Table Info

Table 1.

Cardiovascular effects of esketamine: summary of clinical and preclinical studies

Study	Population/Model	Esketamine dosage	Key findings	Cardiovascular effects	Recommendations
2020 study (esketamine in TRD patients)	70 patients with treatment-resistant depression	0.5–1.0 mg/kg (subcutaneous)	BP increases after each injection, transient hypertension in 14 patients	Slight BP increase (peak 4.87/5.54 mmHg), transient hypertension (SBP > 180 mmHg, DBP > 110 mmHg)	BP monitoring recommended for 90 minutes post-injection
2021 study (tranylcypromine + esketamine)	43 patients with major depressive episodes, 14 of whom concomitantly received tranylcypromine	0.25–0.5 mg/kg	No significant increase in BP or HR, stable hemodynamics	Minimal adverse effects, no significant cardiovascular risks with monitoring	Continuous monitoring recommended
2024 preliminary study (HRV and ESK-NS)	18 patients with TRD	ESK-NS	Responders had lower HRV at baseline, increased HRV after one month	HRV could predict treatment response (AUC = 0.844)	Further research on HRV as an electrophysiological marker for personalized treatment in TRD
2022 study (esketamine in guinea pigs)	Guinea pigs	0.125, 0.25, 0.5 mg·kg⁻¹·h⁻¹	Dose-dependent changes in heart electrophysiology, altered resting membrane potential, action potential amplitude and duration	Prolonged action potentials at higher doses, increased HR at lower doses, altered Connexin43 expression	Caution for potential arrhythmias, especially at higher doses
2024 study (zebrafish larvae)	Zebrafish embryos	Varying concentrations of esketamine	Decreased HR, stroke volume, and cardiac output	Impact on cardiac development genes, reduced cardiac function	Implications for cardiovascular safety, especially in patients with underlying conditions

AUC: area under the curve; BP: blood pressure; DBP: diastolic BP; ESK-NS: esketamine nasal spray; HR: heart rate; HRV: HR variability; SBP: systolic BP; TRD: treatment-resistant depression

Declarations

Acknowledgments

The authors would like to thank the Summer Internship Program and Anesthesia Research Center (ARC) from the Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital (MGH) for their valuable support.

Author contributions

ES and YL: Resources, Data curation, Writing—original draft. JW: Conceptualization, Validation, Supervision, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

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