Report of a Fluoxetine Fatality

Kincaid, Rosemary L.; McMullin, Matthew; Crookham, Susan B.; Rieders, Fredric

doi:10.1093/jat/14.5.327

Cited by 55 publications

(15 citation statements)

References 3 publications

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“…The antidepressant study group also reported that tricyclic antidepressant overdoses resulted in more toxicity and more frequent admissions to the intensive care unit than did fluoxetine overdoses [21]. Kincaid et al also reported that very high levels are required for fluoxetine fatality [22].…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

et al. 2007

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Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 mul/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). L: -glutamic acid levels were not affected in all groups. These neurochemical findings show that fluoxetine, a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.

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Section: Discussionmentioning

confidence: 99%

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

et al. 2007

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“…In a retrospective review of data reported to the FDA and TESS, fluoxetine ingestions as low as 100 mg were reported to be associated with seizures and ingestions of as little as 260 mg were reported to be associated with death; however, direct causality by fluoxetine could not be assessed in these cases (29). There were also 11 level 4 or 6 articles with individual case information on acute fluoxetine ingestions in patients 6 years of age and older (57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). Among them, the lowest dose of fluoxetine associated with any toxicity was 80 mg in a 32-year-old woman who developed severe effects but had also ingested other drugs (level 6) (64).…”

Section: Fluoxetinementioning

confidence: 99%

Selective serotonin reuptake inhibitor poisoning: An evidence-based consensus guideline for out-of-hospital management

Nelson

Erdman

Booze

et al. 2007

Clinical Toxicology

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American Association of Poison Control Centers, Washington, District of Columbia, USAA review of US poison center data for 2004 showed over 48,000 exposures to selective serotonin reuptake inhibitors (SSRIs). A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidencebased expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments.The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with a suspected ingestion of an SSRI by 1) describing the process by which an ingestion of an SSRI might be managed, 2) identifying the key decision elements in managing cases of SSRI ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to ingestion of immediate-release forms of SSRIs alone. Co-ingestion of additional substances might require different referral and management recommendations depending on their combined toxicities.This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment.Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in cases in which a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department. This activity should be guided by local poison center procedures. In general, this should occur regardless of the dose reported (Grade D). 2) Any patient already experiencing any symptoms other than mild effects (mild effects include vomiting, somnolence [lightly sedated and arousable with speaking voice or light touch], mydriasis, or diaphoresis) should be transported to an emergency department. Transportation via ambulance should be considered based on the condition of the patient and the length of time it will take the patient to arrive at the emergency department (Grade D). 3) Asymptomatic patients or those with mild effects (defined above) following isolated unintentional acute SSRI ingestions of up to five times an initial adult therapeutic dose (i.e., citalopram 100 mg, escitalopram 50 mg, fluox...

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“…These highly prescribed drugs are, however, frequently used together with other legal or illegal drugs and can result in synergy of symptoms and intoxications [1][2][3][4][5][6][7][8][9][10][11][12]. Furthermore, severe life-threatening interactions such as the serotonin syndrome have been described [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography–mass spectrometry

et al. 2008

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A gas chromatographic-mass spectrometric (GC-MS) method in positive ion chemical ionization mode in combination with a solid phase extraction was optimized for new-generation antidepressants and their metabolites in postmortem blood, brain tissue, and hair. Twelve antidepressants and their active metabolites (i.e., mirtazapine, viloxazine, venlafaxine, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine, desmethylfluoxetine, desmethylmianserin, desmethylmirtazapine, desmethylsertraline, desmethylmaprotiline, desmethylcitalopram, and didesmethylcitalopram) could be quantified. In this article, in addition to the validation of the GC-MS method, four postmortem cases are discussed to demonstrate the usefulness of the described method in forensic toxicology. In these cases, sertraline, fluoxetine, citalopram, and trazodone in combination with their active metabolites were quantified. Blood concentrations ranged from subtherapeutic to toxic concentrations, while brain to plasma ratios ranged from 0.8 to 17. Hair concentrations ranged from 0.4 to 2.5 ng/mg depending on the compound and hair segment.

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Report of a Fluoxetine Fatality

Cited by 55 publications

References 3 publications

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

Selective serotonin reuptake inhibitor poisoning: An evidence-based consensus guideline for out-of-hospital management

Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography–mass spectrometry

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