Excess Fatality from Desipramine and Dosage Recommendations

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.