The Potential Influence of Associated Antidepressants on the Pharmacokinetic Profile of Esketamine in Patients Affected by Treatment-resistant Depression.
Current neuropharmacology April 7, 2025 Marika Alborghetti, Luana Lionetto, Ginevra Lombardozzi et al. 1 citation
In patients with treatment-resistant depression receiving intranasal esketamine (56 mg) alongside another antidepressant, those taking antidepressants that inhibit cytochrome-P450 isoforms (paroxetine, fluoxetine, duloxetine, venlafaxine) had significantly higher serum esketamine levels 20 minutes after dosing and over 72 hours compared to patients on sertraline, citalopram, escitalopram, or vortioxetine. Salivary esketamine levels were several-fold higher than serum levels at all time points and showed high variability. These pharmacokinetic differences did not affect clinical outcomes, but changes in systolic blood pressure positively correlated with serum esketamine levels, suggesting dose reduction may be warranted for patients with cardiovascular comorbidity on those CYP450-inhibiting antidepressants. Small subgroup sizes limit strong conclusions.