Ketamine Research

Accumulating evidence suggests Ketamine is an effective solution for rapid antidepressant effects.
Through randomized trials, Ketamine has shown to have a rapid response, creating a quick release in depression symptoms, however this effect can fade over the following weeks.[1]

More sustained improvement of depression symptoms may occur with repeated infusion.[2],[3] In a randomly assigned, placebo-controlled trial, improvement in symptoms was seen over two weeks compared to placebo.

However, long-term benefits are still unknown. This is due to the short duration of treatment and lack of follow-up in many research studies.

Ketamine has been found to help accelerate response to antidepressant treatment.[4] In a four week-trail of participants who initiated a new antidepressants medication, half were randomly assigned to Ketamine infusion while the other half were assigned to placebo. The Ketamine infusion group created a quicker response time to treatment and did not suffer any noted side effects.
Ketamine has also been found to be a useful short-term treatment for suicidal ideation.[5] Controlling for age, diagnosis, and other current therapies/medications, data from eight randomized trails suggest those who began Ketamine treatment noticed greater improvement within one day of treatment, and more patients (compared to controls) stopped experiencing suicidal ideation by day seven. While improvement began within the first day, the main effects were only noticed in the first week. While ketamine infusion may not be a long-term solution for suicidal individuals, it can create a sense of relief and release that no other medication would be able to.

In a randomized clinical trial with individuals with major depressive disorder exhibiting significant suicidal ideation (N=80), Ketamine infusion therapy was compared with midazolam, a short acting benzodiazepine anesthetic. Those individuals that received Ketamine exhibited a greater reduction in suicidal ideation within 24 hours.[6]

Raid antidepressant effects of Ketamine have been compared with electroconvulsive therapy (ECT) in hospitalized patients with major depressive disorder. In ECT, a brief application of electric stimulus is used to produce a generalize seizure, with the indication of providing relief from mental disorders. Patients that received Ketamine experienced a significant improvement in depressive symptoms after the first dose and throughout all three doses. Ketamine was found to be just as effective as ECT and had a more rapid response to depressive symptoms. [7]

1 Thase, M., & Connolly, K. R. (2018). Unipolar depression in adults: Management of highly resistant (refractory) depression. UptoDate.
2 Malhi GS, Byrow Y, Cassidy F, et al. Ketamine: stimulating antidepressant treatment? BJPsych Open 2016; 2:e5.
3 Vande Voort JL, Morgan RJ, Kung S, et al. Continuation phase intravenous ketamine in adults with treatment-resistant depression.
J Affect Disord 2016; 206:300.
4 Schwartz J, Murrough JW, Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applications. Evid Based Ment Health 2016; 19:35.
5 Wilkinson ST, Ballard ED, Bloch MH, et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry 2018; 175:150.
6 Michael F. Grunebaum, M.D., Hanga C. Galfalvy, Ph.D., Tse-Hwei Choo, M.P.H., John G. Keilp, Ph.D., Vivek K. Moitra, M.D., Michelle S. Parris, B.A., Julia E. Marver, B.A., Ainsley K. Burke, Ph.D., Matthew S. Milak, M.D., M. Elizabeth Sublette, M.D., Ph.D., Maria A. Oquendo, M.D., Ph.D., J. John Mann, M.D. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial.
7 Ghasemi, M., Kazemi, M. H., Yoosefi, A., Ghasemi, A., Paragomi, P., Amini, H., & Afzali, M. H. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder.