Risk of Ketamine Bladder Syndrome in Depression Treatment
The risk of developing ketamine-induced cystitis (KIC) or ketamine bladder syndrome in patients using therapeutic doses of ketamine for treatment-resistant depression appears to be very low, though long-term surveillance data is limited.
Ketamine-Induced Urological Toxicity
- Ketamine-induced cystitis is a well-documented complication in individuals with chronic, heavy recreational ketamine use, presenting with lower urinary tract symptoms (LUTS) including dysuria, increased urinary frequency, urgency, urge incontinence, and hematuria 1
- The FDA label for ketamine specifically mentions that "in individuals with history of chronic ketamine use or abuse, lower urinary tract and bladder symptoms" can occur, along with cystitis (including non-infective, interstitial, ulcerative, erosive and hemorrhagic forms) 1
- Diagnostic studies performed to assess these symptoms have reported cystitis as well as hydronephrosis and reduced bladder capacity in chronic ketamine users 1
Risk Factors and Dose-Dependence
- Ketamine-induced urological toxicity (KIUT) appears to be dose and frequency dependent, with high-frequency ketamine use associated with disruption of the urothelial barrier 2
- Regular ketamine consumption has been shown to increase the risk of cystitis symptoms by 3- to 4-fold in recreational users, who typically use much higher doses than therapeutic protocols 3
- The standard protocol for intravenous ketamine administration in depression treatment is 0.5 mg/kg infused over 40 minutes, which is significantly lower than doses used recreationally 4
Therapeutic Use vs. Recreational Use
- There is currently no evidence that ketamine and/or esketamine treatment at therapeutic doses in adults with mood disorders is associated with KIUT 2
- Only one case report has documented ketamine-induced cystitis in a patient receiving treatment-dose ketamine as part of antidepressant therapy 5
- The pathophysiology of KIC is complicated and involves multiple pathways including direct toxic effects, bladder barrier dysfunction, neurogenic inflammation, and immunoglobulin-E-mediated inflammation 6
Monitoring and Management
- All patients receiving ketamine/esketamine for mood disorder treatment should be queried about genitourinary symptoms during acute and maintenance dosing 2
- Cessation of ketamine use is strongly recommended for all KIC patients and is usually associated with improvement of symptoms 3, 7
- Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage 5
Treatment Options for KIC
- First-line treatment is always cessation of ketamine use 6, 7
- Medical treatments that may help in early KIC include oral anti-inflammatories and intravesical treatments such as hyaluronic acid installation 6
- For severe cases with irreversible pathological changes like contracted bladder, surgical interventions including augmentation enterocystoplasty might be necessary 6
Conclusion
While ketamine has shown promising results for treatment-resistant depression and suicidal ideation 8, 4, patients and clinicians should be aware of the potential risk of urological complications, even though this risk appears to be minimal at therapeutic doses. The benefits of ketamine treatment for severe depression must be weighed against this potential risk, with regular monitoring for early signs of urological symptoms.