eMedicine Specialties > Pediatrics: Surgery > Urology

Enuresis: Treatment & Medication

Author: Wm Lane M Robson, MA, MD, FRCP, FRCP(Glasg), Medical Director, The Children's Clinic
Contributor Information and Disclosures

Updated: Aug 31, 2009

Treatment

Medical Care

The most important reason to treat enuresis is to minimize the embarrassment and anxiety of the child and the frustration experienced by the parents. Most children with enuresis feel very much alone with their problem. Family members with a history of enuresis should be encouraged to share their experiences and offer moral support to the child. The knowledge that another family member had and outgrew the problem can be therapeutic.

A positive attitude and motivation to be dry are important components of treatment. Children with enuresis benefit from a caring and patient attitude by their parents; punishment has no role. A positive approach by the physician is also important to instill confidence and enhance compliance. Many children have given up on the concept of dryness, and an optimistic attitude should be encouraged. Behavioral modification with positive reinforcement may enhance treatment results. Consistent follow-up is important to gauge the therapeutic results.

An explanation of the probable cause of the enuresis is important for every family. If a child has no daytime symptoms or has experienced significant dry spells in the past, the presence of a structural abnormality as a cause of the enuresis is unlikely. This should be explained to the parents to allay any fears about other causes and to reassure that invasive investigations are not necessary. Parents should be asked to provide specific examples of potential causes that have them worried, so that these often irrational fears can be discussed and relieved.

Keen attention to a normal daytime voiding pattern is important. The child should be encouraged to void upon awakening, approximately every 1.5-2 hours, before leaving home or school for any reason, and always before bed. Children should be encouraged to void regularly at school and at least twice per day at school and as necessary. A note for the teacher should be written to authorize regular access to the bathroom. Holding the urine to the last minute should be discouraged. With voiding, the child should relax, use optimal posture, and take time to completely empty the bladder.

Children should be instructed to drink liberal amounts during the day, not to drink to excess with the evening meal, and to minimize fluid intake afterward. Common-sense modifications of fluid intake are necessary to maintain hydration in children who play sports or who are otherwise physically active in the evening after mealtime. Fluid restriction should not be presented in a fashion that could be construed by the child as punishment.

Parents should be asked to take the child to the bathroom to void prior to bedtime. Because this therapeutic measure is designed only to minimize the quantity of fluid in the bladder, full wakefulness is neither necessary nor desirable. Careful monitoring by a parent is necessary for the trip from bed to bathroom and back. Children should go to bed at an hour calculated to offer the optimal hours of sleep for their age.

If attention to the above preliminary management program for up to 3 months does not result in dryness, then either alarm or pharmacologic therapy should be considered. Since no single therapy has been consistently superior, the clinical setting, family preference, and experience of the practitioner should dictate the preliminary choice.

  • Alarm therapy
    • Alarm therapy offers the possibility of sustained improvement of enuresis and should be considered for every patient. Alarm therapy is reported to improve bedwetting by increasing nocturnal bladder capacity or by enhanced arousal. Alarm therapy does not reduce nocturnal urine output. Some successfully treated children replace enuresis with nocturia, and others sleep dry without the need to void at night. Some improve within the first 2 weeks of treatment and others only after several months. The volume of enuretic urine may diminish progressively until dryness is achieved, or the improvement can be more sudden. Analysis of 25 reported studies suggests an average success rate of 68%.12
    • A number of practical considerations limit the usefulness of alarm therapy and should be discussed with the family before selecting this approach. Optimal results occur when the child is well motivated. Older children usually have better developed motivation. Parental motivation is also critical. The parent should believe the approach is worthwhile and should be prepared to participate every night for at least 3 consecutive months. The impact on other family members should be considered. If the alarm might interrupt the sleep of an infant sibling, shift-working parent, or live-in grandparent, alarm therapy may not be suitable. Numerous alarms are available. The alarm should be attached at bedtime to the underwear or pajamas in a position chosen to promptly sense wetness.
    • Although most children with enuresis do not awaken to the alarm, they stop emptying the bladder. When the alarm sounds, a parent must assist the child to the bathroom to finish voiding. After changing the sheets and underwear or pajamas, the child should be returned to bed and the alarm reset.
    • Close biweekly follow-up care is important to sustain motivation, troubleshoot technical problems, and otherwise monitor the therapy. In successfully treated children, alarm therapy should be continued for at least one month after sustained dryness. Relapses are common, develop in 29%-66% of children, and may respond to further alarm therapy. If the child is still wet after a minimum of 3 months of consecutive use, alarm therapy can be discontinued and considered unsuccessful. Failure does not preclude future successful treatment in an older, more motivated child.
  • Desmopressin acetate therapy
    • Desmopressin acetate (DDAVP) is the preferred medication to treat children with enuresis. Numerous studies report total dryness in 38%-55% of children treated with DDAVP. Although most authorities suggest the therapeutic benefit of DDAVP is due to a reduction in the nocturnal production of urine, effects on arousal may be important.
    • The tablet and oral disintegrating tablet (not available in the United States) have similar efficacy.
    • The intranasal formulation has a black box warning by the FDA and is no longer recommended for enuresis because of the risk for severe hyponatremia that can cause seizures and death.
    • DDAVP tablets or oral disintegrating tablets should be administered 1 hour before bedtime. The recommended starting dose for the tablet is 0.2 mg, and the drug can be titrated as necessary to a maximum of 0.6 mg. The equivalent starting dosage for the melt is 120 mcg and the maximum dose is 360 mcg. The immediate onset of action of DDAVP allows the flexibility of intermittent administration for special occasions or long-term use to maintain dryness. For long-term use, DDAVP can be prescribed in 3-month quantities and discontinued between prescriptions to determine if the wetting persists and, therefore, to justify continued use.
    • The safety profile of DDAVP is favorable, and many studies have documented low rates of adverse effects.
      • For the tablet, incidence of minor adverse events is not significantly different from a placebo.
      • The only serious adverse effect reported in patients with enuresis treated with desmopressin is seizure or other CNS symptoms due to water intoxication. A review of case reports of water intoxication associated with desmopressin confirmed excess fluid intake was a feature in at least 6 of 11 individuals. This serious adverse effect is preventable with careful patient education not to consume an excess of fluids on any evening that desmopressin is administered. A maximum of 1 cup of fluid should be offered at the evening meal, no more than 1 cup between mealtime and bedtime, and nothing to drink within 2 hours prior to bedtime. Early symptoms of water intoxication include headache, nausea, and vomiting. If these symptoms develop, the medication should be discontinued and the child promptly assessed by a physician.
      • As of December 2007, the US Food and Drug Administration (FDA) reviewed 61 postmarketing cases of hyponatremic-related seizures associated with the use of desmopressin. Fifty-five cases reported sodium levels ranging from 104-130 mEq/L during the seizure event. In 2 cases, the patients died (both patients experienced hyponatremia and seizures). Thirty-six cases were associated with intranasal formulations, of which 25 cases occurred in pediatric patients younger than 17 years. The most commonly reported indication of use in these 25 pediatric cases was enuresis. Thirty-nine of the 61 cases were associated with at least one concomitant drug or disease that is also associated with hyponatremia, seizures, or both.
    • Combination of alarm therapy with DDAVP is reported to result in dryness not achievable with either therapy alone.
  • Anticholinergic therapy
    • An anticholinergic medication may be helpful in some patients, especially those with overactive bladder, dysfunctional voiding, or neurogenic bladder. These medications reduce uninhibited detrusor contractions, increase the threshold volume at which an uninhibited detrusor contraction occurs, and enlarge the functional bladder capacity. Oxybutynin chloride (Ditropan) and tolterodine (Detrol) are commonly prescribed medications. Oxybutynin chloride also has antispasmodic and analgesic properties. Anticholinergic adverse effects include dry mouth, blurred vision, facial flushing, constipation, poor bladder emptying, and mood changes.
    • These medications should not be administered during a fever because a decrease in sweating is an anticholinergic effect. Similarly, these medications should be used cautiously in children who exercise or play strenuously, especially on hot days.
    • The dosage of oxybutynin is 2.5-5 mg administered at bedtime. A long-acting preparation is available but has not been approved for use in children. Tolterodine is not approved for use in children younger than 12 years. Flavoxate HCl (Urispas), a urinary spasmolytic, may be helpful in some patients with overactive bladder and dysfunctional voiding but is approved only for children older than 12 years. The combination of DDAVP and oxybutynin chloride may be efficacious in children with overactive bladder or dysfunctional voiding who respond to anticholinergic therapy with improved daytime symptoms but who continue to wet at night.
  • Imipramine therapy
    • Treatment with imipramine results in dryness in 5-40% of children. The relapse rate is high when the medication is discontinued. The usual dose, taken 1-2 hours before bedtime, is 25 mg for patients aged 6-8 years and 50-75 mg for older children and adolescents.
    • Adverse effects include constipation, difficulty initiating voiding, irritability, drowsiness, reduced appetite, and personality changes. Imipramine overdose can be fatal, and a cautionary warning is necessary with every prescription. Because of the unfavorable adverse effect profile and significant risk of death with overdose, the World Health Organization (WHO) does not recommend imipramine for the treatment of enuresis.

Surgical Care

Ectopic ureter, OSA, and heart block respond to specific surgical interventions. Enuresis is not a surgically treated condition.

Consultations

Referral to a pediatric otolaryngologist or a pediatric sleep specialist may be appropriate if OSA is suspected.

Diet

Children should be instructed to drink a liberal amount during the day but not to drink to excess with the evening meal and to minimize fluid intake after mealtime. Common-sense modifications of fluid intake are necessary to maintain hydration in children who play sports or who are otherwise physically active in the evening after mealtime.

Medication

Pharmacologic management plays an important role in the treatment of bedwetting. Three pharmacologic approaches are currently considered: desmopressin, anticholinergic medications, and imipramine.

Vasopressin Analog

Secretion of vasopressin at night reduces urine output. Water is conserved and concentrated by increasing the flow in the kidney through the collecting tubules to the medullary interstitium.

Desmopressin is a synthetic analog of ADH. The first reported use of desmopressin to treat a child with bedwetting was in the 1960s. The mechanism of action was presumed to be a reduction in the overnight production of urine. Later studies demonstrated that some children with bedwetting had lower nocturnal levels of ADH than children who were dry at night. This provided a scientific rational for desmopressin use; however, not all children with bedwetting have lower levels of ADH at night, overproduce urine at night, or respond to desmopressin. In addition, not all children who respond to desmopressin have lower levels of ADH or overproduce urine at night prior to treatment with the medication. The mechanism of action of desmopressin possibly involves factors other than control of the production of urine.

Because ADH is also a neurotransmitter, a CNS-mediated action, perhaps on arousal pathways, is speculated as a possible factor.


Desmopressin, oral (DDAVP)

Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys. Formulated as a tab and a nasal spray. Because of the risk for severe hyponatremia, the intranasal formulation is no longer indicated for PNE.

Adult

Pediatric

<6 years: Not recommended
>6 years:
Tablets: 0.2 mg PO hs initially; may titrate upward prn; not to exceed 0.6 mg PO hs
Oral disintegrating tablet (not available in United States): 120 mcg PO hs initially; may titrate upward prn; not to exceed 360 mcg (in United States, Columbia Laboratories has recently completed phase II clinical trials for buccal formulation)

Coadministration with demeclocycline and lithium decreases effects; fludrocortisone and chlorpropamide increase effects

Documented hypersensitivity; hemophilia; von Willebrand disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reduces urine production; minimize fluid intake in the evening before administration (not to exceed 8 oz with evening meal and 8 oz after evening meal; nothing 2 hours prior to bedtime); impulsive children, (eg, with ADHD) require close monitoring to minimize possibility of excess fluid intake; caution in those with coagulation disorders and predisposition to thrombus formation and in fluid and electrolyte imbalance, hypertension, or severe cardiovascular disease; may cause severe hyponatremia that can result in seizures and death; caution in patients at risk for water intoxication with hyponatremia (eg, habitual or psychogenic polydipsia, patient taking drugs that cause dry mouth or increased thirst)

Anticholinergic agents

Some children with bedwetting have a small functional bladder capacity at night. Other children with bedwetting also have daytime symptoms of frequency and urgency. These children may benefit from treatment with an anticholinergic medication that allows the bladder to hold more urine. In the absence of these situations, treatment with an anticholinergic medication is not likely to decrease the incidence of bedwetting.


Oxybutynin (Ditropan)

Should be considered in children who are likely to have small functional bladder capacity either only at night or throughout the day. Daytime symptoms that may indicate potential for therapeutic benefit include frequency, urgency, and incontinence. Nighttime symptoms include wetting more frequently than once per night. Formulated as a liquid and tab and ER form (not approved for children <12 y).

Adult

Pediatric

<12 years: Not established
>12 years:
Nighttime wetting: 0.1 mg/kg hs, not to exceed 5 mg/dose
Nighttime wetting with daytime symptoms: 0.1 mg/kg/dose PO up to tid; not to exceed 5 mg/dose

Additive effects with other anticholinergic agents

Documented hypersensitivity; not to exceed 5 mg/dose

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause anticholinergic adverse effects including dry mouth, blurred vision, constipation, flushing, and mood changes; may interfere with perspiration; caution in children with fever or who exercise or play outside, especially on hot days, because of decreased sweating


Tolterodine (Detrol)

Used in patients likely to have small functional bladder capacity either only at night or throughout the day. Daytime symptoms that may indicate potential for therapeutic benefit include frequency, urgency, and incontinence. Nighttime symptoms include wetting more frequently than once per night. Competitive muscarinic receptor antagonist for overactive bladder. Differs from other anticholinergic drugs in that it has selectivity for urinary bladder over salivary glands.

Adult

Pediatric

<12 years: Not established
>12 years: 0.5-1 mg PO qd/bid

Additive effects with other anticholinergic agents; patients treated with macrolide antibiotics or antifungal agents should not receive doses of tolterodine >1 mg bid; coadministration of CYP2D6 or CYP3A4 inhibitors may decrease clearance

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not administer doses >1 mg bid to patients with significantly reduced hepatic function; caution in renal impairment; not currently approved in the US for children <12 y


Flavoxate (Urispas)

For symptomatic relief of incontinence. Has anticholinergic effects and exerts direct effect on muscle. Counteracts smooth muscle spasm of urinary tract.

Adult

Pediatric

<12 years: Not established
>12 years: 100-200 mg PO tid/qid; reduce dose when symptoms improve

Additive anticholinergic effects may occur with coadministration of other anticholinergic agents (eg, TCAs, amantadine, phenothiazines)

Documented hypersensitivity; pyloric or duodenal obstruction; obstructive intestinal lesions; GI hemorrhage; obstructive uropathies of lower urinary tract

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause drowsiness, vertigo, and ocular disturbances; caution in glaucoma

Tricyclic antidepressants

Imipramine was first prescribed for bedwetting in an era when psychological causes were considered common. The modern understanding is that psychological causes are not a common cause of PNE. The mechanism whereby imipramine improves bedwetting is not clear. Current theories include CNS- or local bladder-related effects.


Imipramine (Tofranil)

Facilitates urine storage by decreasing bladder contractility and increasing outlet resistance. Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron.

Adult

Pediatric

6-12 years: 25-50 mg PO hs; not to exceed 50 mg/dose
>12 years: 25-50 mg PO hs; not to exceed 75 mg/dose

Increases toxicity of sympathomimetic agents (eg, isoproterenol, epinephrine) by potentiating effects and inhibiting antihypertensive effects of clonidine; may have additive CNS effects

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Has adverse effect and overdose profile that prohibits recommendation as preliminary therapy for bed-wetting; overdose can be fatal; should be prescribed with complete disclosure of potential danger and to families who will prevent access to the medication by children or emotionally disturbed individuals; no longer approved in Sweden or recommended by WHO for treatment of bed-wetting; may impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and in those receiving thyroid replacement therapy

More on Enuresis

Overview: Enuresis
Differential Diagnoses & Workup: Enuresis
Treatment & Medication: Enuresis
Follow-up: Enuresis
References
Further Reading
[ CLOSE WINDOW ]

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Keywords

enuresis, bedwetting, bed-wetting, nocturnal enuresis, NE, primary nocturnal enuresis, PNE, secondary nocturnal enuresis SNE, nocturia, voiding dysfunction, incontinence, overactive bladder, urge syndrome, dysfunctional voiding, cystitis, constipation, neurogenic bladder

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Contributor Information and Disclosures

Author

Wm Lane M Robson, MA, MD, FRCP, FRCP(Glasg), Medical Director, The Children's Clinic
Wm Lane M Robson, MA, MD, FRCP, FRCP(Glasg) is a member of the following medical societies: International Children's Continence Society, Royal College of Physicians and Surgeons of Canada, and Royal College of Physicians and Surgeons of Glasgow
Disclosure: Nothing to disclose.

Medical Editor

Howard M Snyder III, MD, Professor, Department of Surgery, Division of Pediatric Urology, University of Pennsylvania School of Medicine
Howard M Snyder III, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Urological Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond
Harry P Koo, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, and American Urological Association
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston
Marc Cendron, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, European Society for Paediatric Urology, Johns Hopkins Medical and Surgical Association, New Hampshire Medical Society, Society for Fetal Urology, and Society for Pediatric Urology
Disclosure: Nothing to disclose.

 
 
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