INTRODUCTION — Urinary incontinence is common, occurring in approximately 15 percent of five-year-old children. Many of these children have isolated nocturnal enuresis (monosymptomatic nocturnal enuresis).
The management of monosymptomatic nocturnal enuresis in children will be presented here. An overview of the causes and evaluation of nocturnal enuresis and bowel and bladder dysfunction are discussed separately.
●(See "Nocturnal enuresis in children: Etiology and evaluation".)
●(See "Etiology and clinical features of bladder dysfunction in children".)
●(See "Evaluation and diagnosis of bladder dysfunction in children".)
●(See "Management of bladder dysfunction in children".)
The recommendations in this topic review are largely consistent with those of expert groups, including the International Children's Continence Society and the National Institute for Health and Care Excellence [1,2]. (See 'Society guideline links' below.)
TERMINOLOGY
Types of enuresis — The International Children's Continence Society (ICCS) has developed standardized terminology for lower urinary tract function and malfunction in children [3]. The terminology is summarized below and discussed in detail separately. (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Terminology' and "Etiology and clinical features of bladder dysfunction in children", section on 'Definitions of symptoms'.)
●Enuresis (synonymous with intermittent nocturnal incontinence) – Discrete episodes of urinary incontinence during sleep in children ≥5 years of age.
●Monosymptomatic enuresis – Enuresis in children without any other lower urinary tract symptoms (eg, increased frequency, daytime incontinence, urgency, genital or lower urinary tract pain) and without a history of bladder dysfunction.
Monosymptomatic enuresis is the focus of this topic review.
●Nonmonosymptomatic enuresis – Enuresis in children with other lower urinary tract symptoms.
Nonmonosymptomatic enuresis is discussed separately. (See "Etiology and clinical features of bladder dysfunction in children", section on 'Daytime urinary incontinence'.)
●Primary enuresis – Enuresis in children who have never achieved a satisfactory period of dryness.
●Secondary enuresis – Enuresis that develops after a dry period of at least six months; most children with secondary enuresis have no identifiable cause.
Enuresis treatment outcomes — The ICCS has also developed standardized definitions for initial and long-term enuresis treatment outcomes for research purposes; for clinical purposes, treatment success is determined by the child and family [3].
●Initial outcomes
•No response – Less than 50 percent reduction in baseline symptom frequency
•Partial response – 50 to 99 percent reduction in baseline symptom frequency
•Complete response – 100 percent reduction in baseline symptom frequency
●Long-term outcomes
•Relapse – More than one symptom recurrence per month
•Continued success – No relapse within six months after interruption of treatment
•Complete success – No relapse within two years after interruption of treatment
NATURAL HISTORY — Primary monosymptomatic nocturnal enuresis has a high rate of spontaneous resolution, with the prevalence decreasing from approximately 15 percent at age 5 years, to 5 percent at age 10 years, and to 1 to 2 percent at age ≥15 years [4,5]. (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Epidemiology and natural history'.)
PRETREATMENT EVALUATION — The pretreatment evaluation should include assessment for causes of nocturnal enuresis that may require additional evaluation and/or treatment (eg, diabetes mellitus, obstructive sleep apnea, constipation, bladder dysfunction). The etiology of enuresis and evaluation of children with enuresis are discussed separately. (See "Nocturnal enuresis in children: Etiology and evaluation".)
It is difficult to successfully treat enuresis if coexistent constipation is not addressed. When evaluating for constipation, it may be helpful to ask about soiling in addition to the usual questions about bowel habits. (See "Functional fecal incontinence in infants and children: Definition, clinical manifestations, and evaluation".)
WHEN TO INITIATE MANAGEMENT — The timing of initiation of treatment for monosymptomatic nocturnal enuresis varies from child to child. The major determinants are whether the child and caregivers view the enuresis as a problem and how strongly motivated they are to participate in a treatment program.
The age at which enuresis is considered to be a "problem" varies from family to family. If the caregivers wet the bed until late childhood, they may not be concerned about their seven year old who wets the bed. Caregivers of a four-year-old who wets the bed may be concerned if their three-year old sibling is already dry. Nocturnal enuresis usually becomes a problem for children when it interferes with their ability to socialize with peers [6]. For children who have undergone puberty, we offer treatment advice and/or interventions whether or not they or their caregivers have endorsed enuresis as a problem after we have excluded secondary causes of enuresis (eg, constipation, diabetes).
It is important to determine whether the child is mature enough to assume responsibility for treatment. Treatment probably should be delayed if it seems that the caregivers are more interested in treatment than the child and the child is unwilling or unable to assume some responsibility for the treatment program. The child must be highly motivated to participate in a treatment program that may take months to achieve successful results. (See 'Motivational therapy for select patients' below.)
Children younger than six years usually can be managed with education and motivational therapy [1]. However, age should not be the only criterion for initiation of active treatment [2]. Enuresis as infrequent as once per month is associated with decreased self-esteem and treatment can improve self-esteem, even if treatment is not completely successful [7-9]. (See 'Addition of active therapy' below.)
INDICATIONS FOR REFERRAL — Monosymptomatic nocturnal enuresis usually can be managed by the primary care provider. Indications for referral to a health care professional who specializes in the management of recurrent or refractory enuresis (eg, developmental-behavioral pediatrician, behavioral psychologist, child psychiatrist, pediatric urologist) include [1,2]:
●Suspicion of structural or anatomic abnormalities (refer to pediatric urologist).
●Nonmonosymptomatic enuresis.
●Developmental, attentional, or learning difficulties.
●Behavioral or emotional problems.
●Known or suspected physical or neurologic problems.
●Caregivers who have difficulty coping with bedwetting or express anger, negativity, or blame toward the child; these caregivers may need additional support [2]. The possibility that the child is being abused should be considered if the caregivers report that the child is deliberately wetting the bed.
●Refractory enuresis. (See 'Refractory enuresis' below.)
INITIAL MANAGEMENT — When the caregivers and child are interested and motivated to work toward long-term management, initial management of enuresis involves treatment of coexisting conditions, clarification of goals and expectations, provision of education/advice, and motivational therapy (table 1).
Treatment of coexisting conditions — Treatment of coexisting conditions should occur simultaneously with treatment of enuresis [1,2]. Coexisting conditions may affect prognosis and/or the response to treatment. Underlying stressors that are identified in children with secondary enuresis should be addressed.
The treatment of conditions that commonly occur in children with primary nocturnal enuresis is discussed separately:
●Constipation (see "Chronic functional constipation and fecal incontinence in infants, children, and adolescents: Treatment", section on 'Treatment of constipation in children')
●Sleep disordered breathing (see "Management of obstructive sleep apnea in children")
●Attention deficit hyperactivity disorder (see "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis")
Establish goals and expectations — The goals of management of nocturnal enuresis include [10,11]:
●Staying dry on particular occasions (eg, sleepover)
●Reducing the number of wet nights
●Reducing the impact of enuresis on the child and family
●Avoiding recurrence
Before beginning therapy, the clinician should determine patient and family priorities (eg, short-term dryness to attend camp, quality of life), which may affect the treatment strategy. (See 'Selecting active therapy' below.)
The clinician should also define the caregivers' and child's expectations. Some caregivers may simply want assurance that the enuresis is not caused by a physical abnormality and are not interested in initiating a long-term treatment program. The clinician should stress to the caregivers and child that enuresis management often involves several methods of treatment, used in sequence or combination. The treatment may be prolonged, may fail in the short term, and often is associated with relapses. The caregivers must be willing to participate, and the family environment must be supportive. Therapy should be goal oriented, and follow-up should be consistent [12].
Education and advice — Education and advice for the initial management of enuresis includes the following points [1,2,13-15]:
●Enuresis is common; it occurs at least once per week in approximately 15 percent of five year olds; enuresis resolves on its own in the majority of children (figure 1). (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Epidemiology and natural history'.)
●Neither the child nor the caregivers are at fault for enuresis; children should not be punished for bedwetting [1,2,13]. (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Pathogenesis'.)
This point deserves special emphasis. Surveys indicate that between one-fourth and one-third of caregivers punish their child for wetting the bed, and sometimes the punishment is physically abusive [6,16,17]. (See 'Indications for referral' above.)
In a small randomized trial, a psychological intervention for caregivers of children with nocturnal enuresis focused on strategies to improve understanding of enuresis, reduce conflicts, and improve family cooperation with treatment was associated with improved caregiver coping, improved tolerance, reduced punishment, increased dry nights, and greater rates of complete response [18].
●The impact of bedwetting can be reduced by:
•Using bed protection and washable/disposable products
•Using room deodorizers
•Thoroughly washing the child before dressing
•Using emollients to prevent chafing
●Keeping a calendar of wet and dry nights helps to determine the effect of interventions (form 1). (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Voiding diary'.)
●The child should attempt to void a total of four to seven times per day, including just before going to bed; if the child wakes at night, the caregivers should take the child to the toilet.
●High-sugar and caffeine-based drinks should be avoided in children with enuresis, particularly in the evening hours.
●Restricting fluid intake in the evening may be helpful for some children but should be continued only if it is successful [1]. Some experts counsel their patients with enuresis to drink 40 percent their total daily fluid in the morning (7 AM to 12 PM), 40 percent in the afternoon (12 PM to 5 PM), and only 20 percent in the evening (after 5 PM) [6]. Consuming greater proportions of total daily fluid in the morning and afternoon reduces the need for intake later in the day. Simply restricting fluid intake in the evening, without compensatory increase early in the day, may prevent the child from meeting their daily fluid requirement and is usually unsuccessful. (See "Maintenance intravenous fluid therapy in children", section on 'Components of maintenance fluid therapy'.)
●The routine use of diapers and pull-ups can interfere with motivation for getting up at night and is generally discouraged (exceptions can be made when the child is sleeping away from home) [11].
Motivational therapy for select patients — Motivational therapy is an appropriate initial therapy for nocturnal enuresis in children between five and seven years of age who do not wet the bed every night [2,12,19]. Those who have agreed to take some responsibility for their treatment can be motivated by keeping a record of progress. Initial rewards should be given for agreed-upon behavior (eg, going to the toilet before bedtime) rather than dryness [2]. Successively larger rewards, agreed upon in advance, are given for longer adherence to agreed-upon behavior and, eventually, for longer periods of dryness (eg, a sticker on a calendar for each dry night, a book for seven consecutive dry nights). Penalties (eg, removal of previously gained rewards) are counterproductive [20].
In a systematic review of comparative clinical trials of simple behavioral interventions for nocturnal enuresis, reward systems (eg, star charts) were associated with fewer wet nights per week (mean difference -4.6, 95% CI -6.4 to -2.9) and greater achievement of 14 consecutive dry nights (32 versus 19 percent) than no treatment or control interventions, but these findings were based on one or two small trials with heterogeneous rewards [19].
ADDITION OF ACTIVE THERAPY — Initial active therapies include enuresis alarms and desmopressin (a synthetic vasopressin analog) [1,21-23].
Indications — We suggest active therapy to children with monosymptomatic nocturnal enuresis who have no improvement after three to six months of initial management if enuresis continues to be a problem for the child and family (eg, is associated with diminished self-esteem, prevents the child from attending sleepovers). Although primary monosymptomatic enuresis has a high-rate of spontaneous resolution, active therapy may hasten improvement, improve self-esteem, and permit overnight activities.
Selecting active therapy
Suggested approach — For families who agree to add active therapy, we suggest an enuresis alarm or desmopressin rather than combination alarm and desmopressin therapy or other medications (eg, anticholinergic agents, tricyclic antidepressants) as the initial active therapy for children with monosymptomatic nocturnal enuresis. Alarms and desmopressin are effective, simpler than combination therapy, and have few serious adverse effects [21,23,24].
The choice between an alarm and desmopressin depends upon family preference, taking into consideration how soon a response is desired, the motivation and commitment of the child and family, and the frequency and volume of enuresis [1]. (See 'Comparison of alarms and desmopressin' below.)
●For children who have enuresis more than twice per week and in whom short-term improvement is not a priority (eg, the family is not having difficulty coping with the burden of bedwetting and is not expressing anger, negativity, or blame toward the child), we suggest an enuresis alarm. (See 'Using an enuresis alarm' below.)
Enuresis alarms have lower relapse rates but require a highly motivated child and family and a time commitment of at least three months [25,26]. Adherence is challenging, particularly if enuresis occurs more than once per night.
●For children in whom short-term improvement is a priority (eg, desire to attend overnight camp; caregivers who have difficulty coping with the burden of bedwetting or are expressing anger, negativity, or blame toward the child), who have nocturnal polyuria with normal daytime voided volumes (ie, maximum voided volume approximates expected bladder capacity), or who have enuresis ≤2 times per week, we suggest desmopressin. (See 'Using desmopressin' below.)
Nocturnal polyuria is defined by nocturnal urine production greater than 130 percent of expected bladder capacity for age [1]. By convention, estimated expected bladder capacity (in mL) equals 30 x (age [in years] +1) [3]; this formula is valid until adult bladder capacity (approximately 400 mL) is achieved [1].
Desmopressin is more rapidly effective than alarms and requires a shorter time commitment and less caregiver supervision, but has a higher relapse rate [1,14,24]. Because it decreases nocturnal urine production, desmopressin works best for children with nocturnal polyuria and normal bladder capacity [1,14,27,28].
Desmopressin should not be used in children with hyponatremia or a history of hyponatremia [29].
Comparison of alarms and desmopressin
●Effectiveness – Alarms and desmopressin are both effective in reducing nocturnal enuresis [1,21-23].
•Alarm versus desmopressin – In a meta-analysis of randomized trials comparing alarms and desmopressin, they appeared to be similarly effective in reducing the number of wet nights (mean difference [MD] of 0.6 fewer wet nights with alarms than with desmopressin [95% CI 1.8 fewer to 0.5 more wet nights with alarms than with desmopressin]; three trials including 285 children) and achieving 14 consecutive nights of dryness (47 percent with alarms, 40 percent with desmopressin; risk ratio [RR] 1.1, 95% CI 0.9-1.4; 12 trials including 1168 children) [23]. These findings are limited by inclusion of patients with nonmonosymptomatic nocturnal enuresis, lack of concealment, high attrition, publication bias, and poorly defined treatment outcomes. (See 'Enuresis treatment outcomes' above.)
In a separate network meta-analyses of randomized trials of interventions for children with monosymptomatic nocturnal enuresis, the risk of relapse was lower with alarms than with desmopressin (odds ratio [OR] 0.15, 95% CI 0.03-0.53) [24]. Relapse was defined by >1 wet night per week for children with complete response or >50 percent of pretreatment wetting frequency for those with partial response.
•Alarm versus control – In meta-analyses of randomized controlled trials comparing enuresis alarms with nonfunctioning alarms or no treatment, children in the alarm group had fewer wet nights per week (MD -2.7, 95% CI -5.0 to -0.8; four trials including 127 children), and more children in the alarm group were dry for ≥14 consecutive nights during (65 versus 13 percent; RR 7.2, 95% CI 1.4-37.3; 18 trials including 827 children) and after treatment (43 versus 2 percent; RR 9.7, 95% CI 4.7-19.8; 10 trials including 366 children) [23]. These findings are limited by lack of concealment, high attrition, publication bias, and poorly defined treatment outcomes.
•Desmopressin versus placebo – In meta-analyses of randomized controlled trials comparing intranasal desmopressin (20 mcg) with placebo, children in the desmopressin group had fewer wet nights per week (MD -1.3, 95% CI -1.1 to -1.6; 12 trials including 813 children), and more children in the desmopressin group became dry for 14 consecutive nights (19 versus 2 percent; five trials including 288 children), although treatment effects were not sustained after discontinuation [21]. The intranasal formulation is no longer labeled for the treatment of enuresis because it was associated with increased risk of hyponatremic seizures [29].
●Burdens and harms
•Enuresis alarms – Enuresis alarms are not immediately effective, require substantial caregiver supervision, and require a long-term commitment (usually three to four months) [30]. (See 'Using an enuresis alarm' below.)
Serious adverse effects of enuresis alarms are uncommon [22-24,31]. Adverse effects reported in randomized trials include alarm failure, false alarms, failure to wake the child, disruption of other family members, and lack of adherence because of difficulty using the alarm [23]. Approximately 30 percent of patients discontinue enuresis alarms for various reasons, including skin irritation, disturbance of other family members, and/or failure to wake the child [11,32,33].
•Desmopressin – Adverse effects of desmopressin therapy are uncommon [1,24]. The most serious adverse effect is dilutional hyponatremia, which occurs when excess fluids are taken in the evening hours [34-36]. (See 'Administration' below.)
Using an enuresis alarm — Enuresis alarms work through conditioning: The child learns to wake or inhibit bladder contraction in response to the physiologic conditions present before wetting.
Types of alarms — Enuresis alarms consist of a sensor and an arousal device. The sensor is placed in the undergarments or on a bed pad and is activated by moisture. The arousal device is usually an auditory alarm and/or a vibrating belt or pager (figure 2 and table 2) [6,12]. The type of alarm for a particular child should be tailored to the child's needs and abilities.
Although typically used in children ≥6 years of age, alarms may be used in younger children if they are motivated, understand how the alarm works, and are able to wake to sound or touch/vibration. It is prudent to make sure that the child can wake to sound or touch/vibration before the alarm is prescribed or purchased [11].
Instructions — The alarm should be demonstrated to the child and family before use [1]. It must be used every night. The family and child should be instructed that the child is in charge of the alarm [37]. Each night before they go to sleep, the child should test the alarm; with the sound (or vibration) in mind, the child should imagine in detail, for one to two minutes, the sequence of events that occur when the alarm sounds (or vibrates) during sleep. The sequence is as follows [2,37]:
●The child turns off the alarm, gets up, and finishes voiding in the toilet (only the child should turn off the alarm). The child's being fully awake and cognizant of what is happening is critical to the success of alarm therapy. However, at the initiation of alarm therapy, it may be necessary for the caregivers to wake the child when the alarm sounds.
●The child returns to the bedroom.
●The child changes the bedding (with caregiver supervision) and clothing. Changes of bedding and clothing should be kept near the bed.
●The child wipes down the sensor with a wet cloth and then a dry cloth (or replaces the sensor if it is disposable).
●The child resets the alarm and returns to sleep.
A diary should be kept of wet and dry nights. Positive reinforcement should be provided for successful completion of the above sequence of events, waking and getting out bed to void, and for dry nights [20,38]. Penalties (eg, the removal of a reward) for wetting episodes appear to be counterproductive [20]. (See 'Motivational therapy for select patients' above.)
Monitoring response — The child should be seen in follow-up (or have video or telephone follow-up) within one to two weeks of initiating alarm therapy [1,2,11]. Subsequent management depends upon the initial response:
●Early signs of response – Treatment should be continued for at least three months if the child demonstrates early signs of response (eg, smaller wet patches, waking to the alarm, alarm going off later in the night, fewer alarms per night, fewer wet nights).
Alarm treatment should be continued until the child has had at least 14 consecutive dry nights [2,39]. This usually takes between 12 and 16 weeks, with a range of 5 to 24 weeks [39].
After a three month trial, alarm therapy should be continued if the child has more dry nights per week than at baseline, even if they have not achieved ≥14 consecutive dry nights [2]. Alternative interventions may be warranted if there has been no improvement after three months of alarm therapy. (See 'Refractory enuresis' below.)
Therapy with the alarm can be reinitiated for relapse (≥2 wet nights per month). Children who reinitiate alarm therapy usually can achieve a rapid secondary response because of preconditioning during the initial treatment program. (See 'Treatment of relapse' below.)
●Lack of early response – For children who fail to demonstrate early signs of response (eg, smaller wet patches, waking to the alarm, alarm going off later in the night, fewer alarms per night, fewer wet nights), we suggest either the addition of low dose desmopressin in addition to alarm therapy or discontinuation of the enuresis alarm with a plan for a subsequent trial in 6 to 12 months when the child is more mature.
Using desmopressin
Administration — Desmopressin is administered orally 60 minutes before bedtime [1]. The dose is titrated to best effect; at the correct dose, the antienuretic effect is immediate. The initial dose and titration vary with the formulation:
●Regular tablets (the only formulation available in the United States; nasal spray is no longer available) – The initial dose is 0.2 mg; if necessary, it can be increased to 0.4 mg after seven days. The tablets can be crushed and mixed with a small amount of soft food (eg, applesauce, yogurt) or chewed.
●Oral melt tablets – The initial dose is 120 mcg; if necessary, it can be increased to 240 mcg after seven days.
A "trial run" of desmopressin is recommended if the child plans to use it for overnight camp. The trial should take place at least six weeks before camp to adequately titrate the dose and make sure that it will be effective.
●Prevention of dilutional hyponatremia – To prevent dilutional hyponatremia during desmopressin therapy [1,21,29]:
•The oral formulation of desmopressin should be used (the intranasal formulation is not indicated for enuresis because it was associated with increased risk of hyponatremic seizures).
•Fluid intake should be limited to 6.75 ounces (200 mL) from one hour before to eight hours after administration.
•Desmopressin should be temporarily discontinued during episodes of fluid and/or electrolyte imbalance (eg, fever, recurrent vomiting or diarrhea, vigorous exercise, or conditions associated with increased water consumption).
It is not necessary to routinely measure weight, serum electrolytes, blood pressure, or urine osmolality in children being treated with desmopressin for enuresis [2].
Assessing response — The response to desmopressin should be assessed within one to two weeks [1]. Treatment should be continued for three months if there are signs of a response (eg, smaller wet patches, fewer wetting episodes per night, fewer wet nights) [2]. If enuresis improves or remits with desmopressin, the family and child can determine whether to use desmopressin every night or just for special occasions (eg, sleepovers). When it is administered daily, desmopressin should be withheld for one week every three months to determine whether continued use is necessary [1,2].
Lack of response to desmopressin within one to two weeks may be due to reduced nocturnal bladder capacity (the most common reason for unresponsiveness) or persistent nocturnal polyuria (related to increased fluid intake in the evening, increased nocturnal solute excretion, or reduced pharmacodynamic effect of desmopressin) [8,27,40].
For children who do not respond to initial treatment, the authors of this topic review offer a trial of alarm therapy followed by a trial of combination desmopressin and alarm therapy if alarm therapy is unsuccessful. Depending upon patient and caregiver preference, discontinuing alarm therapy with a plan for a subsequent trial in 6 to 12 months is an alternative to combination therapy if alarm therapy is unsuccessful.
Discontinuation — When discontinuing daily desmopressin, we suggest that the dose be tapered (eg, providing one-half the effective dose daily for two weeks before discontinuation) rather than discontinued abruptly or extending the interval between doses.
Tapering the dose may decrease the rate of relapse [41,42]. In a meta-analysis of four randomized trials including 500 children who responded to desmopressin, the rate of sustained response was greater with tapered than abrupt discontinuation (57 versus 42 percent; pooled RR 1.4, 95% CI 1.2-1.6) [42]. In subgroup analysis, decreasing the dose prevented relapse, but increasing the interval between doses did not.
TREATMENT OF RELAPSE — Relapse following initial success is defined by >1 symptom recurrence per month [3]. (See 'Terminology' above.)
For children who relapse after initial success, the authors of this topic review reinitiate the intervention that was effective for initial management [2,11]. For children who relapse after an initial course of desmopressin, tapering desmopressin over two weeks before discontinuation may prevent relapse with subsequent courses. (See 'Discontinuation' above.)
For children with multiple relapses following successful treatment with desmopressin or with an alarm, combination alarm and desmopressin therapy may be beneficial. In meta-analyses of randomized trials comparing combination alarm and desmopressin with desmopressin alone, children in the combination group had fewer wet nights per week (mean difference -0.9, 95% CI -0.4 to -1.4), and more children in the combination group achieved ≥14 consecutive dry nights during treatment (54 versus 42 percent) and after treatment (32 versus 14 percent) [23]. Similarly, in a network meta-analysis, success rates (with success defined by a ≥50 percent decrease in monosymptomatic enuresis) were greater for combination therapy than for alarm alone (odds ratio 1.9, 95% CI 1.1-3.4) [24].
REFRACTORY ENURESIS
Etiology and evaluation — Lack of response to active intervention is defined by <50 percent improvement in baseline frequency of enuresis [3].
Referral to a specialist is warranted when children do not respond to an adequate trial of treatment with an enuresis alarm (ie, three months), desmopressin (at a dose of 0.4 mg for regular tablets or 240 mcg for oral melt tablets), or a combination of alarm and desmopressin [1,2]. (See 'Indications for referral' above.)
Possible reasons for lack of response include [1,43]:
●Overactive bladder (see "Etiology and clinical features of bladder dysfunction in children", section on 'Overactive bladder')
●Underlying disease (eg, diabetes mellitus)
●Incorrect or inconsistent use of alarm (see 'Using an enuresis alarm' above)
●Occult constipation (it may be helpful to ask about soiling in addition to the usual questions about bowel habits)
●Sleep apnea (see "Evaluation of suspected obstructive sleep apnea in children", section on 'Diagnosis')
●Social and emotional factors
Additional evaluation for children with refractory enuresis may include [1]:
●Abdominal/pelvic ultrasonography (increased bladder wall thickness may indicate bladder overactivity; rectal distension may be a sign of occult constipation) (see "Evaluation and diagnosis of bladder dysfunction in children", section on 'Ultrasonography')
●Completion of a frequency volume chart if one was not completed previously
●Evaluation for occult constipation with abdominal radiographs or a trial of treatment for presumed constipation; rectal examination or anorectal manometry are rarely used to evaluate occult constipation [44,45]
Management — Refractory enuresis is generally managed in consultation with a specialist (eg, developmental-behavioral pediatrician, behavioral psychologist, child psychiatrist, pediatric urologist). (See 'Indications for referral' above.)
Following evaluation to exclude other causes of enuresis, management of refractory monosymptomatic nocturnal enuresis may include [1,2,46-48]:
●Periodic new trials of the enuresis alarm (with or without the addition of desmopressin). (See 'Using an enuresis alarm' above.)
●Desmopressin alone if continued use of an alarm is no longer acceptable to the child or caregivers or if there was a partial response to combination treatment with desmopressin and an alarm after initial treatment with an alarm. (See 'Using desmopressin' above.)
●A trial of desmopressin in combination with an anticholinergic agent.
Limited evidence from a small randomized trial suggests that the addition of an anticholinergic agent to desmopressin may be more effective than desmopressin alone [49].
●A trial of tricyclic antidepressants – Given concerns about potential toxicity, tricyclic antidepressants (TCAs) usually are tried only after other interventions have been unsuccessful [1,50]. When used to treat enuresis, TCAs usually are prescribed by a specialist (eg, developmental-behavioral pediatrician, child psychiatrist, pediatric urologist) [1]. (See 'Indications for referral' above.)
TCAs stimulate vasopressin secretion and relax the detrusor muscle. Imipramine is the TCA that is most often used in the treatment of enuresis, although other TCAs are effective [1,2,51]. In a meta-analysis of randomized trials comparing imipramine with placebo, imipramine reduced the number of wet nights per week (mean difference -1.0, 95% CI -1.4 to -0.5) and more children in the imipramine group had ≥14 consecutive dry nights (22 versus 5 percent), with similar rates of relapse (>95 percent) [51].
•Pretreatment evaluation – The pretreatment evaluation for TCA in children, which includes a thorough cardiac review of systems, is discussed separately. (See "Pediatric unipolar depression and pharmacotherapy: General principles", section on 'Pretreatment evaluation'.)
•Titration – Imipramine is administered orally one hour before bedtime. The initial dose is 10 to 25 mg; it may be increased by 25 mg if there is no response after one week (maximum dose 50 mg for children 6 to 12 years of age; maximum dose 75 mg for children ≥12 years of age) [11]. The average effective dose is 25 mg for children 5 to 8 years of age and 50 mg for older children.
A "trial run" of imipramine is recommended if the child plans to use it for overnight camp. The trial should take place at least six weeks before camp to titrate the dose adequately and make sure that it will be effective.
•Monitoring response and follow-up – The response to imipramine should be assessed after one month.
If imipramine therapy is successful, the family should taper to the lowest effective dose. Approximately every three months, imipramine should be discontinued for at least two weeks to decrease the risk of tolerance [52].
If there is no improvement after three months, imipramine should be gradually discontinued [2].
•Adverse effects – Adverse effects of TCA therapy are relatively uncommon but may be serious. Approximately 5 percent of children treated with TCAs develop neurologic symptoms, including nervousness, personality change, and disordered sleep. Imipramine, amitriptyline, and other TCAs are required by the US Food and Drug Administration (FDA) to carry a boxed warning regarding the possibility of increased suicidality, particularly in individuals with preexisting depressive symptoms. (See "Effect of antidepressants on suicide risk in children and adolescents", section on 'FDA black box warning'.)
The most serious adverse effects of TCAs involve the cardiovascular system: cardiac conduction disturbances and myocardial depression, particularly in cases of overdose [39]. (See "Tricyclic antidepressant poisoning", section on 'Clinical features'.)
OTHER INTERVENTIONS — A number of other interventions have been used for nocturnal enuresis or refractory nocturnal enuresis, including:
●Waking the child to urinate – We do not suggest that the caregivers wake the child to use the bathroom after they have fallen asleep.
Although waking the child to urinate may be more effective than no treatment and may be used as a practical measure (eg, to reduce clean-up) for children who wet the bed only once per night and have motivated caregivers, it does not condition the child to wake to the sensation of a full bladder [1,2,19,25,26,53].
●Bladder training – Bladder training, also known as retention control training, involves asking the child to hold their urine for successively longer intervals to increase bladder capacity. Although bladder training is a common component of multimodal therapy programs, we do not recommend it in the initial management of monosymptomatic nocturnal enuresis.
In randomized trials, bladder training exercises increased bladder capacity [54,55]. However, increased bladder capacity was not associated with improved enuresis or improved response rate to subsequent treatment with an enuresis alarm [54,55]. A systematic review of simple behavioral and physical interventions for nocturnal enuresis in children found insufficient evidence to evaluate bladder training in isolation or in combination with other interventions [19].
●Anticholinergic drugs – Monotherapy with anticholinergic drugs, such as oxybutynin, is not effective in treating monosymptomatic nocturnal enuresis [56,57]. However, anticholinergic agents may be useful in children with nocturnal enuresis and daytime incontinence. In such children, anticholinergic therapy may be used in combination with desmopressin to increase bladder capacity during sleep [58-62]. (See "Evaluation and diagnosis of bladder dysfunction in children", section on 'When to suspect bladder dysfunction' and "Management of bladder dysfunction in children" and "Management of bladder dysfunction in children", section on 'Pharmacologic therapy'.)
●Other drugs – Other drugs, including indomethacin, phenmetrazine, amphetamine sulfate, ephedrine, atropine, furosemide, diclofenac, and chlorprothixene have been tried in the treatment of nocturnal enuresis [63]. A 2012 systematic review of randomized trials of drugs other than tricyclic antidepressants and desmopressin found that although indomethacin, diclofenac, and diazepam were better than placebo in reducing the number of wet nights, none of the drugs was better than desmopressin [63].
●Electrical stimulation therapy – Electrical stimulation therapy, also called neuromodulation or neurostimulation, involves implantation of noninvasive devices that stimulate pelvic muscle contractions and/or modulate detrusor contractions (figure 3).
We do not routinely suggest electrical stimulation therapy for children with nocturnal enuresis. Although it has proven effective for some forms of daytime enuresis and appears to be safe and effective compared with placebo/control for nocturnal enuresis, the risk of relapse, optimal type of electrical stimulation, and effectiveness compared with other interventions for nocturnal enuresis are uncertain [64].
●Complementary and alternative therapies – A review of complementary approaches such as hypnosis, psychotherapy, and acupuncture found limited evidence from small trials with methodologic limitations to support the use of such modalities for the treatment of nocturnal enuresis [65].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Enuresis in children".)
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Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topic (see "Patient education: Bedwetting in children (The Basics)")
●Beyond the Basics topic (see "Patient education: Bedwetting in children (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Terminology and natural history – Primary monosymptomatic nocturnal enuresis (ie, bedwetting) is defined by discrete episodes of urinary incontinence during sleep in children ≥5 years of age who have never achieved a satisfactory period of nighttime dryness, have no other lower urinary tract symptoms, and have no history of bladder dysfunction. Primary monosymptomatic nocturnal enuresis has a high rate of spontaneous resolution. (See 'Terminology' above and 'Natural history' above.)
●Pretreatment evaluation – Before treatment of nocturnal enuresis, causes of nocturnal enuresis that require additional evaluation and/or treatment (eg, diabetes mellitus, obstructive sleep apnea, constipation, bladder dysfunction) should be evaluated. (See 'Pretreatment evaluation' above.)
●Initial management – Initial management of monosymptomatic nocturnal enuresis includes treatment of coexisting conditions, establishing goals and expectations, and providing of education and advice (table 1). Motivational therapy (eg, a reward system such as a star chart) may reduce the frequency of enuresis for children age five to seven years who do not wet the bed every night and have agreed to take some responsibility for management. (See 'Initial management' above.)
●Addition of active therapy – For children who continue to have problematic enuresis (eg, lessens self-esteem, prevents overnight activities) after three to six months of initial management, we suggest addition of active therapy rather than continuing initial management (Grade 2B). Although primary monosymptomatic enuresis has a high rate of spontaneous resolution, active therapy may hasten improvement, improve self-esteem, and permit overnight activities. (See 'Indications' above.)
For families who agree to add active therapy, we suggest an enuresis alarm or desmopressin rather than combination alarm and desmopressin therapy or other medications (eg, anticholinergic agents, tricyclic antidepressants) (Grade 2B). Alarms and desmopressin are effective, simpler than combination therapy, and have few serious adverse effects. (See 'Selecting active therapy' above.)
The choice between an alarm and desmopressin largely depends upon family preference, taking into consideration how soon a response is desired, the motivation and commitment of the child and family, and the frequency and volume of enuresis. (See 'Suggested approach' above and 'Comparison of alarms and desmopressin' above.)
•For children who have enuresis more than twice per week and in whom short-term improvement is not a priority (eg, the family is not having difficulty coping with the burden of bedwetting and is not expressing anger, negativity, or blame toward the child), we suggest an enuresis alarm (Grade 2B). Enuresis alarms have lower relapse rates but require a highly motivated child and family and a time commitment of at least three months. Adherence is challenging, particularly if enuresis occurs more than once per night. (See 'Using an enuresis alarm' above.)
•For children in whom short-term improvement is a priority, who have nocturnal polyuria with normal daytime voided volumes (ie, maximum voided volume approximates expected bladder capacity), or who have enuresis ≤2 times per week, we suggest desmopressin rather than an alarm (Grade 2B). Desmopressin is more rapidly effective than alarms and requires a shorter time commitment and less caregiver supervision but has a higher relapse rate. (See 'Using desmopressin' above.)
●Treatment of relapse – We treat the first relapse with the intervention(s) that were effective in the past (eg, enuresis alarm, desmopressin). For children with multiple relapses following either alarm or desmopressin therapy, combination alarm and desmopressin therapy may be beneficial. (See 'Treatment of relapse' above.)
●Refractory enuresis – When motivated children and families do not respond to an adequate trial of treatment with an enuresis alarm and/or desmopressin, referral to a health care professional who specializes in the management of bedwetting may be warranted. (See 'Refractory enuresis' above.)
