Treatment Resistant Depression found to respond to new version of ketamine AND medication

Treatment Resistant Depression found to respond to new version of ketamine AND medication

 “Novel Intranasal Ketamine Effective for Resistant Depression” was posted online by Medscape on 1-9-18. This article reports on a study that builds on previous research about of ketamine for treatment resistant depression (TRD). Many of the previous studies, however, have suffered from methodological problems, including small-sometimes very small-numbers of subjects and very basic research design. The current study started by screening under 26 adults with MDD and assessed to fit the TRD pattern, with 67 selected for the randomized treatment protocol, and 60 completed the complete, multi-stage research protocol which included two double-blind treatment periods.

The current study started by screening 126 adults with MDD initially assessed to fit the TRD pattern.  67 were subsequentlyselected for the randomized treatment protocol, and 60 completed the complete, multi-stage research protocol which included two double-blind treatment periods.

The study compared intranasal ketamine, delivered in the form of esketamine, alone and in combination with antidepressant medication. Of course, these treatments are also compared to placebo treatments. Three doses of esketamine were studied. The results found the most benefit with combination of esketamine and an oral antidepressant medication, and also found more benefits at higher dose of esketamine. Post-treatment follow-up was conducted for up to eight additional weeks after an initial two-week assessment.

The study reports primary findings: first, significant reduction of depression symptoms was found at one week. Second, improvements in symptoms were sustained up to two months. Third, intranasal delivery system for esketamine was theorized to be potentially effective due to a “direct knows-two-brain delivery route.”

The current research study is a phase 2 study, and the results were promising enough to lead to phase 3 studies, which are underway.

The original study was posted online by JAMA Psychiatry on 12-27-17. At issue also included an editorial, “The Promise of Intranasal Esketamine As a Novel and Effective Antidepressant.” Reading the full editorial, however, requires either of subscription or purchasing the article. The Medscape article is available online

MHConcierge’s take: about 30% of patients with MDD have symptoms that fit with the TRD pattern. Ketamine, and now intranasal esketamine, continued to be controversial, but as noted by the editors of JAMA psychiatry, and also several professionals who commented on the article, the suicidal risk of T RD probably outweighs the potential risks of ketamine/esketamine. Ketamine has been abused recreationally, but at much higher doses than used for TRD treatment.

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