Original ArticlesExcess Fatality from Desipramine and Dosage RecommendationsAmitai, Yona MD, MPH*; Frischer, Henri MD, PhD†Author Information From the *Department of Mother, Child and Adolescent Health, Ministry of Health, Jerusalem, Israel; and †Rush University Medical Center, Chicago Illinois. Received for publication March 18, 2004; accepted June 29, 2004. Reprints: Yona Amitai, MD, MPH, Department of Mother Child and Adolescent Health, Ministry of Health, 20 King David Street, Jerusalem 91010 Israel (e-mail: [email protected]). Therapeutic Drug Monitoring: October 2004 - Volume 26 - Issue 5 - p 468-473 Buy Abstract 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. © 2004 Lippincott Williams & Wilkins, Inc.