OPEN Foundation

R. Thomas

Esketamine for treatment resistant depression.


Introduction: Treatment Resistant Depression (TRD) is a common and burdensome condition with poor outcomes and few treatment options. Esketamine is the S-enantiomer of ketamine and has recently been FDA approved in the United States for treating depression that has failed to respond to trials of two or more antidepressants. Areas covered: This review will briefly discuss current treatment options for TRD, then review esketamine. Relevant literature was identified through online database searches, and clinical trial data were provided by Janssen Pharmaceuticals. Pharmacology, including kinetics and dynamics, is discussed, then clinical data regarding efficacy and safety for esketamine from Phase 2-3 trials are reviewed. Expert opinion: In the expert opinion, the authors discuss multiple factors including patient, physician, and social factors that will influence the use of esketamine. While the efficacy of esketamine compared to off-label use of racemic ketamine remains unclear, both esketamine’s approval for use in TRD and longer-term safety data may position it preferentially above racemic ketamine, although factors such as cost and monitoring requirements may limit its use. While questions remain regarding duration and frequency of treatment, as well as addictive potential, esketamine is a novel treatment option offering new hope for TRD.
Swainson, J., Thomas, R. K., Archer, S., Chrenek, C., MacKay, M. A., Baker, G., … & Demas, M. L. (2019). Esketamine for treatment resistant depression. Expert review of neurotherapeutics, 1-13.,
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Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness



Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied.


This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical setting by means of a retrospective, open label, database study. Secondarily, the study will attempt to support previous findings of clinical predictors of effectiveness with intravenous ketamine treatment.


Fifty patients with ultraresistant depression were treated between May 2015-December 2016, inclusive, in two community hospitals in Edmonton using six ketamine infusions of 0.5 mg/kg over 40 min over 2-3 weeks. Data were collected retrospectively from inpatient and outpatient charts. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale score at any point during treatment.


At baseline, the average treatment resistance was severe, with a Maudsley Staging Method score of 12.1 out of 15, 90.0% were resistant to electroconvulsive therapy, and the average Beck Depression Inventory score was 34.2. The response rate was 44% and remission rate was 16%. As a single predictor, moderate or severe anhedonia at baseline predicted a 55% increased likelihood of response. As a combined predictor, this level of anhedonia at baseline with a diagnosis of bipolar depression predicted a 73% increase in likelihood of response.


In a clinical setting, intravenous ketamine showed effectiveness in a complex, severely treatment-resistant, depressed population on multiple medication profiles concurrently. This study gave support to anhedonia and bipolar depression as clinical predictors of effectiveness.

Thomas, R. K., Baker, G., Lind, J., & Dursun, S. (2018). Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness. Journal of psychopharmacology32(10), 1110-1117., 10.1177/0269881118793104
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