Desipramine in children

Spencer, T. (1997) A double-blind, controlled study of desipramine in children with ADHD and tic disorders. In Scientific Proceedings of the Annual Meeting American Academy of Child and Adolescent Psychiatry, Toronto. Washington, DC American Academy of Child and Adolescent Psychiatry. 

Leonard, H., Swedo, S., Rapoport, J., Koby, E., Lenane, M., Cheslow, D., and Hamburger, S. (1989) Treatment of obsessive-compulsive disordet with clomipramine and desipramine in children and adolescents. Arch Gen Psychiatry 46 1088-1092. 

Clomipramine, fluvoxamine, sertraline, and fluoxetine are approved by the FDA for treatment of OCD in children and adolescents. Childhood and adult OCD appear to respond similarly to drug therapy. The SSRIs appear to be effective and well tolerated in treatment of OCD in children and are generally considered first-line agents. Treatment with an SSRI produces a favorable response in 75% of children and adolescents with OCD. A combination of SSRIs and CBT is preferred in most cases. In children, the most commonly described side effects of SSRI therapy include nausea, headache, tremor, gastrointestinal complaints, drowsiness, akathisia, insomnia, disinhibition, and agitation. Clomipramine was significantly better than placebo in the treatment of OCD in children and adolescents, with 75% of patients having a moderate to marked improvement. Clomipramine was also more effective than desipramine in children and adolescents. ... 

Cohen LG, Prince J, Biederman J, Wilens T, Faraone SV, Whitt S, Mick E, Spencer T, Meyer MC, Poliaier D, Flood JG. Absence of effect of stimulants on the pharmacdcinetics of desipramine in children Pharmacotherapy ( 999) 19,746-52... 

Several cases of sudden death have been reported in children and adolescents taking desipramine. A baseline electrocardiogram (ECG) is recommended before initiating a TCA in children and adolescents, and an additional ECG is advised when steady-state plasma concentrations are achieved. TCA plasma concentration monitoring is critical to ensure safety. 

DESIPRAMINE HYDROCHLORIDE Not recommended for use in children younger than 12 years of age. 

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. 

For some psychotropic drugs (e.g., lithium and some antidepressants) a good correlation exists between plasma levels and therapeutic or toxic effects. Optimum steady-state levels can now be predicted from single-dose blood level data of some drugs (lithium, nortriptyline, desipramine). Altered PK behavior in children has to be taken into consideration in using psychotropic drugs. With development of suitable drug... 

Pataki, C., Carlson, G., Kelly, K., and Rapport, M. (1993) Side effects of methylphenidate and desipramine alone and in combination in children./ Am Acad Child Adolesc Psychiatry 32 1065-1072. 

Biederman, J., Baldessarini, R., Goldblatt, A., Lapey, K., Doyle, A., and Hesslein, P. (1993a) A naturalistic study of 24-hour electrocardiographic recordings and echocardiographic finding in children and adolescents treated with desipramine. / Am Acad Child Adolesc Psychiatry 32 805-813. 

Biederman, J., Gastfriend, D.R., and Jellinek, M.S. (1986) Desipramine in the treatment of children with attention deficit disorder. J Clin Psychopharmacol 6 359-363. 

Leonard, H.L., Swedo, S.E., Lenane, M.C., Rettew, D.C., Cheslow, D.L., Hamburger, S.D., and Rapoport, J.L. (1991) A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder. Arch Gen Psychiatry 48 922—927. 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Biederman et al. (1989a,b) also found desipramine (at the relatively high mean dose of 4.6 mg/kg/day) to be safe and effective for treatment of ADD. Despite these positive results, however, concerns about prolonged cardiac conduction times and the reports of several sudden deaths of children on desipramine have left many clinicians and parents reluctant to use the drug (Riddle, et ah, 1993). Another less well-studied tricyclic, nortriptyline, which some believe to have less potential cardiotoxicity, has shown promise in a retrospective study in children with ADHD plus tic disorder (Spencer et al., 1993b). 

Leonard HL, Swedo SE, Lenane MC, et al A double-bhnd desipramine substitution during long-term CMl treatment in children adolescents with OCD. Arch Gen Psychiatry 48 922-927, 1991... 

A number of studies indicate that some but not all antidepressants are effective in ADHD. Spencer and colleagues (66) found 29 studies (involving 1,016 patients) that supported the efficacy of TCAs in the treatment of ADHD. Desipramine is the TCA with the most efficacy data. Desipramine, based on a meta-analysis of five randomized trials involving 170 ADHD patients had efficacy (i.e., effect size) comparable with that of methylphenidate ( 90, 91). However, desipramine produced a higher rate of adverse effects compared with psychostimulants. Moreover, several sudden, unexpected deaths have been reported in children on desipramine ( 92,... 

The adverse effects of TCAs are also similar to those reported in adults (see Chapter 7). The secondary amine TCAs (e.g., desipramine, nortriptyline) are generally as well tolerated as newer antidepressants. Increased blood pressure may be more likely to occur in children than in adults but hypertension per se is rare ( 135). The most common cardiovascular effect is mild tachycardia. Despite their generally favorable adverse effect profile, secondary amine TCAs can cause serious toxicity in children and adolescents just as in adults when a taken in an overdose or when a high TCA plasma level occurs as a result of slow metabolism ( 136). For that reason, most clinicians reserve TCAs for the child or adolescent who has at least a moderate depressive disorder unresponsive to a trial of one or more newer antidepressants. In such instances, TDM should be done at least once to ensure plasma concentrations greater than 450 ng/mL do not develop ( 137). Such levels are associated with an increased risk of the following ... 

Toxicity. In adults the estimated minimum lethal dose is 1 g, although fatalities have occurred with less and patients have survived the ingestion of as much as 5 g. In children, as little as 350 mg may be fatal. Blood concentrations greater than 0.5 jj-g/ml (imipramine and desipramine) may cause toxic effects and imipramine concentrations of 0.8 to 4.5 to 13 pg/ml have been associated with fatalities. 

Half-life. Plasma half-life, imipramine 8 to 20 hours, increased in children, elderly subjects, and after overdose desipramine 10 to 35 hours. 

Not recommended for first-line use in children with ADFID because of the availability of safer treatments with better documented efficacy and because of desipramine s potential for sudden death in children... 

Do not exceed plasma concentration of 225 mg/ml (imipramine plus its desipramine metabolite) in children, due to increased risk of cardiovascular effects at higher serum levels. 

The effects of TCAs on the electrocardiogram should be monitored carefully. Of more concern are reports of sudden death in children taking desipramine or imipramine. Children and adolescents given TCAs should have pretreatment and follow-up electrocardiograms to assess the effects of TCA therapy on cardiac rate and rhythm. ... 

Spencer T, Biederman J, Coffey B, et al. A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2002 59 649-656. 

Leonard HL, Meyer HC, Swedo SE, et al. Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents. J Am Acad Child Adolesc Psychiatry 1995 34 1460-1468. 

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. 

Desipramine (e.g., Norpramine) it Use increasing because of fewer anticholinergic effects. Less sedation, fewer anticholinergic effects. Sudden death in children has occurred. 

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