Disclosures: Naiwen D Tu, MD Nothing to disclose. Laurence S Baskin, MD, FAAP Nothing to disclose. Jan E Drutz, MD Nothing to disclose. Carolyn Bridgemohan, MD Equity Ownership/Stock Options: MEDCO [Autism (Prescription services)]; Merck [Autism (Vaccines)]. Mary M Torchia, MD Nothing to disclose.
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INTRODUCTION — Urinary incontinence is a common problem in children, occurring in approximately 15 percent of five-year-old children. Most 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.
TERMINOLOGY — The International Children's Continence Society has developed standardized terminology for lower urinary tract function and malfunction in children . 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 and without a history of bladder dysfunction; children who have never achieved a satisfactory period of nighttime dryness have primary enuresis; children who develop enuresis after a dry period of at least six months have secondary enuresis.
Monosymptomatic enuresis is the focus of this topic review.
Non-monosymptomatic enuresis – Enuresis in children with other lower urinary tract symptoms (eg, increased frequency, daytime incontinence, urgency, genital or lower urinary tract pain).
Non-monosymptomatic enuresis is discussed separately. (See "Etiology and clinical features of bladder dysfunction in children", section on 'Daytime urinary incontinence'.)
NATURAL HISTORY — Primary monosymptomatic nocturnal enuresis has a high rate of spontaneous resolution, with the prevalence decreasing from 16 percent at age 5 years, to 5 percent at age 10 years, and 1 to 2 percent at age ≥15 years [2,3]. (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Epidemiology and natural history'.)
PRETREATMENT EVALUATION — The evaluation of children with enuresis is discussed separately. It is particularly important to look for causes of nocturnal enuresis that may require additional evaluation and treatment (eg, diabetes mellitus, obstructive sleep apnea, encopresis or constipation, bowel and bladder dysfunction, etc). 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 "Nocturnal enuresis in children: Etiology and evaluation", section on 'Differential diagnosis' and "Sleepwalking and other parasomnias in children", section on 'Sleep enuresis' and "Evaluation of suspected obstructive sleep apnea in children".)
Overview — Guidelines for the evaluation and management of nocturnal enuresis have been developed by the International Children's Continence Society, the National Institute for Health and Care Excellence, and the Paediatric Society of New Zealand [4-6]. The recommendations in this topic review are based upon the recommendations of these groups.
Management of primary nocturnal enuresis may involve one or a combination of interventions, including:
●Education and reassurance (given the high rate of spontaneous resolution)
●Motivational therapy (eg, sticker or star chart)
The management of secondary nocturnal enuresis involves addressing the underlying stressor if one can be identified. However, most children with secondary enuresis have no identifiable cause and are treated in the same manner as children with primary enuresis.
When the parents and child are interested and motivated to work toward long-term management, education and motivational therapies usually are tried initially (for three to six months). More active intervention (eg, enuresis alarm, desmopressin) is warranted as the child gets older, social pressures increase, and self-esteem is affected. Enuresis alarms are the most effective long-term therapy, but desmopressin is effective in the short-term (eg, for sleepovers or camp attendance).
Goals of treatment — The goals of interventions for nocturnal enuresis include [7,8]:
●To stay dry on particular occasions (eg, sleepover)
●To reduce the number of wet nights
●To reduce the impact of enuresis on the child and family
●To avoid recurrence
General principles — Before beginning therapy, the pediatric healthcare provider should define the expectations of the parents and child. Some parents 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. It is also important to determine whether short-term dryness is a priority (eg, so the child can attend camp or go on a school trip) .
Pediatric healthcare providers should emphasize that bedwetting is not the child's fault and that the child should not be punished for bedwetting [4-6]. Surveys indicate that between one-fourth and one-third of parents punish their child for wetting the bed, and sometimes the punishment is physically abusive [9-11]. The possibility that the child is being abused should be considered if the parents report that the child is deliberately wetting the bed . Parents or caregivers who are having difficulty coping with bedwetting or are expressing anger, negativity, or blame toward the child may need additional support .
The pediatric healthcare provider should stress to the parents and child that a carefully constructed enuresis treatment program 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 parents must be willing to participate, and the family environment must be supportive. Therapy should be goal oriented, and follow-up should be consistent .
Comorbid constipation should be addressed in conjunction with nocturnal enuresis . (See "Prevention and treatment of acute constipation in infants and children", section on 'Acute constipation' and "Chronic functional constipation and fecal incontinence in infants and children: Treatment", section on 'Treatment of children'.)
When to initiate — 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 depending upon the family. If both parents wet the bed until late childhood, they may not be concerned that their seven-year-old wets the bed. In contrast, parents may be concerned about a four-year-old who wets if he has a three-year-old sibling who is already dry. For the child, nocturnal enuresis usually becomes significant when it interferes with his or her ability to socialize with peers . We offer treatment advice and/or interventions to children with enuresis who have undergone puberty if neither they nor their parents have endorsed enuresis as a problem before then and secondary causes of enuresis (eg, constipation, diabetes) have been excluded.
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 parents 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' below.)
Children younger than seven years usually can be managed with education and motivational therapy . However, age should not be the only criterion for initiation of active treatment . Enuresis as infrequent as once per month is associated with decreased self-esteem; decreased self-esteem can be improved with treatment, even if the treatment is not completely successful [13-15].
Indications for referral — Monosymptomatic nocturnal enuresis usually can be managed effectively by the primary care provider. However, children with refractory or nightly nocturnal enuresis may benefit from referral to a healthcare professional who specializes in the management of recurrent or refractory enuresis (eg, developmental-behavioral pediatrician or urologist if structural or anatomic abnormalities are suspected) [4,5]. Additional indications for referral include non-monosymptomatic enuresis; developmental, attentional, or learning difficulties; behavioral or emotional problems; known or suspected physical or neurologic problems, and parents who are having emotional difficulty coping with bedwetting or are expressing anger, negativity, or blame.
Initial management — Initial management of enuresis usually involves education and motivational therapy and is directed by the primary care provider.
Education and advice — The guidelines of the International Children's Continence Society, National Institute for Health and Care Excellence, and Paediatric Society of New Zealand recommend the provision of basic education/advice for children and caregivers of children with nocturnal enuresis as the initial step in management [4-6]. The education and advice typically includes the following information:
●Enuresis is common; it occurs at least once per week in 16 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'.)
●Enuresis is the fault of neither the child nor the caregivers; children should not be punished for bedwetting. (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Causes'.).
●The impact of bedwetting can be reduced by using bed protection and washable/disposable products; using room deodorizers; thoroughly washing the child before dressing; and using emollients to prevent chafing.
●Keeping a calendar of wet and dry nights helps to determine the effect of interventions. (See "Nocturnal enuresis in children: Etiology and evaluation", section on 'Voiding diary'.)
●The child should attempt to void regularly during the day and just before going to bed (a total of four to seven times); if the child wakes at night, the caregivers should take him/her to the toilet.
●High-sugar and caffeine-based drinks should be avoided in children with enuresis, particularly in the evening hours.
●Daily fluid intake should be concentrated in the morning and early afternoon; fluid and solute intake should be minimized during the evening. Some authors recommend that their enuretic patients drink 40 percent of their total daily fluid in the morning (7 a.m. to 12 p.m.), 40 percent in the afternoon (12 p.m. to 5 p.m.), and only 20 percent in the evening (after 5 p.m.) . Ample consumption of fluid in the morning and afternoon reduces the need for significant intake later in the day. Isolated nighttime fluid restriction, without compensatory increase in daytime fluid consumption, may prevent the child from meeting his or her daily fluid requirement and is usually unsuccessful. (See "Maintenance fluid therapy in children", section on 'Components of 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) .
Motivational therapy — Once the child agrees to accept some responsibility for the treatment program, he or she 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 . Successively larger rewards, agreed upon in advance, are given for longer compliance with 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 (ie, removal of previously gained rewards) are counterproductive .
Motivational therapy is a good first-line therapy for nocturnal enuresis in younger children (between five and seven years of age) who do not wet the bed every night [5,12,17]. Motivational therapy is estimated to be successful (14 consecutive dry nights) in 25 percent of children and to lead to significant improvement (decrease in enuretic events by ≥80 percent) in more than 70 percent [18,19]. The relapse rate (more than two wet nights in two weeks) is approximately 5 percent . In a systematic review of simple behavioral interventions for nocturnal enuresis, reward systems (eg, star charts) were associated with fewer wet nights, higher cure rates, and lower relapse rates than no treatment, but these results were based on single small trials .
If motivational therapy fails to lead to improvement after three to six months, the addition of active interventions may be warranted .
Addition of active therapy — Enuresis alarms and desmopressin are effective active therapies for nocturnal enuresis [4,21,22]. Each has advantages and disadvantages. The best active intervention for a particular child depends upon how soon a response is desired, the motivation and commitment of the child and family, and the frequency and volume of enuresis.
Enuresis alarms are the most effective long-term therapy and have few adverse effects. However, they require a long-term commitment (usually three to four months). We suggest an enuresis alarm as the initial active therapy for highly motivated children and families when the child has frequent enuresis (more than twice per week) and short-term improvement is not a priority. (See 'Enuresis alarms' below.)
Oral desmopressin works best for children with nocturnal polyuria and normal functional bladder capacity. It may be more effective than an enuresis alarm in the short-term, but has a higher relapse rate and is more expensive. We suggest desmopressin as the initial active therapy for children and families who seek short-term improvement of enuresis; have failed, refused, or are unlikely to adhere to alarm therapy; or for whom an enuresis alarm is unsuitable. (See 'Desmopressin' below.)
Enuresis alarms — Enuresis alarms are activated when a sensor, placed in the undergarments or on a bed pad, detects moisture; the arousal devise is usually an auditory alarm and/or a vibrating belt or pager (figure 2 and table 1) [9,12]. The type of alarm should be tailored to the child's needs and abilities. The alarms work through conditioning: the child learns to wake or inhibit bladder contraction in response to the physiologic conditions present before wetting.
Indications and contraindications — Enuresis alarms are a first-line treatment for children whose bedwetting has not responded to advice about fluid intake, toileting, or an appropriate reward system . Enuresis alarms work best for well-motivated families and children with frequent enuresis (more than twice per week) [4,5]. They may be used in children younger than seven years, depending upon the child's ability, motivation, and understanding of the alarm. The child must be able to wake to sound or touch for the alarm to work; it is helpful to test this ability before the enuresis alarm is prescribed or purchased .
Other treatment options should be used if :
●Rapid or short-term improvement is the goal (desmopressin is a better option)
●The child or parents do not want to try the enuresis alarm (other options include desmopressin or simple alarm clock training)
●The child wets the bed only once or twice per week and this frequency is not problematic (continue motivational therapy)
●The parents are having emotional difficulty coping with the burden of bedwetting (desmopressin is a better option; referral to a healthcare professional who specializes in the management of enuresis may be warranted) (see 'Indications for referral' above)
●The parents are expressing anger, negativity, or blame toward the child (desmopressin is a better option; referral to a healthcare professional who specializes in the management of enuresis may be warranted) (see 'Indications for referral' above)
Efficacy — Enuresis alarms are the most effective means of controlling nocturnal enuresis and preventing relapse [21,23-25]. In a meta-analysis of 56 randomized trials (3257 children), the following results were noted :
●Sixty-six percent of children became dry for 14 consecutive nights during alarm use versus only 4 percent of no-treatment controls (relative risk [RR] for treatment failure 0.38, 95% CI 0.33-0.45).
●Nearly one-half of children who continued to use the alarm remained dry after treatment, compared with almost none in the no-treatment group (45 versus 1 percent, RR for relapse 0.56, 95% CI 0.46-0.68).
●During the first week of treatment, children had fewer wet nights with desmopressin than alarms (weighted mean difference 2.1, 95% CI 0.99-3.21); toward the end of treatment, they had fewer wet nights with alarms, but this result was not statistically significant.
●Alarms were more effective than tricyclic antidepressants during and after treatment. Treatment with tricyclic antidepressants is discussed below. (See 'Tricyclic antidepressants' below.)
Instructions and adverse effects — The family should be instructed that the child is in charge of the alarm . Each night before he or she goes 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 [4,5,26]:
●The child turns off the alarm, gets up, and finishes voiding in the toilet (only the child should turn off the alarm). At the initiation of therapy, the child may occasionally fail to awaken; this can be ameliorated if the parents wake the child when the alarm sounds. The child's being fully awake and cognizant of what is happening is critical to the success of alarm therapy.
●The child returns to the bedroom.
●The child changes the bedding and underwear.
●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.
Changes of linen and clothing should be kept near the bed. The parents may need to help the child wake to the alarm and should supervise the changing of bed linens. A diary should be kept of wet and dry nights. Positive reinforcement should be provided for dry nights as well as successful completion of the above sequence of events. Penalties (eg, the removal of a reward) for wetting episodes appear to be counterproductive . (See 'Motivational therapy' above.)
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 [8,27,28]. Adverse effects of alarms 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 .
Monitoring response — The child should be seen in follow-up (or have telephone follow-up) within one to two weeks of initiating alarm therapy [5,8]. Subsequent management depends upon the initial response:
●Early signs of response – Treatment should be continued 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 a minimum of 14 consecutive dry nights [5,20]. This usually takes between 12 and 16 weeks, with a range of 5 to 24 weeks . If, after three months of alarm therapy, the child has not achieved complete dryness (14 consecutive nights), but has fewer wet nights, alarm therapy should be continued . 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 (more than two wet nights in two weeks). Children who relapse after discontinuation of the alarm usually can achieve a rapid secondary response due to preconditioning as a result of the first treatment program. (See 'Refractory enuresis' 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), the authors of this topic review 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. (See 'Administration and adverse effects' below.)
Desmopressin — Desmopressin (a synthetic vasopressin analog) is a first-line treatment for enuresis in children older than five years whose bedwetting has not responded to advice about fluid intake, toileting, or an appropriate reward system [4,5]. It is an alternative to enuresis alarms for children and families who seek rapid or short-term improvement of enuresis; have failed, refused, or are unlikely to adhere to enuresis alarm treatment; and for whom an enuresis alarm is unsuitable. (See 'Enuresis alarms' above.)
Indications/contraindications — Desmopressin works best for children with nocturnal polyuria and normal functional bladder capacity [4,29]. Nocturnal polyuria is defined by nocturnal urine production greater than 130 percent of expected bladder capacity for age . By convention, expected bladder capacity (in mL) is estimated with the following formula: 30 x (age [in years] +1) . Compared with other modes of therapy, desmopressin is relatively expensive . Desmopressin should not be used in children with hyponatremia or a history of hyponatremia .
Efficacy — Approximately 30 percent of patients achieve total dryness using desmopressin, with perhaps another 40 percent exhibiting a significant decrease in nighttime wetting . However, the relapse rate after discontinuation is high (60 to 70 percent) . In a systematic review of 47 randomized trials (3448 children) comparing desmopressin with other drugs or alarms in the treatment of nocturnal enuresis, the following findings were noted :
●Compared with placebo, desmopressin reduced bedwetting by 1.34 nights per week (95% CI 1.11-1.57).
●Compared with placebo, children treated with desmopressin were more likely to become dry (ie, no episodes for 14 nights) (81 versus 98 percent, relative risk [RR] of failure 0.84, 95% CI 0.79-0.91)
●In contrast to arousal alarms, treatment effects were not sustained after discontinuation of therapy (the rate of failure or relapse was 65 and 46 percent with desmopressin and alarms, respectively; RR of failure 1.42, 95% CI 1.05-1.91)
●Desmopressin and tricyclic antidepressants appear to be equally effective.
Administration and adverse effects — Desmopressin is administered in the late evening to reduce urine production during sleep. It is given orally (the intranasal formulation was associated with increased risk of hyponatremic seizures and is no longer indicated for the treatment of enuresis) . The dose is titrated to best effect. The anti-enuretic effect is seen immediately once the correct dose is achieved .
The dose and timing of administration depend upon the formulation. Regular tablets (the only formulation available in the United States) are given one hour before bedtime [4,14]. The initial dose is 0.2 mg (one tablet); if needed after 10 to 14 days, the dose may be increased by 0.2 mg to a maximum dose of 0.4 mg . Oral melt tablets are given 30 to 60 minutes before bedtime. The initial dose is 120 mcg; if needed after 10 to 14 days, the dose may be increased by 120 mcg to a maximum dose of 240 mcg .
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 in order to adequately titrate the dose and make sure that it will be effective.
Adverse effects of desmopressin therapy are uncommon. The most serious adverse effect is dilutional hyponatremia, which occurs when excess fluids are taken in the evening hours [31-33]. To prevent dilutional hyponatremia with oral desmopressin, it is recommended that fluid intake be limited to eight ounces (240 mL) from one hour before to eight hours after administration of desmopressin . Treatment with desmopressin should be interrupted 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 bedwetting .
Assessing response — The response to desmopressin should be assessed within one to two weeks . 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) . 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 [4,5].
Lack of response to desmopressin 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) [14,29,34].
Discontinuation — When discontinuing daily desmopressin, we suggest that the dose be tapered (as described below) rather than discontinued abruptly.
Tapering the dose may decrease the rate of relapse. A multicenter randomized trial compared four discontinuation regimens in 259 children with nocturnal enuresis who responded to desmopressin: administration of one-half of the effective dose for two weeks before discontinuation; administration of the effective dose every other day for two weeks before discontinuation; administration of placebo for two weeks before discontinuation; and abrupt discontinuation without placebo . Relapse (>2 nights of bedwetting per month) rates at 12 weeks were lower in the groups with tapered withdrawal (39 and 42 percent) than in the placebo and abrupt discontinuation groups (53 and 55 percent, respectively).
Treatment of relapse — Relapse is defined by more than one wet night per month after a period of dryness . Treatment of relapse varies depending upon the initial management.
The initial response is to reinitiate whatever intervention was effective in the past [5,8]. For children with multiple recurrences after discontinuation of desmopressin, it may be helpful to try tapering desmopressin gradually, rather than stopping it suddenly . (See 'Enuresis alarms' above and 'Desmopressin' above.)
Combination alarm and desmopressin therapy may be beneficial for children who have more than one recurrence following successful treatment with an alarm. In a meta-analysis, children treated with combination desmopressin and alarm therapy had fewer wet nights than children treated with alarms alone (weighted mean difference -0.83, 95% CI -1.11 to -0.55) . However, failure and relapse rates did not differ.
Etiology and evaluation — Nonresponse to active intervention is defined by <50 percent improvement in symptoms . When motivated children and families do not respond to an adequate trial of treatment with an enuresis alarm (ie, three months) and/or desmopressin (at a dose of 0.4 mg), referral to a healthcare professional who specializes in the management of bedwetting that has not responded to initial treatment (eg, developmental-behavioral pediatrician, pediatric urologist) may be warranted [4,5].
Possible reasons for lack of response include:
●Overactive bladder (see "Etiology and clinical features of bladder dysfunction in children", section on 'Overactive bladder')
●Underlying disease (eg, diabetes mellitus)
●Incorrect use of alarm (see 'Enuresis alarms' above)
●Occult constipation (it may be helpful to ask about soiling in addition to the usual questions about bowel habits)
●Social and emotional factors
Additional evaluation of such children may include :
●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
●Rectal examination, anorectal manometry, or abdominal radiographs to look for occult constipation [37,38]
Following additional evaluation to exclude other causes of enuresis, management of therapy-resistant monosymptomatic nocturnal enuresis may include [4,5,24,39]:
●Desmopressin alone if continued use of the alarm is no longer acceptable to the child or parents or if there was a partial response to combination treatment with desmopressin and an alarm after initial treatment with an alarm (see 'Desmopressin' above)
●A trial of a tricyclic antidepressant
Tricyclic antidepressants — Tricyclic antidepressants (TCAs) decrease the amount of time spent in REM sleep, stimulate vasopressin secretion, and relax the detrusor muscle. Given the efficacy and safety of enuresis alarms and desmopressin, TCAs (eg, imipramine, amitriptyline, and desipramine) are a third-line treatment for monosymptomatic enuresis (eg, children who have failed alarm therapy and/or desmopressin) . When used to treat enuresis, TCAs usually are prescribed by healthcare providers who specialize in the management of bedwetting that has not responded to initial treatment .
In a systematic review, compared with placebo, treatment with tricyclic or related drugs was associated with a reduction of approximately one wet night per week . Approximately 20 percent of children became dry (14 consecutive nights) during therapy (versus 5 percent with placebo, RR for failure 0.77, 95% CI 0.72-0.83). The rate of relapse was 96 percent after discontinuation of therapy. TCAs and desmopressin were similarly effective during therapy.
Although other TCAs are effective, imipramine is used most often in the treatment of enuresis. It is the only TCA recommended by the National Institute for Health and Care Excellence guidelines . Imipramine should be administered one hour before bedtime . Imipramine is supplied in 10 mg, 25 mg, and 50 mg tablets. The initial dose is 10 to 25 mg at bedtime and may be increased by 25 mg if there is no response after one week. On average, the bedtime dose is 25 mg for children five to eight years of age and 50 mg for older children. The dose should not exceed 50 mg in children between 6 and 12 years of age and 75 mg in children ≥12 years of age.
The response to imipramine should be assessed after one month. If there is no improvement after three months, it should be discontinued; imipramine should be discontinued gradually . 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 .
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 in order to titrate the dose adequately and make sure that it will be effective.
Adverse effects of TCA therapy are relatively uncommon. 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 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 . Before initiation of therapy with TCA, a thorough cardiac history and family cardiac history should be obtained. A family history of a first-degree relative with premature (<40 years of age) cardiac problems or a personal history of cardiac disease warrants a consultation with a pediatric cardiologist before starting a TCA . The pretreatment evaluation also should include a complete history and physical examination, with particular attention to weight, blood pressure and pulse rate, and a baseline electrocardiogram . TCA therapy should not be initiated unless these parameters are within the normal limits for the child's age, sex, and height. (See "Tricyclic antidepressant poisoning", section on 'Clinical features' and "Pediatric unipolar depression and pharmacotherapy: General principles", section on 'Pretreatment evaluation'.)
OTHER INTERVENTIONS — A number of other interventions have been used for nocturnal enuresis or refractory nocturnal enuresis. These include waking the child to urinate, bladder training exercises, anticholinergic and other drugs, and complementary and alternative therapies.
Waking the child to urinate — These interventions involve waking the child to use the bathroom after he or she has fallen asleep. Older children may use an alarm clock to wake themselves. Critics of these interventions suggest that they may keep the bed dry but do not teach the child to wake to the sensation of a full bladder . Nonetheless, in single, small trials, waking the child to urinate has been associated with fewer wet nights, higher cure rates, and lower relapse rates than no treatment [17,43].
We do not suggest waking the child to urinate. The International Children's Continence Society guidelines indicate that, "If the parents have a habit of waking the child at night to go to the toilet, they should be informed that it is allowed but not needed and would only help for that specific night, if at all" . The National Institute for Health and Care Excellence (NICE) guidelines suggest that waking the child may be used as a practical measure in the short-term management of bedwetting (to reduce the burden of clean-up) but does not promote long-term dryness . Other authors suggest that these interventions may be helpful for young children (eg, four to five years of age) who wet the bed only once per night and have motivated parents [44,45]. Waking also may be helpful for children ≥8 years who have not responded to initial treatments and choose parental waking over enuresis alarms or an alarm clock .
Alarm clocks — It may be possible to condition older children to wake to void by using an alarm clock (or mobile phone alarm) . In one study, 125 children (7 to 21 years of age) with primary nocturnal enuresis were enrolled in two treatment groups and treated for four months . Group I children were awakened to void when the bladder was full, but they remained dry (the waking time was determined individually during a one- to three-week trial period); group II children were awakened after two to three hours of sleep (whether they were wet or dry). One-third of the patients stopped using the alarm within one month. Among those who continued, initial success (14 consecutive dry nights) was obtained in both groups (77 percent in group I and 62 percent in group II). The relapse rate six months after stopping therapy was 24 percent for group I and 15 percent for group II. The authors concluded that an ordinary alarm clock is a safe, effective, noncontact treatment strategy for enuresis that does not require an episode of bedwetting to initiate a conditioning response.
Bladder training — Bladder training, also known as retention control training, involves asking the child to hold his or her urine for successively longer intervals to increase bladder capacity. Bladder training is a common component of multimodal therapy programs. We do not recommend bladder training in the initial management of monosymptomatic nocturnal enuresis.
In randomized trials, bladder training exercises increased bladder capacity [47,48]. However, increased bladder capacity was not associated with improved enuresis or improved response rate to subsequent treatment with an enuresis alarm [47,48]. 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 .
The NICE guidelines recommend against strategies that promote the interruption of urinary stream or encourage infrequent passing of urine during the day . The Paediatric Society of New Zealand guidelines recommend against bladder training as an initial treatment .
Anticholinergic drugs — Monotherapy with anticholinergic drugs, such as oxybutynin, is not effective in treating monosymptomatic nocturnal enuresis [49,50]. 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 [51-55]. (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 . 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 .
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 .
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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient information: Bedwetting in children (The Basics)")
●Beyond the Basics topics (see "Patient information: Bedwetting in children (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Primary monosymptomatic 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 lower urinary tract symptoms, and have no history of bladder dysfunction. (See 'Terminology' above.)
●Primary monosymptomatic enuresis has a high rate of spontaneous resolution (approximately 15 percent per year). (See 'Natural history' above.)
●Management of primary nocturnal enuresis may involve one or a combination of interventions. Education and motivational therapies usually are tried initially. More active intervention is warranted as the child gets older, social pressures increase, and self-esteem is affected. (See 'Overview' above.)
●General education and advice about bedwetting should be provided to all children and families of children with monosymptomatic enuresis. It is important to emphasize that enuresis is not the child's fault; provide practical suggestions to reduce the impact of bedwetting; encourage regular voiding during the day and just before going to bed; and provide guidelines about the timing and type of fluid intake. (See 'Education and advice' above.)
●Motivational therapy (eg, a star chart) is usually the first intervention for younger children (between five and seven years) who do not wet the bed every night and are mature enough to accept some responsibility for treatment. If motivational therapy fails to lead to improvement after three to six months, active interventions may be warranted. (See 'Motivational therapy' above.)
●Enuresis alarms (figure 2) and desmopressin are effective interventions for nocturnal enuresis in children and families who desire active treatment. The choice of intervention for a particular child depends upon how soon a response is desired, the motivation and commitment of the child and family, and the frequency and volume of enuresis. (See 'Addition of active therapy' above.)
•Enuresis alarms are the most effective long-term therapy and have few adverse effects. However, they require a long-term commitment (usually three to four months). We suggest an enuresis alarm as the initial active therapy for highly motivated children and families when the child has frequent enuresis (more than twice per week) and short-term improvement is not a priority (Grade 2A). (See 'Enuresis alarms' above.)
•Oral desmopressin works best for children with nocturnal polyuria and normal functional bladder capacity. It may be more effective than an enuresis alarm in the short-term, but has a higher relapse rate and is more expensive. We suggest desmopressin as the initial active therapy for children and families who seek short-term improvement of enuresis; have failed, refused, or are unlikely to adhere to alarm therapy; or for whom an enuresis alarm is unsuitable (Grade 2A). (See 'Desmopressin' above.)
●When motivated children and families do not respond to an adequate trial of treatment with an enuresis alarm and/or desmopressin, referral to a healthcare professional who specializes in the management of bedwetting may be warranted. (See 'Refractory enuresis' above.)
●The treatment of relapse varies depending upon the initial management. The initial response is to reinitiate whatever intervention was effective in the past. (See 'Treatment of relapse' above.)
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