Comparative safety of prescribed Esketamine and ketamine in relation to renal and urinary disorders: A pharmacovigilance perspective

S Chiappini, A Guirguis, N Schifano, J Corkery, F Semeraro, A Mosca, G D'Andrea, G D Papanti, D Arillotta, G Floresta, G Martinotti, F Schifano

Research output: Contribution to journalArticlepeer-review

Abstract

Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-d-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users. The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine. Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds. The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.

Original languageEnglish
Article number111213
Number of pages15
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume136
Early online date6 Dec 2024
DOIs
Publication statusPublished - 10 Jan 2025

Keywords

  • Esketamine
  • Ketamine
  • Urological safety
  • Pharmacovigilance

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