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Imipramine

Imipramine is a tertiary-amine tricyclic antidepressant (TCA) with an FDA-labeled urologic indication for temporary adjunctive therapy for childhood nocturnal enuresis in patients ≥ 6 years; historical literature also describes off-label use for overactive bladder, stress urinary incontinence, mixed urinary incontinence, and, less often, as part of multimodal therapy for interstitial cystitis / bladder pain syndrome.[1][2][3] A small uncontrolled sequential-treatment series also described imipramine for retrograde ejaculation in 33 men with diabetes (antegrade ejaculate in complete cases; semen quality in partial cases).[32] See the alpha-agonists page for regimens and limitations.[8]

For class-level pharmacology, comparative TCA selection, and imipramine's role alongside amitriptyline, nortriptyline, and doxepin, see the TCAs hub. For duloxetine's SUI evidence and safety considerations, see SNRIs. Desmopressin is an option for childhood nocturnal enuresis when rapid control is needed or an alarm is unsuitable, and for selected men with nocturnal polyuria after other causes and treatments are addressed.[22][31]

Mechanism of Action — Why Imipramine Works in the Urinary Tract​

Several mechanisms have been proposed for its urinary effects. The HCl label states that its enuresis mechanism is not established.[1]

MechanismClinical effect
Muscarinic antagonism↓ detrusor contractility, ↑ bladder capacity, ↓ uninhibited contractions[2][4]
NE + 5-HT reuptake inhibition↑ sympathetic tone at bladder neck / proximal urethra → ↑ outlet resistance; central modulation of the micturition reflex at spinal and supraspinal levels[2][3][4]
Direct detrusor smooth-muscle inhibitionInhibits bethanechol- and BaCl₂-induced contractions independent of muscarinic blockade[2]
Central arousal modulationA Cochrane review describes improved arousability as a proposed effect of tricyclics.[4] The HCl label does not establish the mechanism for childhood enuresis.[1]
Vasopressin-independent antidiuretic effectIn a single-dose physiology study of 15 enuretic patients aged 15–37 years, marked antidiuresis was observed in the six with severe nocturnal polyuria after 1 mg/kg. The authors proposed increased proximal tubular α-adrenergic stimulation, followed by increased distal urea and water reabsorption.[5]

In one retrospective series, most children who had failed desmopressin, an alarm and an anticholinergic still responded to imipramine.[8]

Formulations and Dosing​

FormulationStrengthsTypical urologic dosing
Imipramine HCl tablets10, 25, 50 mgEnuresis: 25–75 mg QHS (see below); historical adult studies used varying doses, not a routine OAB regimen[1][11]
Imipramine pamoate capsules75, 100, 125, 150 mgDepression formulation; not approved for pediatric use and not a substitute for the HCl tablet enuresis regimen[25]

Enuresis (only FDA-approved urologic indication)[1]​

  • The label requires organic causes to be excluded first, with VCUG and cystoscopy "as necessary" when daytime frequency or urgency is present; uncomplicated monosymptomatic bedwetting does not need them. Refer atypical or refractory cases.[1][22]
  • Children ≥6 years: start 25 mg 1 hour before bedtime; the HCl label permits 50 mg nightly in children under 12 if inadequate after 1 week.[1]
  • Children over 12: the label permits up to 75 mg nightly; follow the exact product or local pediatric protocol at age boundaries.[1]
  • Maximum: 75 mg/day in children; do not exceed 2.5 mg/kg/day.[1]
  • A dose above 75 mg/day does not improve efficacy and tends to increase side effects.[1] For early-night wetters the label suggests 25 mg in mid-afternoon, repeated at bedtime.[1]
  • Effectiveness may decrease with continued use; relapse on discontinuation is common (NICE: more than two in three children relapse after a 3-month course). Taper rather than stop abruptly, and consider a drug-free period after a good response. NICE advises a 3-month initial course and medical review every 3 months during repeated courses.[1][22]

Off-label adult voiding indications​

  • OAB / detrusor overactivity: titrated up to 150 mg QHS (or until continent or side effects) in the Castleden 1981 case series of 10 elderly patients[11]. There is no guideline-endorsed OAB dose. The label's antidepressant geriatric dosing starts at 30–40 mg/day and generally does not exceed 100 mg/day.[1]
  • SUI: 75 mg/day (dose used in the Gilja 1984 open-label series)[14]; but see the Kornholt 2019 negative RCT below before prescribing.[15]

Imipramine has a narrow therapeutic index, and overdose can be fatal.[1] The label states that children are more sensitive than adults and that an acute overdose of any amount in an infant or young child must be considered serious and potentially fatal; toxicity (dysrhythmia, hypotension, convulsions) develops rapidly and needs hospital monitoring.[1] Counsel parents about secure storage and the danger of exceeding the prescribed amount;[22] dispense limited quantities; assess cardiac history and obtain ECG monitoring according to age or risk and the specialist protocol.

Indications in Reconstructive and Functional Urology​

1. Childhood nocturnal enuresis — FDA-approved​

Specialist option after behavioral care and unsuccessful enuresis alarm and/or desmopressin treatment, with reassessment for contributing conditions; an antimuscarinic trial is not required first.[7][8]

Efficacy data:

  • Cochrane 2016 update: imipramine yields approximately 1 fewer wet night per week versus placebo (MD −0.95; 95% CI −1.40 to −0.50; 4 trials, 347 children); 78% of children fail to achieve 14 consecutive dry nights on imipramine versus 95% on placebo (RR 0.74; 95% CI 0.61–0.90; 12 trials, 831 children). The effect was not sustained: at follow-up, 96% of imipramine recipients versus 97% of placebo recipients had not achieved 14 consecutive dry nights or had relapsed (5 trials, 416 children); alarms were more effective than tricyclics. Cochrane rated both on-treatment imipramine–placebo estimates as very-low-certainty evidence and the follow-up failure-or-relapse estimate as low-certainty evidence.[4] The 12-trial complete-response comparison had substantial heterogeneity (I² = 98%); funnel-plot asymmetry suggested that the true effect may be smaller.[4] Other drug classes (for example indomethacin, diazepam, atomoxetine) have been tested in small, mostly poor-quality trials.[6]
  • Imipramine plus oxybutynin had a lower rate of failure to achieve 14 consecutive dry nights than placebo in one 47-child trial (33% versus 78%; RR 0.43, 95% CI 0.23–0.78).[4] NICE advises against combining imipramine with an anticholinergic for bedwetting in children and young people.[22]
  • Gepertz & Nevéus 2004 (retrospective; 49 therapy-resistant enuretic children, all previously treated with desmopressin, 41 with an alarm, and 45 with an anticholinergic): among 48 children whose response could be assessed, 31 had at least 50% fewer wet nights and 17 did not respond; 22 of the 31 responders became completely dry.[8]
  • Favorable predictors in the Gepertz cohort: older age, low spontaneous bladder capacity.[8]
  • Poor predictors: constipation, daytime incontinence; treat these first.[8]

ECG: the label calls for an ECG before larger-than-usual doses and at intervals thereafter, and cardiac surveillance at every dose in patients with cardiovascular disease. An AAFP review recommends screening ECG for long QT syndrome before starting imipramine; use that guidance with the label's dose- and cardiovascular-risk instructions in the specialist pediatric protocol.[1][7]

2. Overactive bladder / detrusor overactivity — off-label​

The dual action, decreased detrusor contractility plus increased outlet resistance, is theoretically attractive, but data are thin and old.

  • Castleden 1981 (n = 10 elderly patients, unstable detrusor contractions, imipramine titrated to 150 mg QHS): 6/10 became continent. In the 3 of those 6 who had repeat cystometry, mean capacity rose 105 mL, bladder pressure at capacity fell 18 cm H₂O and urethral pressure rose 30 cm H₂O. Uncontrolled and very small.[11]
  • Castleden 1986 (double-blind placebo comparison in elderly incontinent patients; all received habit retraining): 14/19 on imipramine versus 6/14 on placebo became dry, but the between-group difference was not statistically significant.[30]
  • The AHCPR guideline cautioned that TCAs be reserved for carefully evaluated patients given the side-effect profile.[12] The Cochrane review's sole imipramine comparison was a short-term crossover study in 15 women with detrusor instability (10 in the imipramine–emepronium comparison). A single 50 mg intramuscular imipramine dose did not show a clinically significant cystometric improvement at 10 or 30 minutes, whereas emepronium did; oral therapy and continence outcomes were not tested.[13] Reviews described imipramine as possibly useful, alone or with an antimuscarinic; a 2011 review said its use had not yet been adequately assessed, and a 2000 review said its mechanism in OAB was unresolved.[9][10]
  • Guideline position: the AUA/SUFU 2024 idiopathic OAB guideline does not list tricyclics among its pharmacologic options,[23] and NICE NG123 advises not offering imipramine to women for urinary incontinence or OAB.[24] Antimuscarinics, β₃-agonists and onabotulinumtoxinA have displaced it from routine use.[23]

3. Stress urinary incontinence — off-label, clinical efficacy unestablished​

  • Gilja 1984. After 75 mg/day for 4 weeks in an uncontrolled study, 21 of 30 women stated they were continent; nine reported no improvement. Functional urethral length increased, but the study did not test clinical benefit against a comparator.[14]
  • Kornholt 2019 (double-blind, placebo-controlled, crossover RCT in 16 healthy women, single 50 mg dose): compared with placebo, urethral opening pressure was 6.5 cm H₂O higher at rest and 7.9 cm H₂O higher during squeeze; neither statistically significant nor clinically relevant.[15] Authors recommend against off-label use for SUI.
  • For urethral-closure-pressure augmentation, duloxetine has a better evidence base (EU-approved though not US-approved for SUI).

4. Mixed urinary incontinence — off-label, no data​

  • Norton and Brubaker described imipramine as historically recommended for mixed UI on mechanistic grounds but reported no clinical effectiveness data.[3] NICE NG123 advises against offering imipramine to women for urinary incontinence or OAB.[24]

5. Interstitial cystitis / bladder pain syndrome — other TCAs preferred​

  • For IC/BPS, amitriptyline is the TCA that guidelines name. The 2022 AUA guideline lists it as an oral option (Statement 14, Option, Evidence Strength Grade B, alongside cimetidine, hydroxyzine and pentosan polysulfate, with no hierarchy); the guideline does not mention imipramine.[16][17][18]
  • Network meta-analysis (Di 2021): amitriptyline reduced ICSI scores by MD −4.9 (95% CI −9.0 to −0.76) versus placebo.[19]
  • Historical reviews describe tricyclic antidepressants, including imipramine, for IC/BPS.[20][21] AUA 2022 lists amitriptyline as an oral option (Option, Evidence Strength Grade B) and does not list imipramine.[18]
  • See the TCAs hub for class-level IC/BPS detail and the limitations of dose-tolerant subgroup findings.

Contraindications & Precautions​

Boxed warning and contraindications[1]

  • Suicidality in children, adolescents, and young adults (antidepressant class boxed warning; the label weighs it against clinical need, and the enuresis indication is the only pediatric use it recognizes)
  • Concomitant MAOIs are contraindicated (hyperpyretic crisis, severe convulsions; potentiation can be fatal). When switching between imipramine and an MAOI used for a psychiatric disorder, allow at least 14 days in either direction.[1][25]
  • Acute recovery period after MI
  • Known hypersensitivity, including cross-sensitivity to other dibenzazepines (desipramine)

Cardiac[1]

  • QT prolongation, arrhythmias, heart block, orthostatic hypotension, tachycardia
  • The label calls for ECG assessment before larger-than-usual doses and at intervals thereafter; cardiac disease requires surveillance at any dose. Pediatric or refractory prescribing needs specialist cardiac-risk assessment
  • Use with caution in structural or conduction disease

Anticholinergic (urologic relevance)[1]

  • Urinary retention. The same mechanism that helps OAB can precipitate retention in men with BOO, patients with underactive detrusor, or those on concurrent antimuscarinics
  • Anatomically narrow angles: mydriasis can precipitate angle-closure glaucoma (the label lists a history of narrow-angle glaucoma or urinary retention under "extreme caution"; open-angle glaucoma is not a risk factor)
  • Xerostomia, constipation, blurred vision
  • Cognition and anticholinergic burden. The HCl label reports confusional states with hallucinations and disorientation, especially in older adults, and SIADH-related hyponatremia, with greater risk in older or volume-depleted patients.[1] Include imipramine in the anticholinergic tally when weighing cognitive risk.[26] AUA/SUFU advises discussing dementia and cognitive risk with OAB patients taking antimuscarinics .[23] The 2023 AGS Beers Criteria advise avoiding imipramine in adults aged 65 years or older in most circumstances because of anticholinergic, sedating, and orthostatic effects.[26]

Neurologic[1]

  • Lowers seizure threshold; caution in epilepsy
  • Sedation, tremor, dizziness

Endocrine / sexual[1]

  • SIADH, gynecomastia, decreased libido, ejaculatory dysfunction

Drug interactions[1]

  • CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) substantially raise imipramine levels
  • Methylphenidate and clonidine. Methylphenidate may inhibit imipramine metabolism and require a lower imipramine dose; imipramine may block clonidine's pharmacologic effects. The HCl label calls for extreme caution with either combination.[1]
  • MAOIs. Contraindicated
  • Desmopressin for adult nocturia. If NOCDURNA is used concurrently with imipramine, monitor serum sodium more frequently.[29]
  • Other anticholinergics. Cumulative burden; risk of paralytic ileus; the label calls for close supervision and dose adjustment
  • Sympathomimetics and CNS depressants. Potentiated
  • Alcohol. Increased sedation and lowered seizure threshold

Pregnancy and lactation[1]

  • Use only if potential benefit justifies potential fetal risk; excreted in breast milk.

Perioperative Considerations​

  • Coordinate elective-surgery management with anesthesia and the prescriber. The US HCl label advises discontinuing imipramine for as long as the clinical situation allows before elective surgery; UKCPA advises continuing it for elective and emergency surgery and informing anesthesia about arrhythmia and vasopressor risks. Reconcile these directions for the patient's indication, dose and withdrawal risk.[1][27]
  • Cardiac, vasopressor and ECG review. Imipramine can exaggerate the cardiovascular response to epinephrine, norepinephrine or phenylephrine; UKCPA advises reduced, carefully titrated vasopressor doses. The HCl label advises avoiding sympathomimetic-containing local anesthetics, while UKCPA advises monitoring when modern epinephrine-containing preparations are used.[1][27] Review cardiovascular disease, imipramine dose and QT-prolonging co-medications (for example, ondansetron, clarithromycin, ciprofloxacin and methadone) with anesthesia.[27][28] The HCl label calls for an ECG before larger-than-usual doses and at intervals thereafter, and cardiac surveillance at any dose in patients with cardiovascular disease.[1]
  • Flag urinary retention risk after any pelvic, prolapse, or sling procedure; imipramine adds anticholinergic load at the same time the bladder is recovering from surgical edema and opioid analgesia.
  • Avoid concomitant anticholinergics where possible in the perioperative window; if unavoidable, monitor for post-op ileus.
  • Review serotonergic combinations. The imipramine pamoate label warns of serotonin syndrome with linezolid, intravenous methylene blue, fentanyl, tramadol, and other serotonergic agents. If urgent linezolid or intravenous methylene blue is needed and alternatives are unavailable, the label calls for stopping imipramine promptly and monitoring for symptoms for two weeks or until 24 hours after the last dose, whichever comes first; it permits resumption 24 hours after the last dose. The risk with nonintravenous methylene blue is unclear.[25] See methylene blue for the intraoperative caveat.

Evidence Summary​

IndicationEvidence LevelKey Trial / GuidelineNotes
Childhood nocturnal enuresisLabel indication; randomized evidenceCochrane[4]; Gepertz 2004[8]; AAFP 2022[7]Specialist refractory option; gradual withdrawal and 3-monthly review
Imipramine + oxybutynin for primary monosymptomatic enuresis1bCochrane[4]One small placebo comparison; NICE advises against this combination for bedwetting[22]
OAB / detrusor overactivityHistorical case series and one small inconclusive placebo comparisonCastleden 1981[11]; Castleden 1986[30]; AUA/SUFU 2024[23]; NICE NG123[24]Castleden 1986 found no statistically significant between-group difference; not in AUA/SUFU options, and NICE advises against use in women
SUIClinical efficacy unestablishedGilja 1984[14]; Kornholt 2019[15]Gilja reported short-term self-reported continence without a control; Kornholt found no significant acute rise in urethral opening pressure in healthy women, without measuring SUI outcomes.
Mixed UINo dataNorton & Brubaker 2006[3]Treat dominant symptom with first-line therapy
IC/BPSImipramine efficacy unestablished; amitriptyline is an AUA oral Option (Grade B)Di 2021 NMA[19]; AUA 2022[18]Imipramine rarely used — see TCAs hub
Nocturnal polyuria / nocturiaMechanistic signal (six of 15 adolescent and adult enuretics with severe nocturnal polyuria, single dose)Hunsballe 1997[5]Desmopressin is the standard — imipramine is not used for isolated nocturia in adults

Practical Pearls​

  • Imipramine has an FDA-labeled childhood-enuresis indication.[1] Amitriptyline is the TCA named in the AUA IC/BPS guideline.[18]
  • Assess cardiac risk and ECG requirements before treatment and escalation; use the label and specialist pediatric protocol.
  • Dispense small quantities. The HCl label advises the smallest quantity consistent with good care because overdose can be fatal, particularly in infants and young children.[1]
  • Anticipate decreased efficacy over time for enuresis; plan for drug holidays and eventual taper rather than indefinite use.
  • Taper; do not stop abruptly. Cholinergic rebound (nausea, headache, malaise) is common.
  • Assess daytime incontinence and constipation first in children with enuresis; these predict poor imipramine response and have their own first-line therapies.
  • Kornholt's single-dose trial found no significant urethral-pressure change in healthy women, but it did not measure continence in patients with SUI.[15]
  • Screen carefully for BOO in men and for underactive detrusor in any adult before prescribing; imipramine can precipitate retention.

See Also​

References​

1. Imipramine hydrochloride tablets: US prescribing information. DailyMed label. Accessed September 12, 2026.

2. Sullivan J, Abrams P. "Pharmacological management of incontinence." Eur Urol. 1999;36(Suppl 1):89–95. doi:10.1159/000052327

3. Norton P, Brubaker L. "Urinary incontinence in women." Lancet. 2006;367(9504):57–67. doi:10.1016/S0140-6736(06)67925-7

4. Caldwell PHY, Sureshkumar P, Wong WCF. Tricyclic and related drugs for nocturnal enuresis in children. Cochrane Database Syst Rev. 2016;1:CD002117. doi:10.1002/14651858.CD002117.pub2.

5. Hunsballe JM, Rittig S, Pedersen EB, Olesen OV, Djurhuus JC. "Single dose imipramine reduces nocturnal urine output in patients with nocturnal enuresis and nocturnal polyuria." J Urol. 1997;158(3 Pt 1):830–836. doi:10.1016/S0022-5347(01)64330-1

6. Deshpande AV, Caldwell PH, Sureshkumar P. "Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics)." Cochrane Database Syst Rev. 2012;12:CD002238. doi:10.1002/14651858.CD002238.pub2

7. Lauters RA, Garcia KW, Arnold JJ. "Enuresis in children: common questions and answers." Am Fam Physician. 2022;106(5):549–556. PMID 36379501

8. Gepertz S, Nevéus T. "Imipramine for therapy resistant enuresis: a retrospective evaluation." J Urol. 2004;171(6 Pt 2):2607–2610. doi:10.1097/01.ju.0000110613.51078.93

9. Athanasopoulos A. "The pharmacotherapy of overactive bladder." Expert Opin Pharmacother. 2011;12(7):1003–1005. doi:10.1517/14656566.2011.554397

10. Andersson KE. "Treatment of overactive bladder: other drug mechanisms." Urology. 2000;55(5A Suppl):51–57. doi:10.1016/s0090-4295(99)00495-1

11. Castleden CM, George CF, Renwick AG, Asher MJ. "Imipramine — a possible alternative to current therapy for urinary incontinence in the elderly." J Urol. 1981;125(3):318–320. doi:10.1016/s0022-5347(17)55023-5

12. Wein AJ. "Pharmacologic options for the overactive bladder." Urology. 1998;51(2A Suppl):43–47. doi:10.1016/s0090-4295(98)90009-7

13. Roxburgh C, Cook J, Dublin N. "Anticholinergic drugs versus other medications for overactive bladder syndrome in adults." Cochrane Database Syst Rev. 2007;(4):CD003190. doi:10.1002/14651858.CD003190.pub4

14. Gilja I, Radej M, Kovacić M, Parazajder J. "Conservative treatment of female stress incontinence with imipramine." J Urol. 1984;132(5):909–911. doi:10.1016/s0022-5347(17)49941-1

15. Kornholt J, Sonne DP, Riis T, Sonne J, Klarskov N. "Effect of imipramine on urethral opening pressure: a randomized, double-blind, placebo-controlled crossover study in healthy women." Neurourol Urodyn. 2019;38(4):1076–1080. doi:10.1002/nau.23955

16. Buford K, Peters KM, Riedl C, et al. "Global consensus on interstitial cystitis/bladder pain syndrome: an update on therapeutic treatments." Neurourol Urodyn. 2026;45(1):46–53. doi:10.1002/nau.70106

17. Chermansky CJ, Guirguis MO. "Pharmacologic management of interstitial cystitis/bladder pain syndrome." Urol Clin North Am. 2022;49(2):273–282. doi:10.1016/j.ucl.2022.01.003

18. 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

19. Di XP, Luo DY, Jin X, et al. "Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis." Int Urogynecol J. 2021;32(5):1129–1141. doi:10.1007/s00192-020-04659-w

20. French LM, Bhambore N. "Interstitial cystitis/painful bladder syndrome." Am Fam Physician. 2011;83(10):1175–1181. PMID 21568251

21. Metts JF. "Interstitial cystitis: urgency and frequency syndrome." Am Fam Physician. 2001;64(7):1199–1206. PMID 11601802

22. NICE. Bedwetting in under 19s (CG111), recommendations 1.13–1.14. Guideline. Accessed September 12, 2026.

23. 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

24. NICE. Urinary incontinence and pelvic organ prolapse in women: management (NG123), recommendation 1.4.28. Guideline. Accessed September 24, 2026.

25. Imipramine pamoate capsules: US prescribing information. Warnings and Dosage and Administration. DailyMed label. Accessed October 3, 2026.

26. American Geriatrics Society Beers Criteria Update Expert Panel. "American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults." J Am Geriatr Soc. 2023;71(7):2052–2081. doi:10.1111/jgs.18372

27. UK Clinical Pharmacy Association. "Imipramine." Handbook of Perioperative Medicines. Guidance. Accessed October 3, 2026.

28. Methadone hydrochloride tablets: US prescribing information. Section 5.3. DailyMed label. Accessed October 3, 2026.

29. NOCDURNA (desmopressin acetate) sublingual tablets: US prescribing information. Sections 5.1 and 7.1. DailyMed label. Accessed October 3, 2026.

30. Castleden CM, Duffin HM, Gulati RS. "Double-blind study of imipramine and placebo for incontinence due to bladder instability." Age Ageing. 1986;15(5):299–303. doi:10.1093/ageing/15.5.299

31. NICE. Lower urinary tract symptoms in men: management (CG97), recommendation 1.4.10. Guideline.

32. Arafa M, El Tabie O. "Medical treatment of retrograde ejaculation in diabetic patients: a hope for spontaneous pregnancy." J Sex Med. 2008;5(1):194–198. doi:10.1111/j.1743-6109.2007.00456.x