, and prominent ketamine investigator; told MD Mag that among other reasons ketamine will never reach at-home therapy use due to its prominent abuse as street drug Special-K. Because He anticipated the marketed therapy will be costly; and prescribed as long-term therapy for only a small depression patient population.