SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

P6
TWO CASES INVOLVING CLOMIPRAMINE INTOXICATION
Joseph Avella*, Michael Lehrer, Michael Katz and Edward Minden.
Suffolk County Office of the Medical Examiner, Toxicology Laboratory, Hauppauge NY.
Clomipramine and its active metabolite norclomipramine were identified and quantitated in multiple tissues
recovered from two postmortem cases using liquid chromatography/mass spectrometry (LCIMS). The
LCIMS method afforded the consistent chromatography needed to accurately determine both the parent
drug and the more polar metabolite while simultaneously providing the specificity associated with mass
spectral data.
In the first case a 23-year-old female with a history of depression presented to her attending pulmonologist
with a respiratory tract infection. She was diagnosed with pneumonia upon admission to the hospital. The
patient was placed on antibiotics and oxygen and appeared stable. Within twelve hours the patient became
confused and anxious. She began to have difficulty breathing and subsequently coded and expired despite
resuscitative efforts. An autopsy was conducted and tissues were submitted for toxicological analysis.
Clomipramine and norclomipramine was detected in the following concentrations: Heart blood; 1.39 mg/L
and 2.64 mg/L, Brain; 8.02 mg/kg and 26.74 mg/kg, Liver; 14.25 mg/kg and 41.12 mg/kg, Urine; 0.48
mg/L and 1.15 mg/L and Gastric Contents 3.99 mg/total and 0.61 mg/total.
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Case #2 was a 56-year-old female with a history of depression who had previously attempted suicide with
prescription painkillers. The evening prior to her death, the decedent had no complaints and retired for the
night. The following morning she was found dead in her bed. Autopsy revealed evidence of medication
around her mouth and in her gastric contents. No significant natural disease was present and toxicology
was requested to assess the possibility of an overdose. In this case clomipramine and norclomipramine was
detected in the following .amounts: Femoral blood; 0.70 mg/L and 0.66 mg/L, Pulmonary artery blood; 1.00
mg/L and 1.11 mg/L Brain; 4.86 mg/kg and 7.43 mg/kg, Liver; 11.68 mg/kg and 20.76 mg/kg, Gastric
21.20 mg/total and 1.34 mg/total and Small Intestinal contents; not detected and 0.10 mg/total. The other
significant finding was the presence ofhydro cod one in femoral blood at a concentration of0.13 mg/L.
In both cases the determination of clomipramine and metabolite in the brain samples was considered
especially useful for assessing toxicity. The author's found the brain to be helpful for several reasons.
First, although the blood results were potentially toxic, the liver results were not conclusively indicative of
an overdose. Patients that have undergone long-term tricyclics antidepressant (TCA) therapy can sequester
substantial amounts of parent drug and metabolite in liver, a particular concern because the TCA's may
exhibit postmortem redistribution. In some cases of TCA overdose the liver results are unmistakable (i.e.
clomipramine concentrations exceeding 200 mg/kg after acute poisoning). In the cases detailed in this
report the liver results were considered insufficient to confidently establish fatal toxicity. Blood specimens
(especially central) were viewed critically while interpreting results due to the concern of possible
postmortem changes. The use of brain was advantageous because concentration changes are unlikely to
occur in brain tissue due to postmortem redistribution. In these cases the analysis of brain provided further
insight with respect to toxicity by establishing the concentrations of clomipramine and norclomipramine at
the site of action without complications arising from postmortem redistribution.
This communication supplements the database on clomipramine and norclomipramine by providing
quantitative determinations of both parent drug and metabolite in multiple tissues. A literature search
revealed a paucity of data on clomipramine and norclomipramine levels in general and an absence of
documented brain levels. When conducting these postmortem investigations, the inclusion of brain
determinations provided valuable information in assessing the magnitude of toxicity in these cases
involving clomipramine and its active metabolite norclomipramine.
Keywords: clomipramine, postmortem redistribution, tricyclic antidepressants
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