From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Patients with a history of vagal response issues should be monitored closely when using esketamine due to its potential cardiovascular effects, as evidenced by the most recent study in 2025 1.
Key Considerations
- Blood pressure and heart rate should be measured before administration and regularly monitored for at least two hours afterward, as esketamine can cause transient increases in blood pressure and heart rate that could trigger vagal responses in susceptible individuals.
- Consider administering esketamine in a reclined position to minimize orthostatic changes and have patients remain seated for at least two hours after administration.
- Start with the lowest effective dose (typically 56 mg intranasally for depression) and adjust based on response and tolerability.
- Have emergency medications and equipment readily available, including atropine for severe bradycardia.
- Patients should avoid food for at least two hours before and liquids for 30 minutes before administration to reduce nausea risk.
Rationale
Esketamine affects the autonomic nervous system, potentially exacerbating vagal tone in predisposed individuals, which could lead to bradycardia, hypotension, or syncope, as suggested by studies in 2020 2 and 2019 3.
Additional Factors
- The pharmacokinetic profile of esketamine may be influenced by associated antidepressants, particularly those that inhibit cytochrome-P450 (CYP450) isoforms, as noted in the 2025 study 1.
- Changes in systolic blood pressure in response to esketamine positively correlated with serum esketamine levels, suggesting a reduction of esketamine dose in patients with cardiovascular comorbidity under treatment with certain antidepressants.
- Heart rate variability (HRV) parameters may be associated with treatment outcome in patients with treatment-resistant depression, as reported in the 2024 study 4.