Source / Disclosure
Disclosure: Shelton says it is a consultant or advisory board to Evecxia Therapeutics, Janssen, Neurorx, Novartis Pharmaceuticals Corporation and Seelos Therapeutics, and provides or supports research from Allergan, INmuneBIO, Intracellular Therapies, Janssen, Livenova plc, Neurorx Inc., Novartis Pharmaceuticals Corporation and Otsuka Pharmaceuticals.
Clinical evidence confirms the efficacy of ketamine and esketamine for severe depression and major depressive disorder with suicidal ideation, according to a leading annual meeting of the American Psychiatric Association.
However, there are also limitations and concerns.
“Ketamine is effective for treatment [treatment-resistant depression] and [MDD with suicidal ideation], ” Richard Shelton, MD, director of the University of Alabama at the Birmingham Center for Depression and Suicide, said during the presentation. “Intranasal ketamine has been approved for both indications, although research data are mixed and somewhat contradictory. Our experience with both intravenous and intranasal esketamine has been generally positive, but clinical use is a challenge, and we still believe that most of our patients will need longer treatment. ”
Shelton highlighted the results of double-blind crossover studies, which showed that ketamine gave a rapid and powerful beneficial effect among patients with severe persistent depression. The beneficial effect began within a few hours after ingestion and was maximized after about 1 day. According to Shelton, although ketamine worked among these patients, depression returned within the first week, which led to the spread of studies with single-dose treatment. A 2016 study that conducted twice a week and three times a week intravenous ketamine showed a strong beneficial response, with administration two or three times a week working in much the same way.
The results of a 2018 study comparing placebo and intranasal esketamine 28 mg, 56 mg and 84 mg showed that all three doses worked “quite well” for the treatment of resistant MDD; however, the dose of 84 mg probably had the strongest effect. The powerful and rapid effects of this treatment have led to a breakthrough therapy prescribed by FDA Shelton. Further studies confirmed the approval of esketamine for severe depression in 2019 and MDD with suicidal ideation in 2020.
Shelton also highlighted a paper outlining treatment issues regarding the use of esketamine in depression, which included the possibility that the results of a randomized failure trial were not reliable enough.
On the continuum / timing of treatment, Shelton placed the use of esketamine before re-transcranial magnetic stimulation, monoamine oxidase inhibitors, electroconvulsive therapy, and vagus nerve stimulation, but after SSRIs and SRIs; however, he noted that its placement in the treatment algorithm depends on the local environment and the characteristics of the reimbursement.
“There are problems with reimbursing ketamine for treatment-resistant depression, and I don’t yet know a good way to reimburse an ARI with suicidal intentions,” Shelton said.
RC Shelton. Ketamine for depression: does the excitement last? Mechanisms and evidence. Presented at: Annual Meeting of the American Psychiatric Association; May 1-3, 2021 (Virtual meeting).