Case report
Suicidal overdose with relapsing clomipramine concentrations due to a large gastric pharmacobezoar

https://doi.org/10.1016/j.forsciint.2013.03.025Get rights and content

Abstract

The paper presents a case of fatal intoxication after massive sustained-release clomipramine overdosage with prolonged toxicity related to a large gastric pharmacobezoar. 42-year-old female was admitted to the toxicology unit 14 h after drugs ingestion. At admission patient was deeply unconscious, required controlled mechanical ventilation. Serum total level of TCAs was 1955 ng/mL. Gastric lavage revealed no pills. Within the next 12 h the patient's clinical condition improved. TCAs level decreased to 999 ng/mL. However, after another 10 h the clinical condition started deteriorating again and the patient went into a deep coma requiring controlled mechanical ventilation. TCAs level increased to 2011 ng/mL. X-ray and computed tomography revealed large pharmacobezoar consisted from radio-opaque pills. In the 28th h of hospitalization gastrotomy was performed, confirming presence of pharmacobezoar formed from Anafranil SR tablets. After surgery TCAs level was gradually decreasing. However, the patient's condition did not improve, she died 32 h after gastrotomy. Post-mortem analyses revealed drug and its metabolite toxic levels in blood (clomipramine – 1729 ng/mL, norclomipramine – 431 ng/mL) and toxic levels in internal organs: myocardium (clomipramine – 14,420 ng/g, norclomipramine – 35,930 ng/g), vitreous humor (clomipramine – 1000 ng/mL, norclomipramine – 3110 ng/mL).

Described case report indicates that sustained release clomipramine tablets may form pharmacobezoar. X-ray and computed tomography examinations should be considered in cases of massive abuse of sustained release clomipramine, particularly if symptoms of intoxication are recurrent or persistent.

Introduction

Pharmacobezoars are concretions of pharmaceutical products that form and persist in the gastrointestinal tract [1]. Pharmacobezoars may form from various oral forms of drugs, both as a result of acute overdose and during chronic use of therapeutic doses [1], [2], [3], [4], [5], [6], [7], [8], [9]. Formation of pharmacobezoars is possible especially following massive abuse of sustained release tablets or capsules [5], [9], [10], [11], [12]. In those cases an active substance may be released from pharmacobezoars causing persistent or recurrent intoxication [9], [10], [13], [14], [15], [16].

Diagnosis of pharmacobezoars trapped in gastrointestinal tract is highly difficult. Pharmacobezoars have solid form and standard gastric lavage may reveal no pills in returning fluids. X-ray or computed tomography is not routinely performed in intoxicated patients. Moreover, most pharmaceutical products are not radio-opaque and plain X-ray may reveal no pathological shadows. The presence of pharmacobezoar in gastrointestinal tract should be suspected in cases of prolonged or recurrent intoxication.

Clomipramine is a dibenzazepine tricyclic antidepressants widely used in the treatment of depression, obsessive-compulsive disorders and phobias.

The paper presents a case of acute intoxication after massive doxepin and sustained-release clomipramine overdosage with relapsed toxic serum concentration of tricyclic antidepressants (TCAs) related to a large gastric pharmacobezoar. The intoxication was fatal despite surgical removal of the pharmacobezoar.

Section snippets

Case report

A 42-year-old female, with a 2-year history of depression, was admitted to the toxicological unit because of TCAs abuse with a suicidal intent. A letter found by ambulance staff in the patient pocket indicated that 14 h earlier she had ingested 60 tablets of Anafranil SR (75 mg clomipramine per tablet) and 30 capsules of doxepin (25 mg doxepin per capsule). At admission the patient was deeply unconscious with a Glasgow Coma Scale score (GCS) of 5. Arterial blood pressure (BP) was 90/50 mmHg and

Materials

Ethyl acetate (Sigma, Taufkirchen, Germany) was HPLC grade. Doxepin, clomipramine and N-desmethylclomipramine were purchased from Lipomed AG (Arlesheim, Switzerland). Biological samples of blood collected from femoral vein, eye vitreous, myocardium, brain and liver were obtained during autopsy and stored in −20 °C.

Sample preparation

Tissue sample (0.2 g) were homogenized and digested using 5 mL 0.1 N NaOH solution in 37 °C overnight. Aliquots of biological samples (1 mL each), were brought to pH 9 using 1 N HCl and 1 mL

Results

Post mortem examination revealed cerebral and pulmonary edema, passive hyperaemia of internal organs and shock kidneys. Post-mortem concentrations of doxepin, clomipramine and its main metabolite – norclomipramine in blood and internal organs was determined with gas chromatography with mass spectrometry (Table 1).

Discussion

In presented case the patient was admitted to Toxicology Unit 14 h after a suicidal abuse of TCAs. However, considering the information that there is a sustained-release preparation among the taken drugs, gastric lavage was performed. Moreover, repeated doses of activated charcoal and polyethylene glycols were used for decontamination of the gastrointestinal tract. Unfortunately, the applied methods of the gastrointestinal decontamination proved completely unsuccessful and failed to prevent

Funding

This research received no specific grant from any funding agency in the public, commercial, or not for-profit sectors.

References (17)

There are more references available in the full text version of this article.

Cited by (16)

  • Study of the distribution of antidepressant drugs in vitreous humor using a validated GC/MS method

    2020, Forensic Science International
    Citation Excerpt :

    Several chromatographic methods for the determination of ADs in different biological materials have been published, but only a few were applied in VH. These methods use different instrumentation, such as GC coupled to MS [14,19–21] or tandem MS/MS [22], as well as LC coupled to several detectors, i.e. MS/MS [23,24] and QTOF [25]. There is only one published method for the determination of a significant number of drugs in VH, that includes 9 ADs and metabolites [14], while most of the studies are focusing on a single [19,22,24,26,27] or two analytes [20] and their metabolites [23,28].

  • Management of an overdose patient

    2020, Toxicology Cases for the Clinical and Forensic Laboratory
  • Paediatric pharmacobezoar in vitamin overdose

    2017, Cirugia y Cirujanos (English Edition)
View all citing articles on Scopus
View full text