Esketamine (the s-enantiomer of ketamine) is a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist. A nasal spray formulation has been approved and is to be used in conjunction with an oral antidepressant for treatment-resistant depression (TRD). TRD is defined as a lack of response in the current episode to at least two antidepressant treatments given at adequate doses for an adequate duration.
The efficacy and safety of esketamine nasal spray were evaluated in several short-term (4-week) and longer-term maintenance-of-effect trials. [234] [235] [236] [237] The most common side effects experienced in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk.
Esketamine nasal spray is only available under a Risk Evaluation and Mitigation Strategy (REMS), meaning the patient will have to attend a certified medical office to take the nasal spray; both prescriber and patient must sign a Patient Enrollment Form and after administration, the patient must be monitored for at least 2 hours for sedation, dissociation, suicidal thoughts and behaviors, and because of the potential for drug misuse.
How this approval will affect daily practice remains to be seen. With the logistical challenges of its administration and its side effect profile, trials of combinations of antidepressants and augmentation with lithium or antipsychotics may remain preferred first- and second-line options for TRD.
When prescribing esketamine nasal spray, be aware that patients with poorly controlled hypertension or aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects.
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Psychiatry and Behavioral Sciences
The Johns Hopkins Hospital
Baltimore
MD
DFM declares that he has no competing interests.
Dr Dean F. MacKinnon would like to gratefully acknowledge Dr Roger S. McIntyre, Dr Tonya Fancher, and Dr Richard Kravitz, the previous contributors to this topic.
Director
Residency Training
St Vincent's Hospital
Manhattan
NY
SM declares that he has no competing interests.
Department of Psychiatry and Psychotherapy
Medical University of Vienna
Vienna
Austria
DW has received lecture fees from CSC Pharmaceuticals, GlaxoSmithKline, and Pfizer, and has served as a consultant for GlaxoSmithKline.
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