Finns dokumenterad effekt av tricykliska antidepressiva vid enuresis nocturna? Finns något koncentr

Fråga: Finns dokumenterad effekt av tricykliska antidepressiva vid enuresis nocturna? Finns något koncentrations-effekt samband?

Sammanfattning: Few studies have investigated the possible relationship between plasma concentrations and clinical effects of tricyclic antidepressants in the treatment of nocturnal enuresis in children. Although some evidence for such a correlation has found, it is intriguing and needs further study including a larger number of patients.

Svar: The efficacy of tricyclic antidepressants, particularly imipramine, in the treatment of enuresis in children has been demonstrated in several controlled clinical trials (1). Generally it is not recommended to use tricyclic antidepressants in children under 5-6 years of age (1).

Interindividual differences in steady-state plasma concentrations of imipramine have been found in children (2) as in adults. The possible relationship between plasma concentrations and therapeutic and toxic effects of imipramine in the treatment of nocturnal enuresis was studied in 22 hospitalized children by Jörgensen et al (3). A significant correlation was found between steady-state plasma concentrations of imipramine + desipramine and reduction in enuresis frequency. The optimum effect was observed when steady-state levels of imipramine + desipramine were above 60 ng/ml.

In 10 enuretic children treated with clomipramine, a therapeutic effect was observed at clomipramine concentrations of 20-60 ng/ml, while lower or higher levels were associated with lack of therapeutic effect or adverse effect (4). Plasma levels of desmethylclomipramine were not included in the analysis of the date.

Rapoport et al (5) studied the effect of impramine and desipramine in 40 enuretic boys. Plasma levels of desipramine and imipramine plus desipramine correlated significantly with the antienuretic effect, but although significant, these correlations were low. At follow-up true non-responder were detected. There was no evidence of a therapeutic "window" and plasma levels of drug were correlated with effect only after a relatively short time. 1 Drugline nr 02152 2 Winsberg BG, Perel JM, Jurwic MJ, Klutch A: Imipramine protein binding and pharmacokinetics in children. IN: Forrest, Carr and Usdin (Eds). The phenothiazines and structurally related drugs, pp 425-431, Raven press, New York 1974 3 Jörgensen OS, Lober M, Christiansen J, Gram L: Plasma concentration and clinical effect in imipramine tratment of childhood enuresis. Clin Pharmacokinet 1980; 5: 386-393 4 Dugas M, Zarifien E, Leheuzey MF, Rovei V, Durand G, Morselli PL: Preliminary observations of the significance of monitoring tricyclic antidepressant plasma levels in the pediatric patient. Ther Drug Monit 1980; 2: 307-314 5 Rapoport JL, Mikkelsen EJ, Zavadil A, Nee L, Gruenav C, Mendelseon W, Gillin JC: Childhood enuresis. II. Psycopathology, tricyclic concentration in plasma, and antienuretic effect. Arch Gen Psychiatry 1980; 37: 1146-1152