2 fatal polyintoxication cases involving citalopram

Salle, Sophie, Roussel, Olivier and Carlin, Michelle (2015) 2 fatal polyintoxication cases involving citalopram. In: TIAFT 2015 - 53rd Annual Meeting of The International Association of Forensic Toxicologists, 30 August - 4 September 2015, Florence.

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Abstract

Citalopram is a selective serotonin reuptake inhibitor (SSRI) class of antidepressants prescribed to treat severe
depression and treat anxiety. Marketed in many countries, it is easily available to the French population, known to
be one of the biggest consumers of antidepressants in Europe. Although citalopram overdose has long been known
to cause cardiotoxicity especially QT prolongation and torsades de pointes, seizures and serotoninergic syndrome,
only a few reports have analysed citalopram levels in post mortem blood.

We report two fatal cases involving citalopram: a 47 year old woman and a 55 year old man. Both treated for
severe depression, were discovered dead in what was believed to be a case of suicide. Toxicological screening was
performed to assist in establishing the cause of death.
Blood alcohol was determined using GC-FID (Thermo Scientific). When screening for organic xenobiotics, preparation
consisted of liquid-liquid extraction of 1 mL of blood collected with sodium fluoride preservative at both acid
and alkaline pH by ternary solvent (dichloromethane/hexane/ethyl acetate, 50/40/10, v/v/v). After evaporation, the
dry residue was reconstituted in mobile phase at initial condition. The first half of the sample was directly analysed
by LC-MS and DAD (Agilent 1100-MSD). Separation was performed on a Macherey-Nagel Nucleodur C18 Gravity
column (150 mm x 2 mm, 3 µm) with a mobile phase gradient at 0.5 mL/min (methanol / water 5 mM ammonium
formate with 0.2% formic acid). For the second part, after evaporation to dryness and acetylation, analysis was
performed on full-scan mode with a GC-MS (Thermo Scientific) equipped with a Varian CP-Sil 8 CB Low Bleed/MS
column (25 m × 0.25 mm × 0.25 µm). All substances found were subsequently quantified by LC-MS after addition
of internal standard.

In both cases, high blood concentration of citalopram was found (5.54 and 0.93 mg/L respectively) related to its
main metabolite desmethylcitalopram (0.19 and 0.17 mg/L respectively). Citalopram was associated with various
other psychoactive substances. In the first case, a toxic level of alimemazine (0.77 mg/L) was discovered as well
as a therapeutic level of zolpidem (0.16 mg/L), nordazepam (0.53 mg/L) and cyamemazine (0.35 mg/L with 0.86
mg/L of norcyamemazine). In the second case, a high blood alcohol level was also found (3.53 ± 0.17 g/L) alongside
various analgesics within therapeutic ranges (dextropropoxyphene, paracetamol and tramadol at 0.27, 3.7 and 0.6
mg/L respectively).
Considering both cases, citalopram was identified within the toxic range (over 0.5 mg/L).

Numerous CYP enzymes
are involved in citalopram metabolism especially CYP2D6, CYP3A4 and CYP2C19. Use of citalopram with CYP2C19
inhibitors is not recommended by the FDA. Based on this recommendation, no significant pharmacokinetic drug
interactions were found among citalopram and the other drugs reported. In those cases, the metabolizer status
was not investigated. The overdose of citalopram appears to be responsible for the death, even though presence of
other drugs may have potentiated its toxic effects.

Item Type:	Conference or Workshop Item (Poster)
Subjects:	B200 Pharmacology, Toxicology and Pharmacy F400 Forensic and Archaeological Science
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Michelle Carlin
Date Deposited:	12 Jan 2016 13:50
Last Modified:	12 Oct 2019 18:30
URI:	http://nrl.northumbria.ac.uk/id/eprint/25372

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