Comparative safety of prescribed Esketamine and ketamine in relation to renal and urinary disorders: A pharmacovigilance perspective.
S Chiappini, A Guirguis, N Schifano, J M Corkery, F Semeraro, A Mosca, G D'Andrea, G Duccio Papanti, D Arillotta, G Floresta, G Martinotti, F Schifano
Progress in neuro-psychopharmacology & biological psychiatry January 10, 2025 DOI: 10.1016/j.pnpbp.2024.111213 via PubMed
Summary
Intranasal esketamine, the S-enantiomer of ketamine, is approved with oral antidepressants for treatment-resistant depression and offers rapid absorption. Analysis of FDA Adverse Events Reporting System data up to May 2024 compared urological safety profiles of esketamine, ketamine, and several other antidepressants and antipsychotics. Risperidone had the highest total adverse drug reactions (107,418) and serious cases (71,515), including acute kidney injury and urinary incontinence. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis showed ketamine had higher odds of renal and urinary disorders, while esketamine had lower or comparable odds, suggesting a relatively favorable tolerability profile for esketamine.
Study at a glance
| Characteristics | Pharmacovigilance analysis Peer reviewed |
|---|---|
| Topics | Ketamine |
| Keywords | Pharmacovigilance Urological safety Drug surveillance Medication safety Bladder safety |
| Citations | 12 |
| Key finding | Esketamine had lower or comparable odds of renal and urinary disorders compared to other antidepressants and antipsychotics, while ketamine had higher odds. |
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.