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Botulinum Toxin

OnabotulinumtoxinA (Botox) is one of the most transformative agents in modern functional urology, with two FDA-approved urologic indications — 100 U intradetrusor for refractory idiopathic overactive bladder (approved 2013) and 200 U intradetrusor for neurogenic detrusor overactivity (approved 2011 in adults, expanded to pediatric patients ≥5 y) — and a broad off-label footprint that includes IC/BPS, detrusor-sphincter dyssynergia (DSD), primary bladder-neck obstruction, pelvic-floor and pudendal myofascial pain, and chronic prostatitis / CPPS.[1][2] It is the only chemodenervation agent with urologic FDA approvals — abobotulinumtoxinA and incobotulinumtoxinA are not interchangeable and carry no urologic labels.

For related classes, see Anticholinergics, β3-agonists, and Topical compounded agents.

Mechanism — why dual efferent + afferent matters​

OnabotulinumtoxinA cleaves SNAP-25, blocking SNARE-complex-mediated vesicle fusion at presynaptic terminals. In the lower urinary tract this produces three simultaneous effects that together explain why BoNT-A improves not just leakage but also urgency, frequency, and pain:[3][4]

PathwayEffect
Efferent (motor)Blocks acetylcholine release at the detrusor neuromuscular junction; blocks ATP release from purinergic efferent nerves — reduces involuntary detrusor contraction
Afferent (sensory)Markedly reduces urothelial ATP release and increases NO release; inhibits release of substance P, CGRP, and glutamate from sensory terminals; downregulates TRPV1 and P2X3 on C-fiber afferents; decreases urothelial NGF
Anti-inflammatoryReduces neurogenic inflammation by suppressing neuropeptide release; modulates mast-cell degranulation

Simple muscle paralysis cannot account for the urgency and pain reductions observed clinically — the afferent effect is a core mechanism, not a byproduct. This is also why liposomal and hydrogel-delivered BoNT-A (which access only the afferent compartment) can improve sensory OAB symptoms without causing retention.[4]

Agents in this class​

AgentFDA urologic indicationUrologic role
OnabotulinumtoxinA (Botox)OAB (100 U), NDO (200 U, ≥5 y)The only approved agent; all urologic data below[1][2]
AbobotulinumtoxinA (Dysport)NoneNot interchangeable with onabotA; no urologic label
IncobotulinumtoxinA (Xeomin)NoneNot interchangeable; no urologic label
RimabotulinumtoxinB (Myobloc)NoneSerotype B; not used in urology

FDA indication #1 — idiopathic OAB (100 U)​

Guideline position​

The AUA/SUFU OAB guideline (2024) places intradetrusor onabotulinumtoxinA alongside sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) as third-line therapy (Statement 25; Moderate Recommendation, Grade A) and now explicitly allows bypassing oral pharmacotherapy in patients who cannot tolerate or do not wish to try antimuscarinics or β3-agonists. Clinicians may offer minimally invasive therapies without requiring trials of behavioral or pharmacologic management (Expert Opinion). PVR must be measured before injection; pivotal RCTs used PVR ≥100–200 mL as exclusion criteria.[5]

Pivotal phase 3 — Nitti 2013​

The registration trial (n = 557 adults with OAB / urge urinary incontinence refractory to antimuscarinics) remains the anchor data:[6]

  • UI reduction: −2.95 episodes/day (onabotA 100 U) vs −1.03 (placebo); p < 0.001
  • Positive treatment benefit: 60.8% vs 29.2% (p < 0.001)
  • Complete continence: 22.9% vs 6.5%
  • Significant improvements across urgency, frequency, nocturia, and QoL (I-QOL, KHQ)
  • Most common AEs: UTI and urinary retention; de novo clean intermittent catheterization (CIC) 5.4% after first treatment

Long-term efficacy — 3.5-year extension​

The open-label extension (Nitti 2016, up to 6 treatments):[7]

  • Consistent mean UI reductions of −3.1 to −3.8 episodes/day across repeat injections
  • Durable symptom and QoL improvement
  • Median duration of effect 7.6 months
  • De novo CIC 4.0% after first treatment, falling to 0.6–1.7% on subsequent treatments
  • No new safety signals; no evidence of tachyphylaxis

Head-to-head vs combined oral pharmacotherapy (Hsieh 2025, RCT, n = 66)​

In women with urodynamically confirmed DO refractory to single pharmacotherapy:[8]

  • OnabotA 100 U and solifenacin 5 mg + mirabegron 25 mg produced equivalent urgency reduction (median 2.0 episodes / 24 h at 12 weeks; p = 0.925)
  • Frequency, nocturia, UUI, and QoL improvements were similar
  • Adverse events (dry mouth, constipation, blurred vision) were significantly more common with combination pharmacotherapy (all p < 0.05)

FDA indication #2 — neurogenic detrusor overactivity (200 U)​

Guideline position​

The AUA/SUFU NLUTD guideline (2021):[9]

  • Statement 40 (Strong Recommendation; Grade A): in NLUTD patients with SCI or MS refractory to oral medications, offer onabotulinumtoxinA to improve storage parameters, decrease incontinence, and improve QoL
  • No efficacy difference between 200 U and 300 U, but a dose-dependent increase in retention risk — 200 U is standard
  • Repeated injections restore first-injection benefit; efficacy does not diminish over time in most patients
  • Statement 41 (Conditional; Grade C): in non-SCI/MS neurogenic patients (PD, CVA, spina bifida), BoNT-A may be offered but evidence is limited

Pivotal phase 3 — MS and SCI​

The registration program (Sanford 2014 review) produced:[10]

  • Significant reductions in UI episodes and MCC increases with matching detrusor-pressure reductions
  • Most common AEs: UTI and urinary retention
  • De novo CIC rate up to 42% (highest in MS patients who were not already on CIC) — this single number drives most of the pre-treatment counseling

Low-dose 100 U for noncatheterizing MS — Tullman 2018​

Class I evidence that 100 U can be used in MS patients who are not already on CIC:[11]

  • UI reduction −3.3 episodes/day vs −1.1 placebo (p < 0.001)
  • De novo CIC substantially lower than with the 200 U regimen
  • Expanded the usable population to patients previously excluded by retention risk

4-year durability — Rovner 2016​

Long-term extension in NDO:[12]

  • Consistent UI reduction −3.4 to −3.9 episodes/day across all 4 years
  • 86.6–94.1% achieved ≥50% UI reduction annually; 43.6–57.4% achieved 100% UI reduction each year
  • I-QOL improvements sustained year-to-year
  • Median duration of effect ≥9.0 months (range 3.0–49.2); ≥26% experienced ≥12-month duration
  • No accumulating safety signal

Personalization (Wang 2026 narrative review)​

Practical levers for NLUTD dosing:[13]

  • Baseline voiding status — patients already on CIC tolerate higher doses with no additional retention penalty
  • Self-catheterization ability — the go / no-go criterion for most non-CIC patients
  • Age — older patients carry higher retention risk
  • Reduced injection-site templates and trigone-inclusive techniques are active areas of investigation

ROSETTA — onabotulinumtoxinA vs sacral neuromodulation​

Amundsen 2016 (JAMA, n = 364 women with refractory UUI) is the landmark head-to-head:[14]

  • UUI reduction: −3.9 (onabotA 200 U) vs −3.3 (SNM) episodes/day — mean difference 0.63 favoring onabotA (p = 0.01)
  • Complete UUI resolution: 20% vs 4% (p < 0.001)
  • UTI higher with onabotA; repeat procedures more common with SNM

Longitudinal fluctuation (Hendrickson 2024) — over 6 months, 61% of onabotA vs 51% of SNM patients maintained persistent objective success. OnabotA had lower 30-day transition probability from success to failure (10% vs 14%; ratio 0.75). Roughly 2 in 5 women's symptoms fluctuated regardless of modality.[15]

2025 network meta (Roman, 12 studies, 2,645 patients) — onabotA reduced UUI more than placebo or SNM; ≥75% UUI reduction was more likely with onabotA. However, complete UUI resolution favored SNM (p < 0.05). Adverse events predictably split — UTI and CIC with BoNT-A; device / reprogramming with SNM.[16]

Crossover — SNM after failed BoNT-A (Yang 2020 meta-analysis) showed 58.5% success, no different from SNM as first-line therapy (RR 0.96; 95% CI 0.72–1.26) — meaningful reassurance that an initial BoNT-A trial does not prejudice subsequent SNM candidacy.[17]

Who does worse? ROSETTA secondary analysis (Richter 2017) — older women with multiple comorbidities and lower baseline QoL had lower response and satisfaction with onabotA vs SNM; higher BMI was associated with reduced odds of achieving ≥50% UUI reduction with either treatment (adjusted OR 0.82 per 5 BMI points).[18]

Injection technique​

Expert consensus — Eilber 2025​

A panel of six high-volume injectors with 100 combined years of experience:[19]

  • Setting — office preferred over hospital / ASC
  • Anesthesia — viscous lidocaine bladder instillation 15 min before injection
  • Reconstitution — 100 U in 5–10 mL normal saline
  • Injection count — 1 to 20 sites is acceptable; fewer injections preferred when equally distributed
  • Technique — start in the lower bladder; slower injection speed improves distribution and reduces discomfort
  • Retreatment — scheduled at 6-month intervals, earlier if symptoms recur, but no sooner than 12 weeks
  • Ceiling — do not exceed 360 U in any 3-month period across all indications (urologic + non-urologic combined)[20]

Standard protocol (Rovner 2014)[20]​

  • All candidates must be willing and able to perform CIC
  • Onset 1–2 weeks; duration 4–10 months
  • Pre-procedure periprocedural antibiotics; consider holding antiplatelet / anticoagulant if clinically appropriate
  • Flexible or rigid cystoscope; ~15-min procedure
  • Follow-up PVR at 7–14 days
  • Trigone sparing is standard for OAB (reduce VUR risk); trigonal inclusion may be used in IC/BPS

Ultrasound-guided transabdominal injection (Li 2025, RCT, n = 64)​

A needle-delivered BoNT-A via transabdominal ultrasound guidance:[21]

  • Equivalent efficacy at 1 and 6 months for urgency, frequency, nocturia, bladder capacity, ICIQ-OAB, OAB-Q
  • Significantly lower complication rate (p < 0.05)
  • Attractive option where cystoscopic capacity is limited or patient preference favors a non-endoscopic approach

Adverse effects and predictors of response​

Adverse effectOAB (100 U)NDO (200 U)Notes
UTI15–35%25–49%Most common; mostly uncomplicated[6][10]
Urinary retention / de novo CIC5.4% first injection → 0.6–1.7% subsequent20–54%Dose-dependent; lower with repeat cycles[7][10]
Elevated PVR~20%Expected in CIC-dependent patientsCheck PVR at 7–14 days[20]
Dysuria, hematuriaCommon, transientCommon, transientProcedure-related[6]
Autonomic dysreflexiaN/ARare in high-SCI patientsMonitor during injection[9]
Systemic weakness / dysphagiaVery rareVery rareUrologic doses well below thresholds reported for large-muscle indications

Predictors of poor response / CIC need — Abrar 2020 (n = 74)[22]​

  • Male sex — the only predictor of poor response (OR 5.45; 95% CI 1.83–16.47; p = 0.002) and also the strongest predictor of CIC need (OR 5.14; p = 0.013)
  • Lower Qmax predicted CIC need (OR 0.91 per mL/s; p = 0.023)
  • Prior hysterectomy in women predicted CIC (OR 4.55; p = 0.038)
  • CIC use predicted UTI (OR 5.26; p = 0.015)

Factors associated with efficacy — Hsiao 2016 (n = 80)[23]​

  • Overall success 63.8%
  • Female sex was the only independent predictor of success (OR 3.75)
  • Low baseline OABSS and OAB-wet predicted better efficacy
  • Low baseline voiding efficiency (<0.67) predicted need for CIC

Biomarker signal — Hanna 2026​

Baseline urinary cytokine profiling suggests older women are less likely to respond; the authors propose pre-treatment cytokine panels as a future selection tool.[24]

Off-label urologic applications​

Interstitial cystitis / bladder pain syndrome​

AUA IC/BPS guideline (2022) — Statement 20 (Option; Grade C): intradetrusor onabotulinumtoxinA may be administered after other treatments have failed; patients must accept the possibility of CIC.[25]

Intratrigonal injection (Pinto 2018, RCT, n = 19) — 10 trigonal injections of 100 U significantly reduced pain vs placebo at week 12 (Δ −3.8 vs −1.6; p < 0.05), with parallel improvements in frequency, urgency, and QoL.[26] Injection-site variability across studies (trigonal, lateral, posterior) and the scarcity of placebo-controlled trials remain the principal interpretive limits — see Intravesical IC/BPS agents for the broader armamentarium.

Detrusor-sphincter dyssynergia​

Goel 2020 systematic review and meta-analysis (11 studies, n = 353):[27]

  • BoNT-A reduces PVR, mean detrusor pressure, DLPP, and urethral pressure in 60–78% of patients at 1 month
  • Most need reinjection at 4–9 months
  • AAN Level B recommendation for onabotulinumtoxinA in DSD[28]

Concomitant detrusor + external urethral sphincter injection (Huang 2022, n = 20 male SCI) — 200 U detrusor + 100 U EUS reduces both maximal detrusor pressure and urethral pressure, raises MCC, and improves QoL without increasing PVR ratio or CIC frequency — a useful construct in SCI patients who want to preserve spontaneous voiding.[29]

Predictors of sphincter-injection success (Lee 2025, n = 207) — overall success 33.8%; DSD grade 1 had 65.7% success vs grade 2 at 14.3% and grade 3 at 7.1%. Higher Qmax and lower PVR predicted response. Patient selection is everything.[30]

Primary bladder-neck obstruction​

Sacco 2014 (n = 30 men) — transurethral 200 U into the bladder neck in medically refractory PBNO dropped IPSS from 21.9 → 7.8 at 2 months (p < 0.001), with durable but reduced benefit at 6 months (10.3).[31]

Lee 2025 (n = 41) — bladder-neck BoNT-A for both neurogenic and non-neurogenic BND yielded 65.9% satisfactory outcomes at 6 months (26.8% successful + 39.0% improved); non-neurogenic BND had the highest satisfaction; higher baseline BOOI predicted failure.[32]

BPH / LUTS — does not work​

Two large phase 2 RCTs are decisive:

  • Marberger 2013 (n = 374) — 100, 200, or 300 U intraprostatic onabotA: IPSS, Qmax, and prostate-volume improvements were matched by placebo, with a large placebo effect from the injectable procedure itself[33]
  • McVary 2014 (n = 315) — 200 U vs placebo: IPSS −6.3 vs −5.6 (no difference) despite a sham-injection run-in designed to suppress placebo response[34]

Phase 3 was not pursued. OnabotulinumtoxinA should not be used for BPH / LUTS outside of study.[35][36]

Chronic prostatitis / CPPS and pelvic-floor myofascial pain​

  • Falahatkar 2015 (RCT, n = 60) — transurethral intraprostatic BoNT-A dropped the NIH-CPSI pain subscale by 64.8% / 75.6% / 80.0% at 1, 3, and 6 months vs no placebo improvement (all p < 0.001) — striking signal but small and unreplicated[37]
  • Franco 2019 Cochrane — intraprostatic BoNT-A may decrease prostatitis symptoms (MD −25.80; low-quality evidence, one trial). Pelvic-floor injection showed little to no effect (MD −2.60; low-quality)[38]
  • Panunzio 2022 pooled meta (18 studies, 896 patients) — benefit across CPPS subtypes (bladder, prostate, gynecologic) but heterogeneity limits firm conclusions[39]

Women — pelvic-floor injection for chronic pelvic pain:

  • Spruijt 2022 systematic review / meta-analysis (8 studies, n = 289 women) — at 24–26 weeks, 15-point VAS reduction for non-menstrual pelvic pain and 13-point reduction for dyspareunia, plus reduced pelvic-floor resting pressure and improved QoL[40]
  • Dessie 2019 RCT (n = 59) — 200 U trigger-point injection was not superior to saline on the primary endpoint (muscle pain on palpation); participants were more likely to report overall improvement at 4 weeks (p = 0.03); de novo constipation 10.1%, incontinence 22%[41]
  • Practical technique (Whitmore 2025) — 200 U in 20 mL saline; inject pubococcygeus, iliococcygeus, and obturator internus using a pudendal nerve kit (1 cm needle depth); effect 3–6 months; pain reduction onset at ~6 weeks; AEs include constipation, incontinence, UTI, retention[42]
  • Overall read (Karp 2025) — numerous uncontrolled series are positive; the few RCTs are equivocal. The evidence is stronger for intraprostatic injection in men than for pelvic-floor injection in women.[43]

See Chronic Pelvic Pain and IC/PBS.

Novel delivery — injection-free approaches​

The dual-compartment mechanism (efferent + afferent) raises an obvious engineering question: can you get BoNT-A into the urothelium without a cystoscopic needle? Three approaches are in development.

Liposome-encapsulated BoNT-A (lipotoxin)​

Liposomes adsorb to and fuse with urothelial cell membranes, delivering toxin across the urothelium without injection — and because the liposomal vehicle does not reach the detrusor, the mechanism is afferent-only, avoiding retention risk.[44][45]

  • Chuang 2014 multicenter RCT (n = 62) — intravesical 200 U lipo-BoNT-A reduced micturitions (Δ −4.64 vs −0.19; p = 0.025) and urgency severity (p = 0.018) vs placebo at 4 weeks, with no retention signal. UUI effects inconclusive.[46]
  • Kuo 2014 pilot RCT (n = 24) — significant frequency and urgency reduction; no PVR or UTI increase; immunohistochemistry showed decreased P2X3 expression in responders.[47]
  • Mechanism contrast (Liu 2015) — injection effectively cleaves SNAP-25 in both urothelium and detrusor; lipotoxin acts in the urothelium only, consistent with the afferent-only clinical profile.[48]

TC-3 thermosensitive hydrogel​

Liquid at room temperature, solid at body temperature — prolongs intravesical dwell time. Early RCT data show frequency, urgency, and incontinence improvement in OAB.[49]

Energy-assisted delivery​

Suprapubic energy shock wave (ESW) after BoNT-A instillation demonstrates cleaved SNAP-25 in bladder tissue on immunohistochemistry — proof-of-concept that ESW can drive toxin across the urothelium. Not clinically deployed.[49]

Status: all three are investigational. The attractive property they share is afferent-selective action, which could extend BoNT-A therapy to patients unwilling or unable to perform CIC.

Special populations​

Pediatric NDO (≥5 y)​

OnabotulinumtoxinA 200 U is FDA-approved for NDO in pediatric patients ≥5 y inadequately managed by or intolerant of anticholinergics — approval extrapolated from adult data with supportive pediatric studies.[1]

Parkinson's disease and post-stroke​

Most authors use 100 U (not 200 U) for PD and post-stroke patients to preserve efficacy while limiting retention — ~20% retention rate keeps post-stroke use largely experimental.[50]

Elderly and men​

Older women with comorbidities had lower response and satisfaction with onabotA compared with SNM in ROSETTA secondary analysis.[18][24] Male OAB patients have a 5-fold higher odds of poor response and a similar odds of CIC need — factor into counseling.[22]

Clinical Positioning​

  • OnabotulinumtoxinA is the only BoNT formulation with urologic FDA approval — 100 U for OAB, 200 U for NDO. Dysport, Xeomin, and Myobloc are not interchangeable and have no urologic label.[1]
  • Efficacy is robust and durable — UUI −2.7 to −3.9 episodes/day; complete continence in 20–57%; median duration 7.6–9.0 months; no tachyphylaxis across 3.5–4 y of repeat injections.[6][7][12]
  • BoNT-A modestly outperforms SNM on UUI reduction, but SNM produces complete UUI resolution more often and is a legitimate first choice in older women with comorbidities. Failed BoNT-A does not prejudice subsequent SNM candidacy.[14][16][17]
  • AUA/SUFU 2024 permits bypassing oral pharmacotherapy — BoNT-A, SNM, and PTNS can be offered as primary third-line options without requiring antimuscarinic or β3 trials first.[5]
  • 100 U expands BoNT-A to noncatheterizing MS patients — Tullman 2018 is Class I evidence; do not reflexively use 200 U when the patient can still void spontaneously.[11]
  • CIC willingness is the gate — every patient counseled for injection must be willing and able to perform CIC. Male sex, hysterectomy history, and low voiding efficiency all raise CIC risk.[20][22]
  • For IC/BPS, BoNT-A is an Option (Grade C) — trigonal 100 U has the best placebo-controlled signal but data remain thin.[25][26]
  • For DSD, AAN Level B — select DSD grade 1 patients; grade 3 has single-digit success.[27][30]
  • For BPH/LUTS, BoNT-A is ineffective — two large phase 2 RCTs are decisive; do not reintroduce this indication.[33][34]
  • For pelvic-floor myofascial pain in women, evidence is equivocal — Spruijt meta-analysis positive, Dessie RCT negative on primary outcome; use as an adjunct to pelvic-floor PT, not a first-line monotherapy.[40][41][43]
  • Schedule retreatment at 6 months, no sooner than 12 weeks. Respect the 360 U / 3-month total-body ceiling across all indications.[19][20]
  • The afferent-only delivery frontier is real — lipotoxin and hydrogel approaches may extend BoNT-A to patients who refuse CIC; follow this literature as it matures.[44][46][47]

See Also​

References​

1. US Food and Drug Administration. Botox (onabotulinumtoxinA) — prescribing information. Accessed via FDA Orange Book.

2. Nitti V, Haag-Molkenteller C, Kennelly M, et al. "Treatment of neurogenic detrusor overactivity and overactive bladder with Botox (onabotulinumtoxinA): development, insights, and impact." Medicine. 2023;102(S1):e32377. doi:10.1097/MD.0000000000032377

3. Lin YH, Chiang BJ, Liao CH. "Mechanism of action of botulinum toxin A in treatment of functional urological disorders." Toxins. 2020;12(2):E129. doi:10.3390/toxins12020129

4. Jiang YH, Liao CH, Kuo HC. "Current and potential urological applications of botulinum toxin A." Nat Rev Urol. 2015;12(9):519–533. doi:10.1038/nrurol.2015.193

5. Cameron AP, Chung DE, Dielubanza EJ, et al. "The AUA/SUFU guideline on the diagnosis and treatment of idiopathic overactive bladder." J Urol. 2024;212(1):11–20. doi:10.1097/JU.0000000000003985

6. Nitti VW, Dmochowski R, Herschorn S, et al. "OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo-controlled trial." J Urol. 2013;189(6):2186–2193. doi:10.1016/j.juro.2012.12.022

7. Nitti VW, Ginsberg D, Sievert KD, et al. "Durable efficacy and safety of long-term onabotulinumtoxinA treatment in patients with overactive bladder syndrome: final results of a 3.5-year study." J Urol. 2016;196(3):791–800. doi:10.1016/j.juro.2016.03.146

8. Hsieh MH, Hwang JC, Su TH, Lau HH. "The efficacy and safety between intradetrusor onabotulinumtoxinA injection and combined pharmacotherapy in patients with refractory overactive bladder: a randomized controlled trial." J Urol. 2025. doi:10.1097/JU.0000000000004660

9. Ginsberg DA, Boone TB, Cameron AP, et al. "The AUA/SUFU guideline on adult neurogenic lower urinary tract dysfunction: treatment and follow-up." J Urol. 2021;206(5):1106–1113. doi:10.1097/JU.0000000000002239

10. Sanford M. "OnabotulinumtoxinA (Botox): a review of its use in the treatment of urinary incontinence in patients with multiple sclerosis or subcervical spinal cord injury." Drugs. 2014;74(14):1659–1672. doi:10.1007/s40265-014-0271-z

11. Tullman M, Chartier-Kastler E, Kohan A, et al. "Low-dose onabotulinumtoxinA improves urinary symptoms in noncatheterizing patients with MS." Neurology. 2018;91(7):e657–e665. doi:10.1212/WNL.0000000000005991

12. Rovner E, Kohan A, Chartier-Kastler E, et al. "Long-term efficacy and safety of onabotulinumtoxinA in patients with neurogenic detrusor overactivity who completed 4 years of treatment." J Urol. 2016;196(3):801–808. doi:10.1016/j.juro.2016.04.046

13. Wang SL, Jaffe WI, Smith AL. "How can we personalize the delivery of onabotulinumtoxin-A for patients with neurogenic lower urinary tract dysfunction?" Neurourol Urodyn. 2026. doi:10.1002/nau.70290

14. Amundsen CL, Richter HE, Menefee SA, et al. "OnabotulinumtoxinA vs sacral neuromodulation on refractory urgency urinary incontinence in women: a randomized clinical trial." JAMA. 2016;316(13):1366–1374. doi:10.1001/jama.2016.14617

15. Hendrickson WK, Zhang C, Jelovsek JE, Nygaard IE, Presson AP. "Longitudinal fluctuations in treatment response after onabotulinumtoxinA and sacral neuromodulation for refractory urgency incontinence." J Urol. 2024;211(1):134–143. doi:10.1097/JU.0000000000003746

16. Roman MP, Ciortea R, Doumouchtsis SK, et al. "Comparison of different treatment outcomes for refractory overactive bladder: a systematic review and meta-analysis." Toxins. 2025;17(10):479. doi:10.3390/toxins17100479

17. Yang G, Xu Y, Qu G, Zhang Y. "Refractory overactive bladder patients who chose sacral neuromodulation therapy after failed onabotulinumtoxinA treatment: a systematic review and meta-analysis." PLoS One. 2020;15(3):e0230355. doi:10.1371/journal.pone.0230355

18. Richter HE, Amundsen CL, Erickson SW, et al. "Characteristics associated with treatment response and satisfaction in women undergoing onabotulinumtoxinA and sacral neuromodulation for refractory urgency urinary incontinence." J Urol. 2017;198(4):890–896. doi:10.1016/j.juro.2017.04.103

19. Eilber KS, Brucker BM, Pezzella A, et al. "Expert opinions on best practices for overactive bladder management with onabotulinumtoxinA." Toxins. 2025;17(4):207. doi:10.3390/toxins17040207

20. Rovner E. "Chapter 6: practical aspects of administration of onabotulinumtoxinA." Neurourol Urodyn. 2014;33 Suppl 3:S32–S37. doi:10.1002/nau.22637

21. Li J, Tang C, Pan H, Song C. "Ultrasound-guided transabdominal botulinum toxin injection for refractory overactive bladder treatment." Sci Rep. 2025;15(1):18162. doi:10.1038/s41598-025-03116-2

22. Abrar M, Stroman L, Malde S, Solomon E, Sahai A. "Predictors of poor response and adverse events following botulinum toxin-A for refractory idiopathic overactive bladder." Urology. 2020;135:32–37. doi:10.1016/j.urology.2019.08.054

23. Hsiao SM, Lin HH, Kuo HC. "Factors associated with therapeutic efficacy of intravesical onabotulinumtoxinA injection for overactive bladder syndrome." PLoS One. 2016;11(1):e0147137. doi:10.1371/journal.pone.0147137

24. Hanna MG, Shah AM, Li W, et al. "Urinary cytokines in predicting intradetrusor onabotulinumtoxin-A response." Neurourol Urodyn. 2026;45(4):845–852. doi:10.1002/nau.70261

25. Clemens JQ, Erickson DR, Varela NP, Lai HH. "Diagnosis and treatment of interstitial cystitis/bladder pain syndrome." J Urol. 2022;208(1):34–42. doi:10.1097/JU.0000000000002756

26. Pinto RA, Costa D, Morgado A, et al. "Intratrigonal onabotulinumtoxinA improves bladder symptoms and quality of life in patients with bladder pain syndrome/interstitial cystitis: a pilot, single-center, randomized, double-blind, placebo-controlled trial." J Urol. 2018;199(4):998–1003. doi:10.1016/j.juro.2017.10.018

27. Goel S, Pierce H, Pain K, et al. "Use of botulinum toxin A (BoNT-A) in detrusor external sphincter dyssynergia (DESD): a systematic review and meta-analysis." Urology. 2020;140:7–13. doi:10.1016/j.urology.2020.03.007

28. Chancellor MB, Elovic E, Esquenazi A, et al. "Evidence-based review and assessment of botulinum neurotoxin for the treatment of urologic conditions." Toxicon. 2013;67:129–140. doi:10.1016/j.toxicon.2013.01.020

29. Huang YH, Chen SL. "Concomitant detrusor and external urethral sphincter botulinum toxin-A injections in male spinal cord injury patients with detrusor overactivity and detrusor sphincter dyssynergia." J Rehabil Med. 2022;54:jrm00264. doi:10.2340/jrm.v54.122

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