desvenlafaxine-succinate and Drug-Overdose

Desvenlafaxine is used to treat major depression. Desvenlafaxine is also the active metabolite of venlafaxine. Venlafaxine overdose can cause serotonin toxicity, seizures and cardiovascular effects, but there is limited information on desvenlafaxine overdose.. We aimed at investigating the clinical effects and complications from desvenlafaxine overdose.. This was a retrospective observational study of desvenlafaxine overdoses over a six-year period. Demographic details, dose and timing of the overdose, together with clinical effects, treatment and complications were extracted from a local hospital network database or the medical records of patients following hospital admission with a desvenlafaxine overdose.. There were 182 cases of desvenlafaxine overdose included in the study. From the 182 cases, 75 were desvenlafaxine (± alcohol) only ingestions and 107 included one or more co-ingested drugs. In single-agent desvenlafaxine ingestions, median age was 25 years (range: 13-68 years) with a median ingested dose of 800 mg (range: 250-3500 mg; interquartile range (IQR): 600-1400 mg), and 54/75 (72%) were female. The Glasgow Coma Score (GCS) was 15 in 68/74 (92%) patients, 13-14 in 5/74 (7%), and was seven in one patient following aspiration. Mild hypertension (systolic blood pressure [BP] > 140-180 mmHg) occurred in 23/71 patients (32%), and tachycardia occurred in 29/74 (39%) patients. There were no abnormal QT intervals and no QRS >120 m s. Serotonin toxicity was diagnosed by the treating physician in 7/75 (9%) patients, but only one of these met the Hunter Serotonin Toxicity Criteria. None of the 75 patients who took desvenlafaxine only (± alcohol) had seizures, were admitted to intensive care or died. In comparison, the 107 patients taking desvenlafaxine in overdose with other medications developed more pronounced toxicity. Generalised seizures occurred in 5/107 (5%), but in three of these cases co-ingestants were possible proconvulsants. Fifteen patients had a GCS ≤9 and none had an abnormal QT or QRS. Severe effects appeared to be associated with coingestants.. Desvenlafaxine overdose causes minor effects with mild hypertension and tachycardia. The risk of seizures or serotonin toxicity is low.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Desvenlafaxine Succinate; Drug Overdose; Female; Glasgow Coma Scale; Humans; Hypertension; Male; Middle Aged; Retrospective Studies; Seizures; Tachycardia; Young Adult

Topics: Adolescent; Amitriptyline; Antidepressive Agents, Tricyclic; Consciousness; Depression; Desvenlafaxine Succinate; Drug Overdose; Drug Therapy, Combination; Electrocardiography; Emergency Service, Hospital; Female; Glasgow Coma Scale; Humans; Hypotension; Long QT Syndrome; Seizures; Serotonin and Noradrenaline Reuptake Inhibitors

Tako-Tsubo cardiomyopathy (TTC) occurs particularly in post-menopausal women, being precipitated in many cases by severe emotional stress. We describe six patients in whom TTC occurred in association with therapeutic ingestion or overdose of the serotonin/noradrenaline reuptake inhibitor venlafaxine, or its metabolite desvenlafaxine. Importantly, two of the six cases were not post-menopausal women. An increased risk of TTC may account for some of the reported cardiovascular adverse effects of venlafaxine and similar agents.

Topics: Adult; Aged; Aged, 80 and over; Cyclohexanols; Desvenlafaxine Succinate; Drug Overdose; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Normetanephrine; Peptide Fragments; Selective Serotonin Reuptake Inhibitors; Takotsubo Cardiomyopathy; Venlafaxine Hydrochloride

Venlafaxine (VEN) is a serotonin-norepinephrine-dopamine reuptake inhibitor that causes usually a mild cardiotoxicity when ingested in overdose. We report a patient who developed acute heart failure following overdose. As the toxicokinetic data suggested a prolonged metabolism, genetic polymorphisms for cytochrome P450 isoenzymes CYP2D6 and CYP2C19 were also investigated.. A 34-year-old woman was admitted to the hospital 10 hours after the ingestion of an 11.25 g overdose of VEN. She was comatose and suffered two self-limited seizures. The electrocardiogram showed diffuse ST segment depression, but normal QRS and QTc duration. The plasma levels on admission were 18,015 and 3,846 ng/ml for VEN and the metabolite O-desmethylvenlafaxine (ODV), respectively. The patient developed severe cardiodepression. The left ventricular shortening fraction was only 9% on echocardiography. The patient was oliguric and required continuous venovenous hemofiltration. The administration of milrinone was required for 12 days, and norepinephrine for 10 days. Left ventricular function recovered. The calculated elimination half-life was 30.8 and 72.2 hours for VEN and ODV, respectively. The patient genotype was CYP2D6*1/*5, the *5 allele corresponding to a complete deletion of CYP2D6 gene.. Severe and sustained cardiotoxicity following VEN overdose may be related to the amount ingested, as well as to the genetic polymorphism for CYP2D6 leading to a delayed elimination of active metabolite.

Topics: Adult; Aryl Hydrocarbon Hydroxylases; Cardiomyopathies; Cyclohexanols; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Desvenlafaxine Succinate; Drug Overdose; Female; Gene Deletion; Half-Life; Heart Failure; Humans; Milrinone; Norepinephrine; Polymorphism, Genetic; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride