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Plasma concentration and clinical effect in imipramine treatment of childhood enuresis
Insights
Imipramine effectively treats childhood nocturnal enuresis, with optimal results seen at specific plasma concentrations. Higher imipramine and desipramine levels correlate with reduced enuresis frequency in children.
Area of Science:
- Pharmacology
- Pediatrics
- Clinical Therapeutics
Background:
- Nocturnal enuresis is a common condition in children.
- Imipramine is a tricyclic antidepressant used off-label for enuresis.
- Understanding the pharmacokinetic-pharmacodynamic relationship of imipramine in children is crucial for effective treatment.
Purpose of the Study:
- To investigate the relationship between steady-state plasma concentrations of imipramine and its metabolite desipramine and the clinical effect in treating nocturnal enuresis in children.
- To determine the optimal therapeutic plasma concentration range for imipramine in pediatric enuresis treatment.
Main Methods:
- A study involving 22 hospitalized children with nocturnal enuresis.
- A 1-week placebo period followed by 3 weeks of fixed-dose imipramine (approx. 1 mg/kg).
- Measurement of plasma concentrations of imipramine and desipramine, and assessment of enuresis frequency.
Main Results:
- A significant decrease in enuresis frequency was observed after the first week of imipramine treatment, with no further improvement thereafter.
- A significant correlation was found between steady-state plasma concentrations of desipramine or imipramine + desipramine and the reduction in enuresis frequency.
- Optimal clinical effect was achieved when imipramine + desipramine plasma levels exceeded 60 microgram/L.
- Effective therapeutic concentrations for enuresis were 3 to 4 times lower than those for antidepressive therapy.
Conclusions:
- Steady-state plasma concentrations of imipramine and desipramine are significantly correlated with the therapeutic efficacy in pediatric nocturnal enuresis.
- The optimal therapeutic plasma concentration range for imipramine in treating childhood enuresis is lower than that required for depression.
- These findings support the use of therapeutic drug monitoring for imipramine in pediatric enuresis to optimize treatment outcomes.
Abstract:
The relationship between steady-state plasma concentraton and clinical effect of imipramine in the treatment of nocturnal enuresis was studied in 22 hospitalised children. After 1 week on placebo the children were given imipramine in a fixed dose of about 1 mg/kg for 3 weeks. The enuresis frequency decreased significantly from the placebo to the first week on imipramine, but then no further improvement was observed. There was a significant correlation between steady-state plasma concentration of desipramine or imipramine + desipramine and the reduction in enuresis frequency during imipramine treatment. The optimum effect was obtained when steady-state levels of imipramine + desipramine were above 60 microgram/L; i.e. the effective concentration in enuresis is 3 to 4 times lower than in antidepressive therapy. Dose- and weight-corrected, steady-state plasma concentration of imipramine and desipramine were not significantly different from those previously observed in younger adults. In 1 child, a transient rise in imipramine and desipramine concentration was seen during a period with fever and bacterial infection.