Table 2.

Use in Special Populations

Underlying Psychosis8	Clinical trials have excluded patients with underlying psychosis; thus, there is little data for the administration of intranasal (IN) esketamine in these populations. Use caution in patients with current or prior MDD with psychosis, psychotic disorder, bipolar disorder, or other related disorders. Side effects such as dysgeusia and dissociation may exacerbate underlying psychosis.
Comorbid Substance Use Disorder31	Use caution in patients with a history of substance use disorder(s).
Severe Hypertension or Cardiac Compensation10,31	Monitor BP pre-dose and post-dose in all patients. Caution is warranted in patients with cardiac compensation or severe hypertension. Because the dose of IN esketamine for the treatment of TRD is much lower than the analgesic dose, respiratory depression is less likely to occur. IN esketamine increases BP, predominantly systolic, and increases cardiac output; therefore, medical conditions such as aneurysmal vascular diseases–including thoracic or abdominal aorta, intracranial, and peripheral arterial vessel disease and arteriovenous malformation–are contraindications to IN esketamine use.
Pulmonary Conditions20	The impact of IN esketamine on patients with asthma, COPD, or other pulmonary conditions is unknown. One study on the administration of esketamine via nebulization showed no pulmonary or respiratory adverse events during or after inhalation. It cannot be assumed that IN esketamine will show the same results on pulmonary response. Nasal discomfort, oropharyngeal pain, and throat irritation were reported in the clinical trials.
Pediatric	IN esketamine has not been studied in pediatric populations.
Geriatric27–29	Clinical trials demonstrate that the use of IN esketamine in the geriatric population is safe and effective. Studies in elderly patients ≥ 65 years old with TRD have found significant reduction of MADRS score with only mild-to-moderate side effects, similar to those found in the general population of adults aged 18–64 years. Clinical trials utilized similar dosing regimens, including frequency and dosing, across age groups.
Hepatic and Renal Impairment24	Currently, the hepatic and renal adjustments for IN esketamine are unknown. According to package inserts, no dosage adjustments are needed for intravenous ketamine in hepatic or renal impairment. Individuals with moderate hepatic impairment receiving IN esketamine may show higher area-under-the-curve and half-life values. IN esketamine is not recommended in patients with severe hepatic impairment. Increased frequency of urination was observed in IN-ketamine trials. No recommendations are made regarding impaired renal impairment and there is no clinical experience in patients receiving dialysis treatment.
Pregnancy and Lactation32,33	Use of IN esketamine has not been studied in pregnancy in humans. As animal studies suggest embryofetal toxicity, fetal harm may occur. Both clinician and patient should consider pregnancy planning and prevention if the patient is of childbearing age and has the potential for reproduction. Ketamine may cross the placental barrier and cause maternal complications. Increased uterine tone and uterine contractions/ pressure, ototoxic effects, excessive neonatal muscle tone, apnea, and other complications have been seen with higher dosages of ketamine. Many of these effects may be avoided by using lower dosages of ketamine. Little is known about the use of ketamine with breastfeeding. Refer to the package insert/product labeling for detailed information regarding animal studies with esketamine for more data and possible guidance.