Fatal overdose with a combination of SNRIs venlafaxine and duloxetine.

Drugs for the treatment of depressive disorders, including SNRIs (serotonin noradrenaline reuptake inhibitors) venlafaxine and duloxetine, are widely prescribed as they have a high therapeutic to toxicity ratio. In rare cases, adverse effects may be severe, usually due to iatrogenic, accidental or intentional self-overdose that cause the excessive accumulation of serotonin and noradrenaline in synaptic clefts. Lethal intoxication with a combination of venlafaxine and duloxetine (postmortem blood concentrations 24 mg/L and 0.97 mg/L, respectively) without co-ingested substances, comorbidities or injuries that could have an unknown contribution to a fatal outcome is presented for the first time in the following case report, with a comprehensive clinical history, and complete results of the performed analyses. The cause of death was a serotonin syndrome that progressed to death in approximately six hours and 15 min after the suicidal ingestion of venlafaxine and duloxetine. Despite the high therapeutic to toxicity ratio SNRIs, which are reserved for patients with severe forms of depressive disorders and a higher suicidal tendency, they should be cautiously prescribed and handed over in smaller packages to make them easier to follow, and thus avoid accumulation within the patient's reach.

Venlafaxine intoxication with development of takotsubo cardiomyopathy: successful use of extracorporeal life support, intravenous lipid emulsion and CytoSorb®.

We describe a young patient who ingested 18 g (240 times the daily therapeutic dose) of venlafaxine in a suicide attempt. She developed severe cardiomyopathy in a takotsubo distribution causing cardiogenic shock and multi-organ dysfunction syndrome (MODS). She was successfully treated with intravenous lipid emulsion (ILE), extracorporeal life support (ECLS) and CytoSorb®. This is remarkable as, to the best of the authors' knowledge, this is the highest amount of venlafaxine intake seen in the literature with a nonfatal outcome.

Comparative Resuscitative Methods for Venlafaxine Toxicity in a Swine Model.

OBJECTIVES: Venlafaxine overdose can lead to cardiovascular collapse that is difficult to resuscitate with traditional Advanced Cardiovascular Life Support protocols. Evidence has suggested that lipid emulsion infusion therapy has been successful in the treatment of antidepressant overdose. No studies have determined the optimal combination of lipid/advanced cardiovascular life support therapy for treatment. METHODS: This study was a prospective, experimental, between subjects design with a swine model investigating the effectiveness of drug combinations administered with cardiopulmonary resuscitation (CPR) postvenlafexine overdose. Subjects were randomly assigned to 1 of eight groups containing seven subjects. The groups tested were CPR only and CPR with epinephrine alone; vasopressin alone; lipid alone; epinephrine and vasopressin; epinephrine and lipid; vasopressin and lipid; and epinephrine, vasopressin, and lipid. The outcomes of interest were survival odds and time to return of spontaneous circulation. RESULTS: Results on these swine models indicate that the use of vasopressin coupled with lipids for venlafaxine overdose resulted in a higher survival rate when compared to the control group (p = 0.023). Groups receiving vasopressin experienced statistically faster times to return of spontaneous circulation than other groups (p = 0.019). CONCLUSIONS: The results suggest that in swine models, the optimal treatment for venlafaxine overdose would include vasopressin with lipids.

Successful use of therapeutic hypothermia after cardiac arrest due to amitriptyline and venlafaxine intoxication.

The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of depression, but possess significant cardiotoxicity, and are one of the most common medications used in suicide attempts worldwide. TCA poisoning can cause hypotension, seizures, and cardiac conduction disturbances, which can lead to life-threatening arrhythmia. Current guidelines recommend mild therapeutic hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment itself can cause disturbances in cardiac conduction, which could aggravate the effect of TCAs on cardiac conduction. We report the successful use of TH in a 19-year-old woman who was resuscitated from ventricular tachycardia after intentional ingestion of amitriptyline and venlafaxine, a serotonin-norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm was ventricular tachycardia with no detectable pulse. Three defibrillations, magnesium sulfate, and sodium bicarbonate were given and her trachea was intubated, after which return of spontaneous circulation (ROSC) was achieved in 26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of-hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of norepinephrine was initiated for low blood pressure. On arrival at the university hospital, she was unconscious and had dilated pupils. She was tachycardic with a body temperature of 33.5°C. She was transferred to the intensive care unit and TH was maintained with invasive cooling. During the TH treatment, she did not experience any serious cardiac arrhythmia, transthoracic echocardiogram was normal, and the electrocardiogram (ECG) returned to normal. The patient was extubated 45 hours after the cardiac arrest. After the extubation, she was alert and cooperative, but slightly delusional. She was transferred to a ward on the third day and discharged from hospital on the sixth day of admission. Ambulatory psychiatric follow-up was organized. Neuropsychological examinations were later performed and she was estimated to be able to work at her previous job. This case report suggests that mild TH is safe even in case of intoxication with a drug known to cause serious cardiac conduction disturbances and arrhythmia.

[Fatal outcome after overdosage with antidepressants]. / Fatalt forløb efter overdosering med serotonin- og noradrenalingenoptagelseshæmmere.

Serotonin syndrome (SS) is a complication after overdosage with antidepressants. SS increases the level of circulating serotonin. Fatal outcome of SS is most often seen in cases where there has been an overdosage with selective serotonin reuptake inhibitors (SSRI)/selective noradrenaline reuptake inhibitors (SNRI) in combination with other serotonin increasing drugs. This case report describes the rapid development of symptoms in a 54-year-old man who ingested a total amount of 6.5 g of SSRI and SNRI drugs as the only drug types. It proves the importance of being aware of the symptoms of SS when the patient is first seen in the emergency department.