Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS). She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays. 1. Introduction Atomoxetine is classified as a selective norepinephrine reuptake inhibitor and is commonly prescribed as a nonstimulant treatment for the management of ADHD in children and adults. The drug acts at presynaptic norepinephrine transporters in neurons blocking removal of norepinephrine from the synaptic cleft through a mechanism that is not fully understood [1]. The primary oxidative metabolite of atomoxetine is 4-hydroxyatomoxetine (active metabolite but present in a much lower concentration compared to the parent drug) which is subsequently conjugated to 4-hydroxyatomoxetine- -glucoronide via the cytochrome P450 CYP2D6 pathway [1–3]. To a lesser extent, atomoxetine is demethylated to -desmethylatomoxetine, which is substantially less active compared to the parent drug. Structurally, atomoxetine [ -methyl-3-(2-methylphenoxy)-3-phenylpropan-1-amine] bears some similarities to amphetamine [1-phenylpropan-2-amine] (Figure 1) [1, 3]. Recent research also suggests that atomoxetine blocks -methyl- -aspartate (NMDA) receptors altering glutaminergic transmission, and this mechanism may contribute to its efficacy as a treatment for ADHD [4]. Figure 1: Chemical structure of atomoxetine and its main metabolites -desmethylatomoxetine and 4-hydroxyatomoxetine compared with that of amphetamine [ 3]. To our knowledge, neither atomoxetine nor its metabolites, have previously been reported in