What is the Most Effective Treatment for Primary Nocturnal Enuresis?

Patient Presentation
A 7.5-year-old male comes to clinic because of enuresis.
He wets 5 nights out of the week and has never been dry at night in the past. He was toilet trained at 3.5 years for bowel and daytime bladder with no difficulty. He voids 5 times/day.
He restricts fluids after mealtime at night. He takes no medications and is a second grader doing well.
His past medical history shows he is healthy with no other complaints.
For the family history his mother says that father denies bedwetting problems but that dad’s brother had problems.
The review of systems reveals no frequency, urgency, pain, daytime urinary problems such as stream problems, incontinence, or dribbling. He also has no stooling problems and no developmental/neurological problems.
The pertinent physical exam shows normal growth. His abdominal, rectal and genitourinary examinations are normal. Additionally his back shows no dimples or abnormal hair patterns. His neurological examination is normal including bilateral cremasteric reflexes and anal winks.
The laboratory evaluation included a urinalaysis and urine culture which also were normal.
The diagnosis of primary nocturnal enuresis was made. The family was counseled regarding the unlikelihood of an organic underlying cause of the enuresis and told his enuresis was most likely due to neurodevelopmental maturation.
They were counseled as to the natural history and treatment options. The boy was very motivated to try to become dry at night and a bed alarm system was prescribed. He was to return to clinic after two weeks of using the alarm.

Enuresis comes from the Greek – Enourein – to void urine. It functionally means voiding urine where it should not be urinated either day or night. In contrast, nocturia means voiding urine at night in the proper place and its cause is commonly habitual.
Primary Nocturnal Enuresis (PNE) is persistent bedwetting in the absence of any urologic, medical or neurological anomaly in a child beyond the age when over 75% of children are normally dry. A practical definition of PNE
is bedwetting more than 2x/month after the age of 6 years for females or after 7 years for males.

PNE is very common. Depending on the study, approximately 7% of 7 years olds have PNE. PNE in the adult population is about 0.5-1%, again depending on the study. It is more common among males and also appears to have a genetic predisposition as the incidence increases with the number of parents who also had PNE and in monozygotic twins.

The exact cause of PNE is not entirely know but appears to be a neurodevelopmental problem which is probably multifactorial.

  • Psychosocial – no relationship to social background, life stresses, family constellation, or number of residencies has been shown. Enuresis may be a symptom seen in people with underlying psychological problems but is not a psychological problem itself.
  • Caffeine – has a well-documented diuretic activity. Generally enuretics ingest a moderate amount of caffeine.
  • Genetics – associated with the genes 13q and 12q (possibly 5 and 22 also). As noted above there is in increased incidence in families and monozygotic twins.
  • Anti-diuretic hormone (ADH) production – Normally ADH increases at night. This increase doesn’t occur in child enuretics, but does occur in adolescent enuretics. The diurnal change may not be seen until ~age 10.
  • Sleep disturbance – Currently data cannot support that there is a definitive sleep disturbance, i.e. enuretics sleep “harder” or are more difficult to wake. However, there is some evidence that the change in ADH may also be linked to some difficulties in light sleep to awake transition. For instance, enuretics do not awaken to sound as easily as non-enuretics. This may be related to changes in delta wave activity between enuretics and non-enuretics.
  • Decreased bladder capacity – Current data does support increased bladder tone in some enuretics, which functionally would decrease bladder capacity.

Prognosis of PNE is excellent with ~15% of enuretics having spontaneous resolution per year.

Learning Point
The most effective treatment for PNE depends on the particular child. The most important variables being the age of the child, and the motivation of the child and family.
All treatment options should include discussion of the cause and natural history. PNE is not the child’s fault but some studies report that 20-36% of parents punish their children for bed-wetting. Punishment has been shown to decrease the success of treating the problem. Doing nothing also is always an option as the spontaneous resolution rate is approximately 15% per year and the child may truly outgrow the problem.

Other treatment options include

  • Bed Alarms – These have the highest success rate at 75-85% with only 10-20% relapse. Retreatment has even higher success rates. These work by conditioning where the child learns to waken to the urge to urinate.
    Most children are generally dry in 6-8 weeks. Use of the alarm can stop after 1 month of being continually dry. This usually takes 2-3 months total of using the alarm.
    Realistic goals should be set such as only waking to the alarm the first week, waking and getting up without help the second week, etc.
    Success is measured by smaller and smaller urine puddles before the first dry night. The cost is ~$50-75. The side effects are the distruptions of noise waking family members, having to wake up/change bedclothes, etc.

  • Medication – These generally work well while the medication is being taken but the relapse rate is high once the medications are stopped. The medications also may have side effects.
    • DDAVP (i.e. ADH or Desmopressin) works by increasing urine concentration and decreasing volume. It has a ~22% long term success rate. It is often very good for short term use such as sleep overs or camp. The cost is approximately $50-150 per month.
      Oral medication dosing is 0.2 milligrams at bedtime. This may be increased to 0.6 milligrams.
      Intranasal medication is also available.
      Side effects include possible water intoxication and some people recommend no more than 8 ounces of fluid to be drunk when DDAVP has been taken.

    • Oxybutynin chloride is an anticholinergic, antispasmodic used to decrease contractions.
      The success rate is 33% for polysymptomatic nocturnal enuresis while on the medication. It costs ~$10 per month.
      Oral dosing is 5 milligrams twice a day which may be increased to 20 milligrams a day.

    • Imipramine (Tofranil) is a tricyclic Antidepressant with anticholinergic properties that relax the detrusor muscle and increase the tone of the bladder neck. It has a small therapeutic window and can cause death with an overdose.
      It is generally used when co-morbid conditions exist such as attention deficit disorder or depression. Success rates are 10-60% and the relapse rate is ~90%.
      The cost is $8 per month.
  • Simple Behavioral Interventions such as sticker charts may be useful when used with alarms or other treatments. By themselves they have an 18% success rate. Overlearning (i.e. giving children extra fluids at bedtime after successfuly becoming dry using the alarm system) decreases the relapse rate of bed alarms.
  • Complex Behavioral Interventions such as dry bed training may or may not be helpful.
  • Psychotherapy – enuresis is a symptom not a cause of psychiatric problems. Treatment should be directed toward underlying psychological problems and data does not support this as primary treatment for enuresis.

Questions for Further Discussion
1. Whaat are the causes of diurnal enuresis?
2. What are the treatment options for diurnal enuresis?
3. What questions are important in the history?
4. What areas of the physical examination are important and why?

Related Cases

To Learn More

To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Bedwetting (Enuresis).

Neveus T, Lackgren G, Tuvemo T, Hetta J, Hjalamas K, Stenberg A. Scand J Urolo Nephrolo Suppl 2000;206:1-44.

Jalkut MW, Lerman SE, Churchill BM. Enuresis. Ped Clin North America 2001;48: 1461-1488.

Thiedke, CC. Noctural Enuresis. American Family Physician. 2003;67;1499-106, 1509-10.

Glazener CMA, Evans JHC, Peto RE. Alarm Interventions for Noctural Enuresis in Children. Cochrane Database of Systematic Reviews. Available from the Internet at http://www.cochrane.org/cochrane/revabstr/AB002911.htm (rev.2/26/05, cited 3/24/05).

Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

April 4, 2005