Urinary incontinence is a problem affecting 5% of 10% of the elderly in the community and up to 50% of the elderly in institutions. Despite complex factors governing normal micturition, the causes of urinary incontinence can be classified into detrusor instability, overflow incontinence, sphincter insufficiency, functional illness, and iatrogenic causes. An accurate pathophysiologic diagnosis is a prerequisite to successful treatment. A decision sequence is presented to help design a reasonable diagnostic approach. With appropriate therapy, most incontinent elderly patients can expect significant improvement or cure.

Urinary incontinence in the elderly: physiology, pathophysiology, diagnosis, and treatment.

Sleep disorders. Recent findings in the diagnosis and treatment of disturbed sleep.

Nocturnal urinary continence is dependent on 3 factors: 1) nocturnal urine production, 2) nocturnal bladder function and 3) sleep and arousal mechanisms. Any child will suffer from nocturnal enuresis if more urine is produced than can be contained in the bladder or if the detrusor is hyperactive, provided that he or she is not awakened by the imminent bladder contraction. Urine production is regulated by fluid intake and several interrelated renal, hormonal and neural factors, foremost of which are vasopressin, renin, angiotensin and the sympathetic nervous system. Detrusor function is governed by the autonomic nervous system which under ideal conditions is under central nervous control. Arousal from sleep is dependent on the reticular activating system, a diffuse neural network that translates sensory input into arousal stimuli via brain stem noradrenergic neurons. Disturbances in nocturnal urine production, bladder function and arousal mechanisms have all been firmly implicated as pathogenetic factors in nocturnal enuresis. The group of enuretic children are, however, pathogenetically heterogeneous, and two main types can be discerned: 1) Diuresis-dependent enuresis - these children void because of excessive nocturnal urine production and impaired arousal mechanisms. 2) Detrusor-dependent enuresis - these children void because of nocturnal detrusor hyperactivity and impaired arousal mechanisms. The main clinical difference between the two groups is that desmopressin is usually effective in the former but not in the latter. There are two first-line therapies in nocturnal enuresis: the enuresis alarm and desmopressin medication. Promising second-line treatments include anticholinergic drugs, urotherapy and treatment of occult constipation.

Enuresis--background and treatment.

This review provides a quantitative integration of research on the effectiveness of psychological and pharmacological treatments for nocturnal enuresis. With the use of experiments that compared treatments with either no treatment or another form of treatment, this article assesses (a) the overall effectiveness of psychological and pharmacological treatments, (b) the relative effectiveness of specific types of treatments, and (c) moderators of treatment effectiveness including investigator allegiance. Findings from the review confirm that enuretic children benefit substantially from treatment. However, more children improve from psychological than from pharmacological interventions. Moreover, psychological treatments involving a urine alarm are most likely to yield benefits that are maintained once treatment has ended.

https://drhouts.com/pdfs/14%20Houts%20Berman%20Abramson%20(1994)%20Metaanalysis%20JCCP.pdf

Effectiveness of Psychological and Pharmacological Treatments for Nocturnal Enuresis.

Background
Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s.

Objectives
To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis.

Search methods
We searched the Cochrane Incontinence Group Specialised Trials Register (containing trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings), on 30 November 2015, and reference lists of relevant articles.

Selection criteria
We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting.

Data collection and analysis
Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author.

Main results
Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.

Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.

Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).

There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.

Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).

Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.

Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.

At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).

When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response.

Authors' conclusions
There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.

Tricyclic and related drugs for nocturnal enuresis in children

IMIPRAMINE HYDROCHLORIDE (Tofranil) has been used since 1960 to treat the symptoms of enuresis. An unpublished review (by J. W. C.) of the research reported during 1960 to 1965 revealed 28 studies, of which only six used a control group and a large enough sample to give reliable results. 1-6 All six studies showed that imipramine did reduce enuresis significantly. In comparison with those 28 studies, this is the first study to meet all the following criteria: doubleblind technique; a large sample drawn from a presumed normal population of schoolchildren; and exclusion of other therapeutic attempts (such as counseling, psychotherapy, conditioning, habit training, etc). Methodology Twelve hundred letters were distributed among eight different grammar and high schools in Chicago and its suburbs. The letters were given to the school principals, who gave them to the teachers, who handed them to students in sealed envelopes with instructions to give them to

Imipramine in the Treatment of Enuretic Schoolchildren: A Double-Blind Study

Forty studies reporting the use of imipramine in the treatment of enuresis have been reviewed. All twenty-three of the uncontrolled studies report various degrees of success, and eleven of seventeen controlled studies also report successful results. The conclusion is that imipramine has a varied but statistically significant anti-enuretic effect on children.

https://journals.sagepub.com/doi/pdf/10.1177/070674376801300310

The use of imipramine in the treatment of enuresis. A review of the literature.

Mental health professionals are increasingly investing time and effort in the evaluation of their services. The present study describes one such evaluative effort undertaken by a children's Community Mental Health Center located in an inner cily neighborhood. Program results indicated that about two-thirds of children evidenced betler functioning following treatment. When presenting problems were categorized into distinct diagnostic entities, therapist ratings indicated that greater improvements were found with anxiety and situational problems, as compared to acting-out difficulties. Improvement was generally nor associated with demographic variables. On a follow-up consumer satisfaction questionnaire, children's parents reported being satisfied with the services provided at the Mental Healrh Center.

Frank A. Dinello

Papers

Imipramine in the Treatment of Enuretic Schoolchildren: A Double-Blind Study

The use of imipramine in the treatment of enuresis. A review of the literature.

Evaluating a Community Mental Health Center Program for Children