Serum fluoxetine and norfluoxetine levels support the safety of fluoxetine in overdose

Annals of General Psychiatry, Nov 2016

Background Previous literature has found fluoxetine to be relatively safe in overdose. This study hopes to examine this idea along with support from published pharmacokinetic information including serum fluoxetine and norfluoxetine levels based on information from a clinical case series. Methods Four cases are presented along with vital abnormalities, electrocardiogram abnormalities, and physical exam abnormalities along with amount of overdose and resulting serum fluoxetine and norfluoxetine levels. Case Presentation In these four cases, serum fluoxetine and norfluoxetine days after overdose were found to be in a range believed to be within the treatment range. No abnormalities were found on electrocardiogram but some patients (3) were found to have slight elevations in heart rate. Conclusion Fluoxetine is relatively safe in overdose. This study supports previous literature. Future directives for research can be directed towards when serotonergic, including fluoxetine, medications can be introduced or restarted in patients who have overdosed. Research could also focus on if the introduction of another medication, such as carbamazepine, to induce metabolism of a medication, such as fluoxetine, after an overdose.

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Serum fluoxetine and norfluoxetine levels support the safety of fluoxetine in overdose

Pope and Zaraa Ann Gen Psychiatry Serum fluoxetine and norfluoxetine levels support the safety of fluoxetine in overdose Stephanie Pope 0 Solomon G. Zaraa 0 0 Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospitals Cleveland Medical Center , 10524 Euclid Ave, WO Walker Building, First Floor, Cleveland, OH , USA Background: Previous literature has found fluoxetine to be relatively safe in overdose. This study hopes to examine this idea along with support from published pharmacokinetic information including serum fluoxetine and norfluoxetine levels based on information from a clinical case series. Methods: Four cases are presented along with vital abnormalities, electrocardiogram abnormalities, and physical exam abnormalities along with amount of overdose and resulting serum fluoxetine and norfluoxetine levels. Case Presentation: In these four cases, serum fluoxetine and norfluoxetine days after overdose were found to be in a range believed to be within the treatment range. No abnormalities were found on electrocardiogram but some patients (3) were found to have slight elevations in heart rate. Conclusion: Fluoxetine is relatively safe in overdose. This study supports previous literature. Future directives for research can be directed towards when serotonergic, including fluoxetine, medications can be introduced or restarted in patients who have overdosed. Research could also focus on if the introduction of another medication, such as carbamazepine, to induce metabolism of a medication, such as fluoxetine, after an overdose. - Background Previous research has provided ample evidence to conclude fluoxetine without tricyclic antidepressants as relatively safe in overdose. Early literature found sinus tachycardia, convulsions, depressed ST segments on electrocardiogram (ECG), elevated diastolic blood pressure, drowsiness, and agitation in a series of case reports and chart reviews of fluoxetine in overdose [1–5]. A larger chart review of 234 cases was completed including 20 pediatrics patients and 67 patients who ingested fluoxetine alone. In this chart review, the 20 pediatric patients ranged in age between 10  months and 4  years old. The mean dose ingested was 23.4  mg or 1.76  mg/kg. Of the 20 pediatric patients, 18 remained asymptomatic, while hyperactivity and diarrhea were reported in a 2-year-old and sleepiness was reported in a 23-month old. Of the 67 adults in this study, the mean dose ingested was 544 mg, while 30 were asymptomatic, 15 were found to have tachycardia, 14 reported drowsiness, five with tremor, four with vomiting and four with nausea, one with euphoria, one with headache, one with sore throat, one with trigeminy, one with junctional rhythm, and one with abdominal pain [6]. Meanwhile, serum concentrations of fluoxetine and its active demethylated metabolite, norfluoxetine, have been studied. One study found four patients were treated with 80  mg/day for 52  ±  8  weeks and had their serum measured for fluoxetine and norfluoxetine while taking the medication and then 4 and 8  weeks after discontinuation. Mean fluoxetine and norfluoxetine levels during treatment were 620  ±  49  ng/ml and 496  ±  49  ng/ ml, respectively. After 4  weeks of discontinuation, mean fluoxetine and norfluoxetine levels during treatment were 55  ±  19  ng/ml and 184  ±  40  ng/ml, respectively. After 8 weeks of discontinuation, fluoxetine and norfluoxetine levels during treatment were 0 ng/ml and 47 ± 20 ng/ml, © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. respectively. Age and sex of the patient did not impact metabolism of this study [7]. Two other studies found sex did impact serum concentrations and metabolisms. In a study of 10–17 year olds [8] and adults [9], it was found that males had lower fluoxetine and norfluoxetine serum levels similar to comparing Case 1 and Case 2 although admitting vastly less sophisticated. Unfortunately, Patients have continued to overdose with fluoxetine. The purpose of this study is to examine serum fluoxetine and norfluoxetine levels as a product of time from fluoxetine overdose in relationship to their clinical presentations. The goal of this study is to address the gap of knowledge and complications from fluoxetine overdose in clinical cases. The hypothesis of this study is that fluoxetine is relatively safe in overdose. Methods Participants were identified by the authors as minors admitted (...truncated)


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Stephanie Pope, Solomon Zaraa. Serum fluoxetine and norfluoxetine levels support the safety of fluoxetine in overdose, Annals of General Psychiatry, 2016, pp. 30, 15, DOI: 10.1186/s12991-016-0117-z