The Potential Influence of Associated Antidepressants on the Pharmacokinetic Profile of Esketamine in Patients Affected by Treatment-resistant Depression.
Marika Alborghetti, Luana Lionetto, Ginevra Lombardozzi, Luca Montaguti, Giada Trovini, Daniela Donato, Giuseppe Costanzi, Donatella De Bernardini, Federica Catapano, Michele Surano, Ilaria Pagano, Alessia Ceccherelli, Edoardo Bianchini, Giorgio Di Lorenzo, Maurizio Simmaco, Giovanni Martinotti, Georgios D Kotzalidis, Ferdinando Nicoletti, Sergio De Filippis
Current Neuropharmacology April 7, 2025 DOI: 10.2174/011570159X356952241216172603 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 53 |
| Population | Patients with treatment-resistant depression receiving intranasal esketamine |
| Interventions | Esketamine Paroxetine Fluoxetine Duloxetine Venlafaxine Sertraline Citalopram Escitalopram Vortioxetine |
| Dose | 56 mg |
| Topics | Depression Esketamine Ketamine |
| Keywords | Antidepressant drugs Cytochrome p450 isoenzymes. Treatment-resistant Esketamine/ketamine/spravato Antidepressants/ssris/snris/paroxetine Drug-interactions/pharmacokinetics/drug-metabolism/cyp450 |
| Citations | 1 |
| Key findings | Antidepressants that inhibit CYP450 isoforms (paroxetine, fluoxetine, duloxetine, venlafaxine) significantly increase serum esketamine levels, which correlate with systolic blood pressure changes but not clinical outcomes. |
Abstract
Esketamine is administered intranasally in combination with at least another antidepressant in patients with treatment-resistant depression. Some of these antidepressants might affect ketamine's pharmacokinetic profile by inhibiting cytochrome-P450 (CYP450) isoforms. Our aim was to establish how different types of combined antidepressants affect serum and salivary levels of esketamine at the time of maximum plasma concentrations and afterward in TRD patients receiving esketamine in a real-world context. Serum and salivary samples were collected from 53 patients receiving intranasal esketamine (56 mg) at baseline, after 20 min (roughly corresponding to Tmax), 7 hours (corresponding to the t½ value), 24, and 72 hours. Patients were stratified according to the combined antidepressant medication. Salivary esketamine levels were several-fold higher than the corresponding serum levels at all time points, and showed high inter-individual variability. Serum 20-min post-esketamine levels and AUC0-72 levels were significantly higher in patients on antidepressants known to inhibit different isoforms of CYP450 (paroxetine, fluoxetine, duloxetine, venlafaxine), with respect to levels detected in patients on sertraline, citalopram, escitalopram, vortioxetine. These changes in the pharmacokinetic profile of esketamine did not affect the clinical outcome of esketamine. However, 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 paroxetine, fluoxetine, duloxetine, venlafaxine. The CYP450-related status of co-administered antidepressants may affect esketamine levels. However, the small sample sizes of the co-administered drug subgroups and multiple prescriptions do not allow for drawing strong conclusions.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 2
Cites 15
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
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- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
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