A case of lacosamide and mirtazapine self-poisoning.

Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 µg/mL and a mirtazapine concentration of 12.0 µg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.

Evidence of repeated mirtazapine poisoning in children by hair analysis.

Mirtazapine is an antidepressant drug, used to treat depression, but also, in some specific conditions, to treat obsessive-compulsive disorder and anxiety. Although mirtazapine is not a hypnotic, it can make the subject feel drowsy. Children under the age of 18 should not take mirtazapine, but for some very special diseases, a physician can prescribe it for a limited period of time. The authors report a case involving 2 children (7- and 9-year-old) who were administered mirtazapine without consent by the mother, who was under daily therapy with this antidepressant. Hair specimens, collected from the children were tested by liquid chromatography coupled to tandem mass spectrometry for mirtazapine and its metabolite, N-desmethylmirtazapine, on 3 × 1 cm segments. The hair test results (3 × 1 cm segments) have demonstrated that both children have been repetitively exposed to mirtazapine for approximately the last 3 months before hair collection, with concentrations in the range 1.32-3.79 and 0.64-2.54 ng/mg for mirtazapine and N-desmethylmirtazapine, respectively. Environmental contamination was ruled out as the measured concentrations are highly variable according to the pattern of drug distribution and the washes were negative. Hair testing for drugs appears as an excellent diagnostic tool for child protection toward drug exposure.

High blood mirtazapine concentration in a newborn - A case of suspected postpartum infanticide.

We report a sudden death of an infant due to mirtazapine poisoning. A 15-day-old newborn boy was found dead when he was sleeping beside his mother who had suffered from panic disorder for approximately 1 year. After giving birth, she complained of palpitations and shaky hands, and was prescribed mirtazapine. The deceased newborn weighed 3,282 g and his height was 55 cm. There were no autopsy findings related to the death. The mirtazapine concentration as quantitated by liquid chromatography-tandem mass spectrometry analysis was 620 ng/mL in right heart blood, and was approximately 10 times higher than the therapeutic level in adults. Because transfer of mirtazapine into breast milk is low, mirtazapine was likely administered intentionally to the newborn. Based on the newborn's immature renal, liver, and blood-brain barrier function, the cause of death was attributed to mirtazapine poisoning. Poison-related homicide in the infant is rare. We report the first case of intentional mirtazapine poisoning case in a newborn.

Bradyarrhythmia due to mirtazapine overdose: A case of serious adverse event in a suicidal patient.

There are a limited number of studies on postoverdose clinical findings of mirtazapine in the literature. Our case presented an unlikely junctional rhythm, which we have not seen in the previous studies, in a patient who had bradycardia and hypotension following mirtazapine intake. A 37-year old male was admitted to the emergency department (ED) after his suicide attempt with 300 mg PO of mirtazapine tablets. He took the drug 2 h prior to his ED visit. He did not have any complaints after the mirtazapine intake. His complete physical examination and electrocardiography (ECG) revealed no pathological findings. He was observed in the ED. The results were in the normal range in his blood test and he has 0 mg/dl of blood ethanol. He experienced dizziness after 5 h and 30 min. The blood pressure was 60/30 mmHg. The heart rate was 34 beats/min. The simultaneous ECG showed junctional bradycardia. 0.5 mg atropine IV was given two times at intervals. Norepinephrine infusion was initiated after normal saline therapy. Forty-five minutes later, he did not have any clinically significant complaint. There are no pathological findings in his follow-up ECG and physical examination. He was discharged of his own accord 10 h after his ED admission. His initial mirtazapine level was 145 ng/ml when he came to the ED. Mirtazapine was known to have a safe cardiac profile both for regular dose and overdose. However, physicians should consider that it might induce a life-threatening bradyarrhythmia.

Cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine treated by percutaneous cardiopulmonary bypass: a case report.

BACKGROUND: Mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants and it is associated with few fatalities. Boric acid is an odorless white powder that is generally not recognized as a poisonous substance. We report a case of cardiac arrest induced by the intentional ingestion of mirtazapine, boric acid, and sennosides, by a patient who required percutaneous cardiopulmonary bypass. CASE PRESENTATION: Our patient was a 49-year-old Japanese woman with a history of depression; she was found in an unconscious state after ingesting boric acid (unknown amount), mirtazapine (1950 mg), and sennosides (780 mg). On arrival, she was in a deep coma with marked hypotension induced by atrial fibrillation, tachycardia, and diffuse hypokinetic cardiac motion. She had systemic diffuse erythema. Her serum concentrations of boric acid and mirtazapine on arrival were 560.49 mg/L and 1270 ng/mL, respectively. She experienced repeated cardiac arrest, and was therefore treated with tracheal intubation, mechanical ventilation, percutaneous cardiopulmonary bypass, and continuous hemodialysis filtration. Stable circulation and respiration and a normal kidney function were finally obtained and she was transferred to a local medical facility in a persistent unconscious state. CONCLUSIONS: This is the first case of a return of spontaneous circulation after cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, requiring percutaneous cardiopulmonary bypass for survival. To maintain cerebral perfusion during percutaneous cardiopulmonary bypass, even in a prolonged state of cardiac arrest induced by overdose, is medically, ethically, and economically challenging.