Patterns of toxicity and factors influencing severity in acute adult trimipramine poisoning.

AIMS: To analyze the clinical features of trimipramine poisoning, identify a minimal toxic dose, and the dose bearing a 50% risk of developing a moderate, severe or fatal outcome. METHODS: All acute adult trimipramine monointoxications reported by physicians to the Swiss Toxicological Information Centre between January 1992 and December 2009 were identified. RESULTS: Two hundred and thirty cases (26 confirmed and 204 probable) were analyzed, the mean age was 35.7 years and 74% were females. One hundred and thirty-seven patients showed mild, 54 moderate and 21 severe symptoms. Three cases were fatal due to refractory cardiovascular collapse. Ninety-three per cent of the events were attempted or completed suicides. The most common symptoms were central nervous system depression (79.2%), tachycardia (19.1%) and QT(c) prolongation (13.9%). The severity of poisoning depended significantly on the ingested dose (P < 0.001). The minimal dose for moderate symptoms was 250 mg (median dose 1.2 g) and 850 mg for severe symptoms (median dose 2.7 g). The dose for a 50% risk of developing a moderate, severe or fatal outcome was 5.11 g. In 38 patients early gastrointestinal decontamination was performed. Overall, these patients ingested higher trimipramine doses than the late- or not-decontaminated patients (P = 0.113). The median doses were also higher in the decontaminated group within each severity category except in the fatal cases. CONCLUSIONS: We demonstrated that moderate trimipramine poisoning can already occur after ingestion of doses in the high therapeutic range. Poisoned patients have to be monitored for central nervous system depression, dysrhythmias and QT(c) prolongation. Early decontamination might be beneficial.

Radiopaque stomach contents in postmortem CT in suicidal oral medication intoxication: report of three cases.

In clinical medicine, plane radiography is used for detecting the remains of medications in the stomach in oral medication intoxication cases. Since postmortem computed tomography (CT), performed prior to autopsy, is currently intensively entering the forensic routine, the technique was applied to three fatal cases of oral medication intoxication. Here we report CT and autopsy findings for these cases. In all three cases, hyperdense areas within the stomach content were documented. The measurement of Hounsfield Units (HU) beyond 74HU showed mean values of 338, 88 and 98HU. Postmortem CT also showed brain edema and pulmonary aspiration in one case. At autopsy, tablet remains in the stomach were detected microscopically in all three cases. The ex vivo CT scans of the ingested medicaments showed similar HU values. Despite the fact that further case studies are necessary beyond this one, and in spite of its limitations, postmortem CT was found to be a useful screening and documentation method for stomach contents in oral medication intoxication.

[Hypotensive cardio-circulatory failure and metabolic acidosis after suicidal intoxication with trimipramine and quetiapine. Case report and background]. / Hypotones Kreislaufversagen und metabolische Azidose nach suizidaler Mischintoxikation mit Trimipramin und Quetiapin. Fallbericht und Hintergrund.

The case of a 44-year-old female patient is reported, who ingested trimipramine and quetiapine in a suicide attempt. Initially sinus tachycardia and hypotension were seen, which resulted in a hypotensive cardio-circulatory failure despite fluid therapy and administration of catecholamines. Because of the life-threatening situation and the fact that the ingestion was 2 h prior to admission, a rapid transport to the next hospital was preferred to treatment with active charcoal. Intoxication with tricyclic antidepressants are very common in Europe and have a mortality of up to 15% in severe cases. The specific therapy consists of airway management, hemodynamic stabilization and primary elimination of the poison. Secondary detoxication is less important. The administration of the antidote physostigmine is controversial but carbo medicinalis should be given orally or via a gastric tube.

Fatality caused by a combined trimipramine-citalopram intoxication.

A 53-year-old woman who was diagnosed as suffering from depression was found dead in her bed. The autopsy revealed no morphological changes sufficient to explain death. Toxicological analysis was performed and the drugs trimipramine (2.33 mg/l), citalopram (4.81 mg/l) and zolpidem (0.07 mg/l) were identified in the femoral blood. A combined drug intoxication resulting in synergistic effects to cardiovascular disorders was proposed as the cause of death. An acute overdose and suicide was suggested by calculation of the parent drug to main metabolite ratios in femoral blood and liver tissue. The trimipramine to desmethyltrimipramine ratios were calculated to be 2.06 and 3.18, the citalopram to desmethylcitalopram ratios were 1.96 and 2.02.

Post-mortem toxico-kinetics of trazodone.

Trazodone is a structurally unique bicyclic anti-depressant, said to be significantly less toxic than other anti-depressants following an acute overdose. We studied the tissue distribution and post-mortem redistribution of trazodone in two fatalities, one of which allowed comparison with trimipramine, a typical tricyclic anti-depressant. Case 1, a 53-year-old female weighing 72 kg, had femoral vein concentrations of trimipramine 5.5 micrograms/ml, trazodone 14.4 micrograms/ml and alcohol 107 mg%. Case 2, a 48-year-old female of 70 kg, had a femoral vein trazodone of 15.5 micrograms/ml and alcohol 34 mg%, with no other drugs detected. For case 1 and case 2 respectively, trazodone tissue concentrations were: skeletal muscle 7.3 and 9.0 micrograms/g; left and right lungs 13.3, 12.9 and 35.3, 40.1; myocardium, 30.9 and 28.9; kidneys 34.7 and 39.6; liver 73.7 and 82.4; fat 18.5 and 16.5; brain 48.6 and 20.9. For case 1 and 2, respectively, blood trazodone concentrations in 10 initial autopsy samples ranged from 13.7-17.3 and 14.4-16.9 micrograms/ml. Twenty-four and forty-eight hours later the respective ranges were 12.8-18.0 and 12.4-19.9 for case 1, 12.5-20.1 and 12.7-27.0 for case 2. By contrast, for trimipramine, blood concentrations at 0 time, 24 h and 48 hours ranged from 5.5-11.4, 5.2-14.3, and 4.2-18.2, respectively. We conclude that trazodone shows little preferential concentration in solid organs and consequently has relatively stable post-mortem blood concentrations with little drug redistribution artefact. Both the clinical pharmacokinetics and post-mortem toxicokinetics of trazodone differ significantly from the tricyclic anti-depressants.

[Suicide with chloroquine combined with maprotiline and trimipramine]. / Suizid mit Chloroquin unter Beteiligung von Maprotilin und Trimipramin.

Report on suicide with chloroquine in combination with maprotiline and trimipramine. Chloroquine and his metabolite monodesethylchloroquine could be determined in organs and body fluids. The highest organ-concentrations of chloroquine were found in liver and kidney. The survival time and dose are discussed.

Fatal seizures associated with trimipramine poisoning.

The present report describes a witnessed, fatal attack of seizures. Very high levels of trimipramine were found in the blood collected at autopsy. The cause of death would most likely have been misinterpreted as a suicidal intoxication if the attack had not been witnessed. Conversely, if toxicologic examination had not been undertaken, the fatality would probably have been registered as epilepsia.

Distribution of trimipramine and its major metabolites in a fatal overdose case.

A fatality following ingestion of the tricyclic antidepressant trimipramine (Surmontil) is described. Quantitation was performed by high-performance liquid chromatography. Trimipramine and desmethyltrimipramine concentrations were 4.8 and 2.1 mg/L, respectively, in postmortem blood. The concentration of trimipramine, desmethyltrimipramine, and their respective 2-hydroxy metabolites were also measured in liver and urine. Analysis of gastric contents revealed a tricyclic antidepressant drug. These findings are compared to previously published reports of trimipramine-related fatalities.

Toxicological findings in a death resulting from the ingestion of trimipramine.

A fatality following ingestion of the tricyclic antidepressant trimipramine is presented. Whole blood concentrations of trimipramine and its metabolite N-desmethyltrimipramine were measured by gas-liquid chromatography and found to be 400 and 1130 ng/mL, respectively. These findings are compared to those of previous unpublished trimipramine fatalities and fatalities caused by other tricyclic antidepressants.

Survival following massive overdose of adrenergic blocking agents (acebutolol and labetalol).

Massive overdosage of adrenergic blocking drugs is associated with severe morbidity and a high mortality rate. We report the case of a 24-year-old medical intern who ingested 9.6 g acebutolol, 7.2 g labetalol and 0.625 g trimipramine in an attempted suicide. Blood samples drawn on admission were shown to contain markedly elevated plasma levels of acebutolol and its major metabolite and of labetalol. The patient was deeply comatose on admission. The heart rate was 60 min-1 (sinus rhythm) and the blood pressure was clinically unrecordable. Atropine, isoproterenol and dopamine initially had no effect on either heart rate or blood pressure. Only following the administration of inordinately large doses of isoproterenol and dopamine, together with glucagon was a clinical response obtained. The patient remained haemodynamically dependent on dopamine for 12 h and isoproterenol for 65 h. The total dose of isoproterenol administered was 260 mg, two thirds of this during the first 12 h. The patient left hospital well after 7 days but was readmitted after 26 days because of intestinal obstruction due to ischemic bowel necrosis.

Analysis of blood and tissue for amoxapine and trimipramine.

A method for the identification and quantitation of two tricyclic antidepressants, amoxapine (Asendin) and trimipramine (Surmontil) is presented here. Samples were extracted with hexane at pH 10, back-extracted with 1.0N sulfuric acid. The acidic layer was adjusted to pH 10 and re-extracted with hexane. Electron impact mass spectra were obtained. The base peak and molecular ion for amoxapine were at m/z 245 and 313, respectively. The base peak and molecular ion for trimipramine were at m/z 58 and 294, respectively. There were three forensic toxicology cases involving amoxapine in Cook County, IL, in 1980 and 1981. The concentrations of amoxapine in blood for these three cases were 1.66 mg/L, 7.16 mg/L, and 2.95 mg/L, respectively.