Skip to main content

Gabapentinoids

Gabapentinoids (gabapentin and pregabalin) are α2δ-1 voltage-gated calcium channel ligands originally developed as anticonvulsants and now widely used for neuropathic pain and neuromodulation. In urology they are deployed across seven off-label applications — chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS), interstitial cystitis / bladder pain syndrome (IC/BPS), chronic pelvic pain in women, neurogenic detrusor overactivity, MS-related spasticity with secondary bladder effects, ureteral stent-related symptoms, perioperative pain in urologic surgery, and (investigationally) premature ejaculation. None of these are FDA-approved. Gabapentinoids also produce clinically important urologic adverse effects — sexual dysfunction in up to 41% of pregabalin users and case-confirmed urinary incontinence — that are routinely under-recognized.[1][2][3]

For the broader pelvic-pain framework, see Chronic Pelvic Pain. For other classes used in pelvic pain, see Neuropathic & Pelvic Pain pharmacology.

Mechanism — Why It Matters in Urology​

Gabapentinoids bind the α2δ-1 subunit of voltage-gated calcium channels in the CNS, reducing calcium-dependent release of excitatory neurotransmitters and decreasing neuronal excitability.[4] Several sites are urologically relevant:

  • Spinal dorsal horn — reduces afferent bladder signaling (pain, urgency) by inhibiting excitatory transmitter release from primary afferent terminals[5][6]
  • Locus coeruleus — activates a descending noradrenergic analgesic pathway for bladder pain (a mechanism distinct from the micturition-modulating one)[5]
  • Sacral spinal cord — modulates the micturition reflex arc, decreasing detrusor overactivity by reducing interneuron excitability[7]
  • Anti-inflammatory effect — pregabalin reduces NF-κB pathway activation and pro-inflammatory cytokine production in cystitis models, suggesting a direct anti-inflammatory contribution beyond pure neuromodulation[6]

In preclinical cystitis models, gabapentinoids reduce both bladder pain and voiding frequency, but through different mechanisms — analgesia via descending noradrenergic pathway, micturition effects via spinal mechanism.[5]

Urologic Applications at a Glance​

ApplicationAgentBest evidencePractical position
CP/CPPSPregabalin, gabapentinRCT (pregabalin); retrospective comparison favoring gabapentin[8][9]May be considered as part of multimodal therapy[8]
IC/BPSGabapentin, pregabalinExtrapolated from neuropathic pain; no IC-specific RCTs[11]AUA Clinical Principle for non-narcotic pain management
Chronic pelvic pain (women)Gabapentin, pregabalinGaPP2 RCT — negative; ACOG Level B based on neuropathic-pain extrapolation[10][12]Not first-line; reserve for clearly neuropathic phenotype
Neurogenic detrusor overactivityGabapentinPediatric RCT; adult open-label[13][7]Adjunct or alternative when anticholinergic-intolerant
MS spasticity (with bladder effects)GabapentinSpasticity RCTs; consensus guidelines[14][23][24]First-line antispasticity option in MS
Ureteral stent symptoms (pain)PregabalinNetwork meta-analysis (best for pain domain in combination)[15]Adjunct to alpha-blocker / anticholinergic
Perioperative urologic painGabapentin, pregabalinAnesthesiology meta — no clinically significant benefit; URS RCT — increased pain[16][17]Not recommended routinely
Premature ejaculationPregabalinSingle RCT[18]Investigational; not in guidelines

CP/CPPS — the most-studied urologic indication​

Pregabalin RCT (Pontari) and Cochrane​

In 6-week pregabalin (n = 218) vs placebo (n = 106) for CP/CPPS:[8][19][20]

  • Primary endpoint (≥ 6-point NIH-CPSI improvement): 47.2% vs 35.8%, p = 0.07 — failed
  • Secondary outcomes: mean NIH-CPSI better with pregabalin (MD −2.4, p = 0.01); pain domain MD −1.0 (p = 0.04); urinary symptoms MD −0.70 (p = 0.02); QoL MD −0.70 (p = 0.01)
  • GRA moderate / marked improvement: 31.2% vs 18.9% (p = 0.02)

The Cochrane review concludes pregabalin produces "little to no difference" in prostatitis symptoms vs placebo (high-certainty evidence).[19]

Gabapentin vs pregabalin (retrospective)​

In 119 men with UCPPS, gabapentin alone outperformed pregabalin alone:[9]

  • ≥ 50% pain improvement: 75.8% (gabapentin) vs 40% (pregabalin) (p = 0.0012; NNT 2.9)
  • 20 patients failed pregabalin and were switched to gabapentin
  • Need for adjunctive amitriptyline: 13.6% vs 44% (p = 0.0001; NNT 4)
  • Limitation: retrospective, non-randomized

Clinical interpretation​

The 2025 JAMA Prostatitis review notes pregabalin "may be considered" as analgesic therapy in CP/CPPS, with the caveat that opioids should be avoided.[8] Practical bottom line: a time-limited gabapentinoid trial — gabapentin first based on the Agarwal data, pregabalin as second-line — is reasonable for the neuropathic / pelvic-floor pain phenotype, with explicit stop rules if no benefit at 4–6 weeks.

IC/BPS​

There are no IC/BPS-specific RCTs. Use rests on extrapolation from neuropathic-pain evidence and the central-sensitization model.[11]

  • The 2022 AUA IC/BPS Guideline addresses pharmacological pain management as a Clinical Principle: management should mirror other chronic-pain conditions and prefer non-opioids — gabapentinoids fit under this umbrella but are not specifically named[11]
  • Preclinical evidence is strong — gabapentinoids reduce bladder pain behaviors and voiding frequency in LPS-induced chronic cystitis; α2δ-1 is upregulated in spinal dorsal horn and locus coeruleus in cystitis models; mirogabalin shows longer-lasting analgesic effects in models[5][6]
  • Practical use: off-label as part of multimodal analgesia, particularly when neuropathic features (allodynia, hyperalgesia, multiple overlapping pain conditions) are prominent

Chronic Pelvic Pain in Women​

ACOG Level B vs the GaPP2 trial​

ACOG (2020) recommends gabapentin and pregabalin for neuropathic chronic pelvic pain based on extrapolation.[10][21]

The GaPP2 multicentre RCT (n = 306) of gabapentin titrated to 2,700 mg/day (900 mg TID) over 16 weeks for women with chronic pelvic pain and no obvious pelvic pathology was negative:[12]

  • No significant difference in worst-pain NRS at 16 weeks vs placebo
  • Investigators' conclusion: "no further research is required to establish the role of gabapentin in the management of chronic pelvic pain in women with no obvious pelvic pathology"

Practical interpretation​

The high-quality RCT evidence is against routine gabapentin for undifferentiated CPP. Reserve for the subgroup with clearly neuropathic features (allodynia, dermatomal distribution, response to lidocaine challenge), with a defined trial duration and stop rule.

Neurogenic Detrusor Overactivity​

Pediatric RCT (spina bifida, n = 44)​

Gabapentin vs oxybutynin vs the combination:[13]

  • All three groups improved symptoms and urodynamics
  • Best response in the combination group
  • Gabapentin better tolerated than oxybutynin (fewer anticholinergic effects)
  • Conclusion: gabapentin is "a good alternative to oxybutynin … both as monotherapy and as add-on"

Adult open-label (n = 16)​

Gabapentin (31 days) in neurogenic OAB significantly modified urodynamic indices (especially detrusor overactivity), reduced irritative symptom scores and frequency, with no patient discontinuing for AEs.[7]

Preclinical​

In a rat model of neurogenic detrusor overactivity after spinalization, both pregabalin and lamotrigine improved baseline pressure, detrusor pressure at maximum capacity, capacity, and the frequency of overactivity.[22]

Clinical role​

Reasonable add-on or alternative for patients who tolerate anticholinergics poorly. Not in the AUA neurogenic-bladder guideline.

MS Spasticity with Secondary Bladder Effects​

Gabapentin is a first-line antispasticity option in MS (with baclofen and tizanidine).[14][23][24][25]

  • A placebo-controlled crossover RCT (n = 21) of gabapentin 900 mg TID significantly reduced Modified Ashworth Scale scores, spasm severity, interference with function, and painful spasms — without worsening concentration or fatigue, a recognized advantage over baclofen and tizanidine[14]
  • An earlier crossover study (n = 15) at 400 mg TID also improved Ashworth, Visual Faces, and Kurtzke scores[25]

Urologic relevance: the same spinal-cord mechanisms that drive limb spasticity also contribute to detrusor overactivity and DSD in MS. Gabapentin's antispasticity effect may produce secondary benefits for neurogenic LUTS in MS, though this has not been systematically tested.

Ureteral Stent–Related Symptoms​

A Bayesian network meta-analysis (26 RCTs) of pharmacologic management of stent symptoms found that for the pain domain, the most effective class was combined anticholinergic + pregabalin.[15]

  • For urinary symptoms, sexual performance, general health, and work performance, the best classes were combined α-blocker + anticholinergic and PDE5 inhibitors
  • The most effective single combination for pain was silodosin 8 mg + solifenacin 10 mg
  • Pregabalin's role is as a pain-domain adjunct, not stent-symptom monotherapy[15][26]

Perioperative Use in Urologic Surgery​

Gabapentinoids have been incorporated into many ERAS protocols, but recent evidence has tempered enthusiasm.

Anesthesiology meta-analysis (281 RCTs, N = 24,682)[16]​

  • Reduced postoperative pain at 6, 12, 24, and 48 h, but below the minimally important difference (10/100) at every time point
  • No effect on subacute or chronic pain prevention
  • Lower PONV but more dizziness and visual disturbance
  • "Results do not support the routine use of pregabalin or gabapentin" for postoperative pain in adults

Ureteroscopy-specific RCT (n = 118)[17]​

Single-dose perioperative pregabalin 300 mg vs placebo for URS:

  • Postoperative pain scores higher with pregabalin (3.7 vs 2.0; p = 0.004)
  • No difference in cognition or AEs
  • "Urologists should not routinely use this adjunctive medication in ureteroscopy"

Older adults​

Park et al. found perioperative gabapentin in older adults undergoing major surgery was associated with increased in-hospital adverse events (delirium, respiratory depression), particularly with concurrent opioids; AGS Beers Criteria lists gabapentin as potentially inappropriate in older adults.[27]

Bottom line​

Routine perioperative use in urologic surgery is not supported.[16][28][29][38]

Premature Ejaculation (Investigational)​

A single double-blind, placebo-controlled RCT (n = 116) of on-demand pregabalin:[18]

  • 150 mg pregabalin 1–2 h before intercourse improved IELT vs placebo
  • 75 mg showed no effect
  • Small, short-term (2 weeks)
  • Conclusion: "promising drug for additional evaluation"

Pregabalin is not in current PE guidelines, and the mechanism is more likely a side-effect (delayed ejaculation) than a therapeutic effect.[18][30]

Idiopathic OAB (Limited Evidence)​

A multicenter randomized double-blind crossover (n = 519 treatment periods) in women with idiopathic OAB:[31]

  • Pregabalin 150 mg BID alone significantly increased mean voided volume vs tolterodine ER alone (27.4 vs 15.5 mL, p = 0.005) and vs placebo (11.9 mL, p = 0.0006)
  • Pregabalin + tolterodine ER showed the largest improvement (39.5 vs 15.5 mL for tolterodine alone)

Practical interpretation: pregabalin may offer adjunctive benefit in idiopathic OAB, but this is not in any guideline and has not been replicated.[32]

Urologic Adverse Effects — Frequently Missed​

Gabapentinoids cause clinically important urologic AEs, particularly when prescribed for non-urologic indications in patients with pre-existing LUTS.

Pregabalin (FDA label — urogenital system)[3]​

  • Frequent: anorgasmia, impotence, urinary frequency, urinary incontinence
  • Infrequent: abnormal ejaculation, dysuria, hematuria, kidney calculus, oliguria, urinary retention
  • Rare: acute kidney failure, epididymitis

Gabapentin (FDA label — postmarketing)[2][33]​

Breast enlargement, libido changes, ejaculation disorders, anorgasmia.

Sexual dysfunction is common​

A case series (n = 75) on pregabalin found 41.3% sexual dysfunction:[34]

  • ED 51.6%, anorgasmia 32.3%, low libido 35.5%
  • Onset within weeks; not dose-related (occurs even at 50–100 mg/day)
  • Resolves within weeks of discontinuation

Gabapentin-induced sexual dysfunction is reported at doses as low as 300 mg/day, including total sexual dysfunction (loss of libido, anejaculation, anorgasmia, impotence).[35]

Urinary incontinence​

Case reports document gabapentin-associated urinary incontinence verified by rechallenge — onset within 1 day of initiation, resolution within 2 days of discontinuation.[36] A pharmacovigilance analysis of FAERS identified neuropsychiatric drugs (including gabapentinoids) among independent risk factors for drug-induced urinary incontinence; over half of cases occurred within 30 days of medication initiation.[37]

Pragmatic point: ask about gabapentinoid use in any patient presenting with new-onset incontinence or sexual dysfunction.

Practical Prescribing for Urologists​

IndicationTypical dose
CP/CPPSGabapentin 300–900 mg TID (titrate over 1–2 weeks); pregabalin 75–150 mg BID[8][9]
IC/BPSGabapentin 300–1,200 mg TID as part of multimodal analgesia
Neurogenic OABGabapentin 300–900 mg TID[7][13]
Stent-related painPregabalin 75–150 mg BID as adjunct to alpha-blocker / anticholinergic[15]

Cross-cutting precautions​

  • Renal excretion — dose adjustment for renal impairment by CrCl; particularly relevant in obstructive uropathy or post-nephrectomy[2]
  • Opioid co-administration — increased respiratory depression; FDA boxed warning for gabapentin with opioids[2]
  • Older adults — sedation, falls, delirium; AGS Beers Criteria lists gabapentin as potentially inappropriate[27]
  • Abuse potential — pregabalin is a Schedule V controlled substance; misuse increases in patients with opioid use disorder[1][4]
  • Withdrawal — abrupt discontinuation can cause seizures, anxiety, insomnia, nausea; taper over ≥ 1 week[2]

Clinical Positioning​

  • Every urologic use of gabapentinoids is off-label, and most rest on small studies, extrapolation, or preclinical models[1]
  • CP/CPPS has the strongest urologic dataset — a time-limited trial of gabapentin (then pregabalin) is reasonable for the neuropathic / pelvic-floor phenotype with explicit stop rules
  • Chronic pelvic pain in women — the GaPP2 RCT was negative; reserve for clearly neuropathic phenotype, not undifferentiated CPP[12]
  • Neurogenic OAB — useful add-on or alternative when anticholinergics are poorly tolerated, particularly in pediatrics[13]
  • MS — first-line antispasticity option with potential secondary bladder benefit[14][23]
  • Stent symptoms — pregabalin as a pain-domain adjunct, not monotherapy[15]
  • Perioperative urologic surgery — not recommended routinely; the URS RCT actually found higher pain with pregabalin[16][17]
  • Sexual dysfunction and incontinence are frequently missed AEs — ask about gabapentinoid use in new-onset cases[34][36]
  • The Goodman & Brett JAMA Internal Medicine overview is direct: "the evidence to support off-label gabapentinoid use for most painful clinical conditions is limited" — discontinue when patients perceive little or no benefit[1]

See Also​

References​

1. Goodman CW, Brett AS. "A clinical overview of off-label use of gabapentinoid drugs." JAMA Intern Med. 2019;179(5):695–701. doi:10.1001/jamainternmed.2019.0086

2. US Food and Drug Administration. Gabapentin — prescribing information. Updated 2025-05-23.

3. US Food and Drug Administration. Pregabalin — prescribing information. Updated 2025-12-09.

4. Finnerup NB. "Nonnarcotic methods of pain management." N Engl J Med. 2019;380(25):2440–2448. doi:10.1056/NEJMra1807061

5. Yoshizumi M, Kitano Y, Watanabe C, Sakurada S, Mizoguchi H. "Characterization of actions of the novel gabapentinoid drug mirogabalin on painful bladder hypersensitivity in rats with lipopolysaccharide-induced chronic cystitis." Life Sci. 2025:123942. doi:10.1016/j.lfs.2025.123942

6. Boudieu L, Mountadem S, Lashermes A, et al. "Blocking α2δ-1 subunit reduces bladder hypersensitivity and inflammation in a cystitis mouse model by decreasing NF-κB pathway activation." Front Pharmacol. 2019;10:133. doi:10.3389/fphar.2019.00133

7. Carbone A, Palleschi G, et al. "Gabapentin treatment of neurogenic overactive bladder." Clin Neuropharmacol. 2006;29(4):206–214. doi:10.1097/01.WNF.0000228174.08885.AB

8. Borgert BJ, Wallen EM, Pham MN. "Prostatitis." JAMA. 2025;334(11):1003–1013. doi:10.1001/jama.2025.11499

9. Agarwal MM, Elsi Sy M. "Gabapentenoids in pain management in urological chronic pelvic pain syndrome: gabapentin or pregabalin?" Neurourol Urodyn. 2017;36(8):2028–2033. doi:10.1002/nau.23225

10. American College of Obstetricians and Gynecologists. "Chronic pelvic pain: ACOG Practice Bulletin, Number 218." Obstet Gynecol. 2020;135(3):e98–e109. doi:10.1097/AOG.0000000000003716

11. 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

12. Horne AW, Vincent K, Hewitt CA, et al. "Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial." Lancet. 2020;396(10255):909–917. doi:10.1016/S0140-6736(20)31693-7

13. Dash V, Bawa M, Mahajan JK, et al. "Role of gabapentin and anticholinergics in management of neurogenic bladder after repair of spina bifida — a randomized controlled study." J Pediatr Surg. 2016;51(12):2025–2029. doi:10.1016/j.jpedsurg.2016.09.030

14. Cutter NC, Scott DD, Johnson JC, Whiteneck G. "Gabapentin effect on spasticity in multiple sclerosis: a placebo-controlled, randomized trial." Arch Phys Med Rehabil. 2000;81(2):164–169. doi:10.1016/s0003-9993(00)90135-7

15. Hinojosa-Gonzalez DE, Segall MR, Eisner BH. "Pharmacological management of ureteral stent-related symptoms: a systematic review, Bayesian network meta-analysis, and meta-regression." J Urol. 2023;210(5):739–749. doi:10.1097/JU.0000000000003616

16. Verret M, Lauzier F, Zarychanski R, et al. "Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis." Anesthesiology. 2020;133(2):265–279. doi:10.1097/ALN.0000000000003428

17. Rosen GH, Hargis PA, Kahveci A, et al. "Randomized controlled trial of single-dose perioperative pregabalin in ureteroscopy." J Urol. 2023;210(3):517–528. doi:10.1097/JU.0000000000003572

18. El Najjar MR, El Hariri M, Ramadan A, Hefny Hashem AA. "A double blind, placebo controlled, randomized trial to evaluate the efficacy and tolerability of on-demand oral pregabalin (150 mg and 75 mg) in treatment of premature ejaculation." J Sex Med. 2020;17(3):442–446. doi:10.1016/j.jsxm.2019.12.014

19. Franco JV, Turk T, Jung JH, et al. "Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome." Cochrane Database Syst Rev. 2019;10:CD012552. doi:10.1002/14651858.CD012552.pub2

20. Aboumarzouk OM, Nelson RL. "Pregabalin for chronic prostatitis." Cochrane Database Syst Rev. 2012;(8):CD009063. doi:10.1002/14651858.CD009063.pub2

21. Arnold MJ, Osgood AT, Aust A. "Chronic pelvic pain in women: ACOG updates recommendations." Am Fam Physician. 2021;103(3):186–188.

22. Loutochin O, Al Afraa T, Campeau L, et al. "Effect of the anticonvulsant medications pregabalin and lamotrigine on urodynamic parameters in an animal model of neurogenic detrusor overactivity." Neurourol Urodyn. 2012;31(7):1197–1202. doi:10.1002/nau.21214

23. Gold R, Oreja-Guevara C. "Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines." Expert Rev Neurother. 2013;13(12 Suppl):55–59. doi:10.1586/14737175.2013.865880

24. Haas J. "Pathophysiology, assessment and management of multiple sclerosis spasticity: an update." Expert Rev Neurother. 2011;11(4 Suppl):3–8. doi:10.1586/ern.11.25

25. Mueller ME, Gruenthal M, Olson WL, Olson WH. "Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis." Arch Phys Med Rehabil. 1997;78(5):521–524. doi:10.1016/s0003-9993(97)90168-4

26. Koprowski C, Kim C, Modi PK, Elsamra SE. "Ureteral stent-associated pain: a review." J Endourol. 2016;30(7):744–753. doi:10.1089/end.2016.0129

27. Park CM, Inouye SK, Marcantonio ER, et al. "Perioperative gabapentin use and in-hospital adverse clinical events among older adults after major surgery." JAMA Intern Med. 2022;182(11):1117–1127. doi:10.1001/jamainternmed.2022.3680

28. Patel AS, Abrecht CR, Urman RD. "Gabapentinoid use in perioperative care and current controversies." Curr Pain Headache Rep. 2022;26(2):139–144. doi:10.1007/s11916-022-01012-2

29. Kumar AH, Habib AS. "The role of gabapentinoids in acute and chronic pain after surgery." Curr Opin Anaesthesiol. 2019;32(5):629–634. doi:10.1097/ACO.0000000000000767

30. Raisi F, Soleimani R, Ahmadzadeh A, et al. "Efficacy and safety of pharmacological treatments in patients with premature ejaculation: an umbrella review of meta-analyses of randomized controlled trials." J Sex Med. 2025;22(6):1014–1023. doi:10.1093/jsxmed/qdaf094

31. Marencak J, Cossons NH, Darekar A, Mills IW. "Investigation of the clinical efficacy and safety of pregabalin alone or combined with tolterodine in female subjects with idiopathic overactive bladder." Neurourol Urodyn. 2011;30(1):75–82. doi:10.1002/nau.20928

32. Roberts K, Dao A, Alfahmy A, Mitchell D, Sheyn D. "Does gabapentin impact response to anticholinergics for overactive bladder?" Int Urogynecol J. 2022;33(9):2501–2506. doi:10.1007/s00192-022-05231-4

33. US Food and Drug Administration. Gabapentin — postmarketing prescribing information. Updated 2025-04-12.

34. Hamed SA. "Sexual dysfunctions induced by pregabalin." Clin Neuropharmacol. 2018;41(4):116–122. doi:10.1097/WNF.0000000000000286

35. Kaufman KR, Struck PJ. "Gabapentin-induced sexual dysfunction." Epilepsy Behav. 2011;21(3):324–326. doi:10.1016/j.yebeh.2011.04.058

36. Rissardo JP, Caprara ALF. "Gabapentin-associated urinary incontinence: a case verified by rechallenge." Clin Neuropharmacol. 2019;42(3):91–93. doi:10.1097/WNF.0000000000000334

37. Li C, Wu C, Cai S, Wang L. "Pharmacovigilance evidence of drug induced urinary incontinence in the FDA Adverse Event Reporting System." Sci Rep. 2025;15(1):38278. doi:10.1038/s41598-025-23379-z

38. Wick EC, Grant MC, Wu CL. "Postoperative multimodal analgesia pain management with nonopioid analgesics and techniques: a review." JAMA Surg. 2017;152(7):691–697. doi:10.1001/jamasurg.2017.0898