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December 14, 1994

The Toxicity and Dose of Desipramine Hydrochloride

Author Affiliations

Hadassah Hospital Jerusalem, Israel
Rush-Presbyterian-St Luke's Medical Center Chicago, Ill

JAMA. 1994;272(22):1719-1720. doi:10.1001/jama.1994.03520220013006

To the Editor.  —Desipramine hydrochloride has been associated with a disproportionately high fatality rate. The relative risk of death from desipramine in suicide attempt is twofold to threefold higher than that of other tricyclic antidepressants.1,2 Sudden deaths have occurred in three children treated with desipramine for attention deficit disorder (Med Lett. June 1,1990). Outcome data from overdoses with four tricyclic antidepressants for the years 1989 through 1992 (Table) show a significantly higher fatality rate from desipramine (P<.001). The increased relative toxicity of desipramine requires explanation.The pharmacokinetic data of four tricyclic antidepressants listed in the Table show a key difference between tertiary and secondary amines. The secondary amines desipramine and nortriptyline hydrochloride have higher distribution volumes, red blood cell (RBC)/plasma ratios, and a higher proportion of unbound (free) drug than their respective parent compounds, imipramine hydrochloride and amitriptyline hydrochloride. This distribution pattern implies that desipramine and nortriptyline have