Enuresis imipramine

The two primary agents used to treat enuresis are desmopressin and imipramine (Table 50-7). Desmopressin is the drug of choice in pediatric enuresis. Anticholinergics have a limited role (Table 50-7). Other agents have been studied with inconclusive results.28... 

Children Not recommended for patients younger than 12 years of age. Safety and efficacy are not established for amoxapine in children younger than 16 years of age or trazodone or clomipramine in children younger than 10 years of age. The safety and efficacy of imipramine as temporary adjunctive therapy for nocturnal enuresis in pediatric patients younger than 6 years of age have not been established. The safety of the drug for long-term, chronic use as adjunctive therapy for nocturnal enuresis in pediatric patients 6 years of age and older has not been established. Safety and efficacy are not established in the pediatric age group for trimipramine, nortriptyline, protriptyline, and desipramine. 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Imipramine Tertiary Blockade of norepinephrine reuptake at 0.2 autoreceptor and blockade of serotonin reuptake at 5-HTi autoreceptor 13 2 42 2 Enuresis, age 6+ years... 

Multiple studies have been done of TCAs in the treatment of nocturnal enuresis, and all consistently show effect over placebo. Most notably, Rapoport et al. (1978) found a significant relationship between IMI plasma level and response to medication. Imipramine is the only medication with FDA approval for treatment of this condition. 

Rapoport, J.L., Mikkelsen, E.J., and Zavadil, A.P. (1978) Plasma imipramine and desmethylimipramine concentration and clinical response in childhood enuresis. Psychopharmacol Bull 14 60-61. 

Tricyclic antidepressants have been used for decades to treat depression and anxiety in the general population, and clomipramine has been used to treat OCD. Clomipramine has been studied with respect to treating school phobia or school refusal (Berney et ah, 1981). Gittleman-Klein and Klein (1971) found imipramine to be superior to placebo in treating school refusal. As the TCAs may improve other disorders such as nocturnal enuresis, ADHD, and sleep disorders, they may be attractive for children with any of these comorbid conditions and anxiety disorder. 

In 1995, Bramble published a study on the prescription frequency of antidepressants by British child psychiatrists (Bramble, 1995). A brief postal questionnaire was circulated to 350 members of the British Royal College of Psychiatrists, Child and Adolescent Psychiatry Specialist Sections. There was a 71% response rate, and 85% of the 238 respondents had employed antidepressants, the most popular of these being amitriptyline and imipramine. Nearly one-third of the psychiatrists at that time used neuroagents occasionally, and the SSRIs were used only very rarely. The antidepressant medication was used for a wide range of child and adolescent disorders beyond those of depression and nocturnal enuresis. Approximately 20% of the prescriptions were given for ADHD (hyperkinetic disorder), conduct disorder, and a few cases of autistic disorder. Clomipramine was apparently given for OCD. On the basis of these 1994 data. Bramble concluded that British child psychiatrists tend to use antidepressant medication far less often than American psychiatrists. 

Spurious hyperthyroidism occurred in a child taking thyroid hormone and imipramine for enuresis (89). The ability of thyroid hormone to increase receptor sensitivity to catecholamines has long been known, and has been used to enhance the clinical response in some refractory patients, especially women. 

The anticholinergic effect of imipramine has been used successfully in managing enuresis (Figure 43.5). 

The efficacy of imipramine has been repeatedly demonstrated in controlled trials about 85% of children treated within a week of the start of medication, but tolerance frequently develops after a number of weeks and relapse is high after discontinuation of the treatment. Relatively low doses of imipramine only are needed, but the typical side effects of tricyclic antidepressants limit the prolonged use of the drug. The mechanism of action of imipramine in the treatment of nocturnal enuresis is unclear but one possible action is through a direct anticholinergic action on the bladder wall. 

Preference of some prescribers for imipramine over other TCAs for the treatment of enuresis is based more upon art and anecdote and empiric clinical experience than comparative clinical trials with other TCAs... 

Tricyclic antidepressants represent a class of drugs widely prescribed for the treatment of endogenous depression and neuralgic pain, migraine headache, enuresis, and attention deficit disorder (see Chapter 33). Tricyclic antidepressants include imipramine, amitriptyline, and their N-... 

Imipramine and other TCAs are effective for enuresis at wide dosage ranges. TCAs have rapid onset, but side effects may be problematic for some patients. 

Overall, both desmopressin and TCAs are effective in the treatment of nocturnal enuresis as long as the drng is maintained. Drng selection is based on adverse-effect profiles, ease of administration, and cost. Imipramine has a higher adverse effect burden compared to desmopressin, and the risk of accidental overdose is of concern, especially in very disorganized families. In contrast, desmopressin is markedly more expensive than imipramine. 

Monda JM, Husmann DA. Primary nocturnal enuresis A comparison among observation, imipramine, desmopressin acetate and bedwetting alarm systems. J Urol 1995 154 745-748. 

Although several antidepressants are EDA-approved for use in children, only one, fluoxetine, is currently approved for childhood depression. Imipramine is approved for the treatment of enuresis, clomipramine for obsessive-compulsive disorder in children 12 years and older, and fluvoxamine along with fluoxetine is approved for obsessive-compulsive disorder in children. The treatment of depression in children remains challenging, as depression can be difficult to diagnose and treat once identified. The studies involving imipramine, sertraline, and fluoxetine found that the dose range and titration as well as adverse effects were similar to those in adults. " ... 

Tofranil imipramine tricyclic antidepressant ADHD, eating disorders, enuresis, depression sedation, dry mouth, changes in blood pressure, constipation... 

These drugs are used to alleviate depression, and are also used in the therapy of diabetic neuropathy. They may also be effective in the treatment of obsessive compulsive disorder (OCD) and attention-deficit hyperactivity disorder. Certain drugs of this class have also been therapeutically useful in the treatment of childhood enuresis (e.g., imipramine), fibromyalgia (e.g., amitriptyline), and chronic obstructive pulmonary disease (COPD) (e.g., protriptyline). 

OTHER THERAPEUTIC USES OE THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologicaUy to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nortriptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy. 

Besides being used in the ciinicai treatment of depression, imipramine aiso has been used for the treatment of functionai enuresis in chiidren who are at ieast 6 years of age (25 mg daiiy administered 1 hour before bedtime, not to exceed 2.5 mg/kg daiiy). 

The addition of liothyronine 25 micrograms daily was found to increase the speed and efficacy of imipramine in relieving depression. Similar results have been described in other studies with desipramine or amitriptyline but the reasons are not understood. One possible explanation is that the patients had overt or subclinical hypothyroidism, which after correction with liothyronine allowed them to overcome an impaired response to tricyclic antidepressants." However, adverse reactions have also been seen. A patient being treated for both hypothyroidism and depression with thyroid 60 mg and imipramine 150 mg daily complained of dizziness and nausea. She was found to have developed paroxysmal atrial tachycardia. A 10-year-old girl with congenital hypothyroidism, well controlled on desiccated thyroid 150 mg daily, developed severe thyrotoxicosis after taking imipramine 25 mg daily for 5 months for enuresis. The problem disappeared when the imipramine was withdrawn. In another patient the effect of levothyroxine was lost and hypothyroidism developed when dosulepin was started. ... 

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