ABSTRACT
OBJECTIVE: To compare the case fatality rate (CFR) from desipramine ingestion in children and adolescents with that of other tricyclic antidepressants. METHOD: All mentions of desipramine, amitriptyline, imipramine, nortriptyline, and doxepin in children and adolescents recorded in the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1983 to 2002 were analyzed. The CFR for each drug was defined as the ratio of the number of deaths/number of mentioned exposures. RESULTS: There were 24 fatalities in children younger than 6 years old (desipramine, n=10; amitriptyline, n=7; doxepin, n=3; imipramine, n=3; nortriptyline, n=1) and 144 fatalities in older children and adolescents (desipramine, n=56; amitriptyline, n=30; doxepin, n=16; imipramine, n=31; nortriptyline, n=11). The CFR from desipramine was significantly higher compared with the other tricyclic antidepressants in children younger than 6 years old (chi=36, p<.001) and in older children and adolescents (chi=155, p<.001). The CFR from desipramine exceeded that of amitriptyline, doxepin, imipramine, and nortriptyline by 7- to 8-, 4-, 6- to 12-, and 7- to 10-fold, respectively. CONCLUSIONS: The excess CFR from desipramine in children and adolescents and the reports of sudden death in children treated with therapeutic doses call for caution in prescribing desipramine to children and adolescents.
Subject(s)
Amitriptyline , Desipramine , Doxepin , Imipramine , Nortriptyline , Substance-Related Disorders/mortality , Adolescent , Child , Humans , Incidence , Mortality , PrevalenceABSTRACT
Higher case fatality rates (CFR) were previously reported from desipramine than for 3 other tricyclic antidepressants (TCAs): amitriptyline, nortriptyline, and imipramine. The database of the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) for the 20 years 1983-2002 was used to evaluate the CFR of desipramine and the other TCAs. The CFR of desipramine was 2.25-, 2.31-, and 2.62-fold the CFR for amitriptyline, nortriptyline, and imipramine, respectively (P < 0.001). Mechanisms of desipramine toxicity and its dosage recommendations are discussed. Desipramine and nortriptyline have higher distribution volumes and erythrocyte/plasma ratios than their parent compounds imipramine and amitriptyline. This implies lower therapeutic plasma levels and reduced doses for desipramine and nortriptyline compared with their parent compounds. Such adjustments have been done for nortriptyline, but not for desipramine. The authors suggest that the high CFR of desipramine might be reduced by lowering its dose, therapeutic plasma level, and maximal pill content.
