THE ASSOCIATION BETWEEN KETAMINE AND ESKETAMINE AND UROLOGICAL SYMPTOMS: REPORTS TO THE FOOD AND DRUG ADMINISTRATION ADVERSE EVENT REPORTING SYSTEM (FAERS)

Background

Chronic recreational use of ketamine has been associated with urological complications, such as ketamine-induced cystitis (i.e., bladder inflammation, sometimes referred to as “ketamine bladder”). Cystitis results from the toxic effects of ketamine and its metabolites, which cause inflammation, fibrosis and shrinking of the bladder. Symptoms include increased urinary frequency and urgency, dysuria, hematuria and urinary incontinence. It remains unclear the level of risk associated with ketamine/esketamine when prescribed at the dose and frequency used for depression.

Methods

The Food and Drug Administration Adverse Event Reporting System (FAERS) database was searched from inception to March 2026 for reports of urological symptoms. MedDRA terms related to bladder inflammation and lower urinary tract symptoms (LUTS) were utilized. Reporting odds ratios (ROR) were calculated with corresponding 95% confidence intervals (95% CIs). Selective serotonin and serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI) was used as the comparator. Z-statistics were calculated to determine the disproportionality of the RORs. Utilizing bayesian information component (IC) values, the corresponding lower limits of the 95% CI were calculated (IC025).

Results

Compared with SSRI/SNRIs, ketamine showed disproportionate reporting for all specified bladder inflammation outcomes, including cystitis (593 vs. 221 reports; ROR = 21.18, 95% CI [18.13, 24.75]; z = 38.42, p < 0.001; IC025 = 3.67). Ketamine was also disproportionately associated with LUTS, including micturition urgency (447 vs. 30 reports; ROR 3.74, 95% CI [2.58, 5.42]; z = 6.99, p = 2.8010-12; IC025 = 1.16), bladder pain (120 vs. 6 reports; ROR 2.78, 95% CI [1.23, 6.32]; z = 2.45, p = 1.4410-2; IC025 = -0.16), and dysuria (1726 vs. 58 reports; ROR 1.87, 95% CI [1.44, 2.44]; z = 4.69, p = 2.6810-6; IC025 = 0.43). With respect to esketamine, disproportionate reports were observed with interstitial cystitis (55 vs 11 reports; ROR = 6.57, 95% CI [3.44, 12.56]; z = 5.70; p < 0.001; IC025 = 1.21). Nonsignificant associations between esketamine and cystitis, noninfective cystitis, haemorrhagic cystitis and chemical cystitis were observed. Mixed results were observed with respect to whether esketamine is disproportionately associated with LUTS. Esketamine was disproportionately associated with micturition urgency (447 vs 39 reports; ROR 2.87, 95% CI [2.07, 3.98]; z = 6.31; p < 0.001) and bladder pain (120 vs 11 reports; ROR 3.01, 95% CI [1.62, 5.58]; z = 3.50, p < 0.05). In contrast, compared to SSRI/SNRIs, esketamine was disproportionately associated with lower odds of dysuria (1726 vs 10 reports; ROR 0.19, 95% CI [0.10, 0.35]; z = -5.24, p < 0.001; IC025 = -3.38).

Conclusion

Available pharmacovigilance data suggest disproportionate reporting of cystitisspectrum adverse events and LUTS for ketamine relative to SSRI/SNRI comparators. Esketamine showed no clear cystitis-spectrum signal and mixed LUTS associations. These findings warrant cautious interpretation and further investigation given the limitations of spontaneous reporting and the substantially smaller ketamine and esketamine report base compared with the pooled comparator group. Clinically, these findings may support greater vigilance and routine screening for urinary-related adverse events in patients receiving ketamine.