A fluvoxamine-related fatality: Case report with postmortem concentrations.

Fluvoxamine is a selective serotonin reuptake inhibitor that has been considered relatively safe in overdose. At therapeutic and supratherapeutic concentrations, fluvoxamine affects cardiac conduction, prolongs QTc interval, causes hypotension, obtundation, and can increase propensity for seizures. A man in his 60s was found dead at his home with a postmortem fluvoxamine peripheral blood concentration of 4.9 mg/L, and a liver concentration of 440 mg/kg. His cause of death was determined to be acute fluvoxamine toxicity.

Pediatric ingestion of vilazodone compared to other selective serotonin reuptake inhibitor medications.

BACKGROUND: Unintentional ingestion of selective serotonin reuptake inhibitor (SSRI) medications is common amongst children <6 years of age. Current evidence-based management guidelines are based on a low incidence of significant medical outcomes in these children. OBJECTIVE: To describe and compare outcomes of pediatric exposures to vilazodone with other SSRIs. METHODS: A retrospective observational case series analysis of both single and polysubstance SSRI exposures amongst children <6 years old reported to the National Poison Data System (NPDS). RESULTS: 11,384 SSRI exposures in children <6 years of age reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone only accounted for 5.9% of all exposures, but resulted in the highest proportion of health care facility admission compared to other SSRIs, both in single substance (165 of 531 (31.1%); OR 9.0 [7.3-11.2]) and polysubstance (57 of 107 (53.3%); OR 4.1 [2.7-6.2]) exposures. Children exposed to vilazodone also have higher odds of experiencing a major or moderate outcome in single (134 of 531 (25.2%); OR 20.5 [15.5-27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7-9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such as seizure and coma, were more common among the vilazodone exposures. CONCLUSIONS: Exposure to vilazodone in this age group results in an increased rate of hospitalization as well as more severe clinical effects as compared to other SSRIs. Current evidence-based SSRI exposure management guidelines may not be appropriate for the management of vilazodone ingestion in this age group.

Clinical psychopharmacology and medical malpractice: the four Ds.

The four Ds of medical malpractice are duty, dereliction (negligence or deviation from the standard of care), damages, and direct cause. Each of these four elements must be proved to have been present, based on a preponderance of the evidence, for malpractice to be found. The principles of psychopharmacology and the information in the package insert for a drug often play a central role in deciding whether dereliction and direct cause for damages were or were not applicable in a particular case. The author uses data from two cases in which patients were inadvertently fatally poisoned by medication to illustrate two ways in which such information can affect the outcome. In one case, the clinician should have known that he was giving a toxic dose to the patient, whereas that was not true in the other case.

Status epilepticus following intentional overdose of fluvoxamine: a case report with serum fluvoxamine concentration.

INTRODUCTION: Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is used in the management of depression and obsessive compulsive disorders. We report a patient with status epilepticus requiring quadruple anti-convulsant treatment following a fluvoxamine overdose. CASE REPORT: A 25-year-old female presented with drowsiness at 12 hours following deliberate ingestion of 9.6 grams of fluvoxamine. Sixteen hours after ingestion, she developed status epilepticus that required treatment with benzodiazepines (lorazepam and midazolam), thiopentone, phenytoin and phenobarbitone. Her serum fluvoxamine concentration on presentation was 1970 microg/L (therapeutic 160-220 microg/L) and routine toxicological screening was negative for other drugs. She was discharged home after 72 hours with no further episodes of seizures. DISCUSSION: Most patients with fluvoxamine poisoning are either asymptomatic or may develop mild signs of serotonergic toxicity. Although serotonin syndrome and isolated seizures are reported in fluvoxamine poisoning, we report the first patient with confirmed isolated fluvoxamine toxicity who developed status epilepticus.

[A case of fluvoxamine overdose].

Selective serotonin reuptake inhibitors (SSRI) are newly developed-antidepressants authorized in 1999 in Japan. We experienced a case of drug poisoning including fluvoxamine, one of SSRI. A comatose nineteen-year-old girl was transported to our ER in the morning on July 25, 2000. There remained many empty packages of fluvoxamine and several sorts of tranquilizers in the room. Her consciousness became alert over the next morning. HPLC analysis revealed fluvoxamine, chlorpromazine, promethazine, biperiden, phenobarbital, and zopiclone in her blood and that serum concentrations of the first three were above the therapeutic ranges. The peak values of fluvoxamine, chlorpromazine, and promethazine were 1,343 ng/ml (6.7 times of the upper limit), 861 ng/ml (2 times), and 529 ng/ml (1.3 times), respectively. Fluvoxamine must be a main cause of her toxic symptoms although other CNS-depressing drugs might work jointly.

Aminophylline reversal of antihypertensive agent toxicity.

Hypotension occurred following a combined beta blocker (atenolol), angiotensin converting enzyme inhibitor (quinapil) and selective serotonin reuptake inhibitor (fluvoxamine) overdose. In another instance heart block and hypotension was noted in association with a diltiazem and atenolol adverse interaction. Crystalloid infusion was ineffective in both cases, but toxicity was rapidly reversed with aminophylline administration. Aminophylline's recognized inotropic and chronotropic properties make it a potentially valuable therapeutic agent in the treatment of antihypertensive medication toxicity.

Phenytoin intoxication induced by fluvoxamine.

A patient had phenytoin intoxication after administration of fluvoxamine, a selective serotonin reuptake inhibitor. The serum concentration of phenytoin increased dramatically from 16.6 to 49.1 microg/mL when fluvoxamine was coadministered, although the daily dosage of phenytoin and other drugs had not changed. During phenytoin and fluvoxamine treatment, ataxia, a typical side effect of phenytoin, was observed. The genotypes of CYP2C9 and 2C19, the enzymes responsible for phenytoin metabolism, were homozygous for the wild-type alleles (CYP2C9*1/*1 and 2C19*1/ *1). The interaction may be a result of inhibition of both CYP2C9 and 2C19 by fluvoxamine.

Fluvoxamine distribution in postmortem cases.

Four postmortem cases are reported in which the selective serotonin re-uptake inhibitor fluvoxamine was identified. Fluvoxamine was detectable using a standard alkaline drug screen, chromatographed well using a HP-1 column, and did not require derivitization for quantitation. Two of the cases reported were drug intoxications; fluvoxamine was only an incidental finding in the other 2 cases. Central and peripheral blood values are reported, as well as antemortem blood, bile, vitreous fluid, and urine values. No solid organs were obtained in any of the cases. Quantitations were performed using both an analytical standard and a fluvoxamine tablet for the preparation of calibrators. A comparison of quantitative values was made to evaluate the feasibility of using a tablet as the drug source for the preparation of calibrators when a pure reference material is unavailable. Postmortem peripheral blood concentrations ranged from approximately 0.5 mg/L in a case of suicidal shooting to approximately 6 mg/L in a case of drug overdose. Evidence of postmortem redistribution was noted in the only case for which both central and peripheral blood were obtained. Quantitations using an extracted drug tablet for the preparation of calibrators correlated well with quantitations using a pure reference material.

SSRI safety in overdose.

BACKGROUND: The morbidity and mortality caused by tricyclic antidepressant (TCA) overdose are well recognized. Among newer antidepressants, the selective serotonin reuptake inhibitors (SSRIs) are thought to be safer in overdose. This study was designed to describe the signs, symptoms, and mortality associated with SSRI overdose. METHOD: English-language articles identified through MEDLINE (1985 through 1997), and case reports from the American Association of Poison Control Centers (AAPCC) (1987 through 1996) and United States Food and Drug Administration (FDA) adverse event database (through 1997) that describe findings of fatal and nonfatal overdoses involving SSRIs alone or in combination with other ingestants were reviewed. RESULTS: SSRI antidepressants are rarely fatal in overdose when taken alone. During the 10 years that SSRI antidepressants have been marketed, there have been remarkably few fatal overdoses reported in the literature or to the AAPCC or FDA involving ingestion only of an SSRI. Moderate overdoses (up to 30 times the common daily dose) are associated with minor or no symptoms, while ingestions of greater amounts typically result in drowsiness, tremor, nausea, and vomiting. At very high doses (> 75 times the common daily dose), more serious adverse events, including seizures, electrocardiogram (ECG) changes, and decreased consciousness may occur. SSRI overdoses in combination with alcohol or other drugs are associated with increased toxicity, and almost all fatalities involving SSRIs have involved coingestion of other substances. CONCLUSION: The SSRI antidepressants are far safer than the TCAs in overdose. There is no apparent difference among SSRIs with respect to overdose safety.

Acute fluvoxamine poisoning.

A total of 221 cases of deliberate acute overdose with fluvoxamine reported to the Paris Poison Centre, and 78 cases collected by the International Drug Safety Department of Duphar BV were analysed. Other agents, mainly benzodiazepines, neuroleptics, other antidepressants and alcohol, were also taken in 77% of the cases. The acute toxicity that could be attributed to fluvoxamine alone was rarely severe. The symptoms observed were always benign when the dose of fluvoxamine was below 1000 mg and included drowsiness, tremor, nausea, vomiting, abdominal pain, bradycardia and/or anticholinergic effects (dry mouth, mydriasis, sinus tachycardia, urinary retention). Seizures occurred in a few cases after high doses (generally > 1500 mg). Cardiotoxicity was not a serious problem; sinus bradycardia was noted with doses of less than 1000 mg, but was always moderate and required no treatment. Conduction abnormalities were rare.

Overdose and safety with fluvoxamine.

The large number of antidepressants available provides a wide range of choice. While clinical effectiveness is the most important consideration, toxicity in overdose must be considered in the risk-benefit assessment of each antidepressant. There are almost 300 deaths each year in Britain from tricyclic overdose, and very few deaths from newer antidepressants. Fluvoxamine appears to have low toxicity in overdose. Symptoms are often minimal: nausea, vomiting, dizziness and somnolence. There is one reported case of prolonged cerebral depression after ingestion of 5.5 g. Overdoses of up to 9 g have produced minimal symptoms and full recovery. No deaths from overdose with fluvoxamine alone have been reported in the literature, although one death certificate in Britain has mentioned fluvoxamine as the cause of death. Fluvoxamine appears to be a valuable alternative to the tricyclic antidepressants, and has a high margin of safety in overdose.