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.
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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,
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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)