Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review

This retrospective chart review (n=27) investigates the efficacy and safety of rapid infusion of esketamine in patients with treatment-resistant depression (TRD) and bipolar depression (BD). The study found that rapid infusion of esketamine is not the best choice for treatment-resistant depression due to tolerability issues. Additionally, patients reported dissociative symptoms ranging from mild to severe and found them to be disturbing.

Abstract

“Background This study evaluated efficacy and safety of intravenous subanesthetic doses of esketamine using an administration time of 10 minutes in patients with treatment-resistant depression and bipolar depression.

Methods A retrospective chart review was conducted to identify patients who met the inclusion criteria for treatment-resistant depression and bipolar depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and these patients received rapid infusion of esketamine between June 2012 and December 2015. The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered to measure and score depressive symptom severity before infusion and at 24 hours, 72 hours, and 7 days after infusion. In addition, Clinical Global Impression scale was administered before and 7 days after esketamine infusion.

Results Esketamine was administered to 30 patients. A total of 27 patients met the inclusion criteria and had MADRS evaluation data, which showed that 23 had unipolar and 4 had bipolar depression. Thirteen patients (48.1%) showed therapeutic response (MADRS reduction ≥50%) within 1 week (7 days) of intervention. Remission (MADRS <7) was observed in 10 patients (37.0%) in the same period. Therapeutic response and remission frequencies were seen in 16 (59.3%) and 11 (40.7%) patients, respectively, within 24 hours following drug infusion. The most relevant side effect observed during the esketamine infusion was dissociative symptoms ranging from mild to severe, which was reported by 11.1% of patients as a very disturbing experience.

Limitations This study was done retrospectively, had a small sample size, and there was no comparative group.

Conclusion The present study demonstrates that rapid infusion of esketamine is possibly not the optimal choice to administer this drug for treatment-resistant depression due to tolerability reasons. Further controlled studies are required to investigate efficacy, safety, and tolerability profiles among the different types of ketamines and methods of using this drug in depressed patients.“

Authors: Fernanda S. Correia-Melo, Felipe C. Argolo, Lucas Araújo-de-Freitas, Gustavo C. Leal, Flávio Kapczinski, Acioly L. Lacerda & Lucas C. Quarantini

Summary

Major depressive disorder is a debilitating mental illness that affects millions of subjects worldwide. Esketamine can be used to treat depression and comorbidities, but it is not suitable for patients with psychotic disorders, previous dissociative disorders, comorbid dementia, substance use disorders, and/or uncontrolled hypertension.

The study was approved by the local Institutional Review Board, and all data were anonymized and kept confidential.

Statistical analysis

A summary of statistical parameters are reported for the MADRS score at each point in time. Quantitative temporal differences among time points were tested, controlling for clinical comorbidities, through a linear mixed effects model.

23 patients with TRD and 4 with bipolar depression were treated with a low-dose of esketamine administered very quickly: time duration 10 minutes. All patients had a high MADRS mean score prior to intervention, and most of them had presented at least 2 failed trials using antidepressants.

Therapeutic response

Thirteen patients (48.1%) displayed therapeutic response and 10 patients (37.0%) displayed remission within 1 week (7 days) after intervention.

The mixed effects model converged to a unique solution, and the time factor was significant. The presence of medical comorbidity was positive, although not significant.

safety

Vital signs, electrocardiograms, and clinical laboratory assessments were within normal ranges, and no deaths occurred in the cases reviewed. Three patients had mild to severe dissociative symptoms.

Discussion

Although the rapid action of NMDA antagonist ketamine in patients with TRD represents a major advance, many questions remain about the efficacy and tolerability of this drug in depressed patients.