Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms.

In two unrelated cases, a 7-year-old boy and a 21-year-old woman died suddenly while receiving chronic imipramine therapy. In the boy, concentrations of imipramine were: Left femoral blood 0.5 mg/L, right femoral blood 1.2 mg/L, aorta blood 1.0 mg/L, liver 68 mg/Kg, and for the active metabolite, desipramine, left femoral blood 6.7 mg/L, right femoral blood 9.9 mg/L, aorta blood 8.7 mg/L, liver 400 mg/Kg. In the woman, the imipramine concentrations were: Femoral blood 0.6 mg/L, liver 37 mg/Kg, and of the active metabolite, desipramine, femoral blood 3.74 mg/L, liver 261 mg/Kg. In both cases, the scene investigation strongly indicated that neither individual had ingested an acute overdose. The very high ratios of desmethyl metabolite to parent drug are consistent with this observation. Impaired metabolism due to a genetically determined "slow metabolizer" phenotype of cytochrome CYP2D6, and/or concurrent therapy with phenothiazines, is suggested as a possible mechanism for the apparent fatal accumulation of these tricyclic antidepressants.

The investigation of beta-hydroxybutyrate as a marker for sudden death due to hypoglycemia in alcoholics.

The purpose of this study was to determine if the ketone body beta-hydroxybutyrate (beta-HBA) is a useful positive marker for sudden deaths in chronic alcoholics, thought to be due to hypoglycemia. Beta-HBA can be reliably measured in postmortem samples of vitreous humour and urine. In fatalities where there is a history of chronic alcoholism and routine investigations, including autopsy and routine toxicology, yield only a fatty liver as positive findings, a raised level of beta-HBA can be used as an indicator for alcoholic ketosis. Alcoholic ketosis is often associated with antemortem hypoglycemia. Caution should be observed in attributing the significance of ketosis exclusively to alcohol in those conditions where it would otherwise be expected (i.e. diabetic ketoacidosis and chronic starvation). A measurement of this marker of alcoholic ketosis may also help in the investigation of cases where hypothermia or alcohol withdrawal fits are suspected.

Tuberous sclerosis presenting as a suspicious sudden death--a case report and review of sudden deaths in epilepsy.

A case of a suspicious sudden death in a 19-year-old Caucasian female epileptic is presented. The brain showed characteristic lesions of tuberous sclerosis. In most sudden deaths in idiopathic epilepsy no causative lesion is found in the brain. A review of the past five years' cases attributed to sudden deaths in epilepsy from our department is presented, with particular reference to findings which might be construed as suspicious, e.g., signs of asphyxia and bruising in neck muscles, and to findings which support the diagnosis, e.g. biting of the tongue, voiding of urine, low levels of medication.