Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Course Instructor

Abby Massey

Capstone Semester

Fall 2021

Date of Graduation



Many recent studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to produce antidepressant effects that may be effective in helping reduce treatment-resistant major depression. In particular, three double-blinded randomized control trials have been conducted to assess the viability and effectiveness of this medication for treatment. This systematic literature review will analyze these studies and determine if the overall research indicates that ketamine is useful in improving depression as measured by the Montgomery–Asberg Depression Rating Scale (MADRS)1.

Objective: Assess the effectiveness of IV Ketamine in reducing treatment-resistant major depressive disorder as measured by the Montgomery–Asberg Depression Rating Scale (MADRS)1.

Design: Systematic literature review of three randomized control trials

Methods: Searches were done in PubMed utilizing the terms ketamine, depression, treatment-resistant depression, MADRS, placebo, and Montgomery-Asberg. In PubMed the following limits and terms were used: published in the last 10 years, humans, randomized controlled trial, adults >19 years, and English.

Results: Search criteria found three randomized control trials (RCTs) that met the inclusion/exclusion criteria: Fava et al (2018)2, Murrough et al (2013)3, and Phillips et al (2019)4. Fifteen additional trials were excluded based on the following: trials using esketamine (2), ones analyzing confounding variables (6), using polypharmacy (1), non-applicable studies using search terms (4), or non-blinded (1), and duplicate results (1).

Conclusion: All studies found that ketamine infusions resulted in statistical improvement on the MADRS scale among the trials’ 213 participants in total. Each of the three trials administered ketamine at subanesthetic doses, and they all demonstrated effectiveness. While each of the studies showed improvement over placebo, they also showed improvement when compared to midazolam, and short-acting benzodiazepine. While the improvements were all noted at the 24-hour mark after administration, further study is needed to determine long-term effectiveness and safety.

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