Isolated atomoxetine overdose resulting in seizure

Kashani, John; Ruha, Anne‐Michelle

doi:10.1016/j.jemermed.2006.05.048

Cited by 31 publications

(18 citation statements)

References 4 publications

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“…The concomitant medications for these first two patients included drugs that are inhibitors of CYP2D6 metabolism and were confounded by co‐ingestants that could have influenced QT c . A 17‐year‐old, treated with no other medications, took an overdose of atomoxetine alone (2840 mg) and was reported to have a QT c of 476 ms with sinus tachycardia of 103 beats per min (correction method not reported but value consistent with Bazett method) .…”

Section: Introductionmentioning

confidence: 99%

Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

Loghin

Haber²,

Beasley

et al. 2013

Brit J Clinical Pharma

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AIMThe effects of atomoxetine (20 and 60 mg twice daily), 400 mg moxifloxacin and placebo on QTc in 131 healthy CYP2D6 poor metabolizer males were compared. METHODSAtomoxetine doses were selected to result in plasma concentrations that approximated expected plasma concentrations at both the maximum recommended dose and at a supratherapeutic dose in CYP2D6 extensive metabolizers. Ten second electrocardiograms were obtained for time-matched baseline on days -2 and -1, three time points after dosing on day 1 for moxifloxacin and five time points on day 7 for atomoxetine and placebo. Maximum mean placebo-subtracted change from baseline model-corrected QT (QTcM) on day 7 was the primary endpoint. RESULTSQTcM differences for atomoxetine 20 and 60 mg twice daily were 0.5 ms (upper bound of the one-sided 95% confidence interval 2.2 ms) and 4.2 ms (upper bound of the one-sided 95% confidence interval 6.0 ms), respectively. As plasma concentration of atomoxetine increased, a statistically significant increase in QTc was observed. The moxifloxacin difference from placebo met the a priori definition of non-inferiority. Maximum mean placebo-subtracted change from baseline QTcM for moxifloxacin was 4.8 ms and this difference was statistically significant. Moxifloxacin plasma concentrations were below the concentrations expected from the literature. However, the slope of the plasma concentration-QTc change observed was consistent with the literature.

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Section: Introductionmentioning

confidence: 99%

Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

Loghin

Haber²,

Beasley

et al. 2013

Brit J Clinical Pharma

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“…However, case reports documenting fatal cardiac events and seizures associated with atomoxetine use and overdose have been reported. [32][33][34] Atomoxetine, as a selective norepinephrine reuptake inhibitor, increases overall availability of norepinephrine that has been shown to result in elevations in heart rate and blood pressure. 35,36 This drug has also been reported to inhibit hERG current in vitro, 37 the potassium (I Kr ) current implicated in LQT2.…”

Section: Discussionmentioning

confidence: 99%

Long‐QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder

Zhang

Kutyifa

Moss

et al. 2015

Cardiovasc electrophysiol

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Introduction Stimulants are the mainstay therapy for attention deficit/hyperactivity disorder (ADHD) and are associated with adrenergic side effects. There is limited data on the clinical course of patients treated for ADHD who have long-QT syndrome (LQTS), for which β-blockade is the goal of therapy. Methods LQTS patients from the Rochester-based LQTS Registry (open-enrollment between 1979–2003; follow-up from 1979 to present) treated with stimulant or non-stimulant ADHD medications (n=48) were compared to a 2:1 age-, gender-, and QTc-duration matched LQTS control group not exposed to ADHD medications (n=96). Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate risk of cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) in LQTS patients treated with ADHD medications. Results During a mean follow-up of 7.9 ±5.4 years after initiation of ADHD medication at a mean age 10.7 ±7.3 years, there was a 62% cumulative probability of cardiac events in the ADHD treatment group compared to 28% in the matched LQTS control group (p<0.001). Time-dependent use of ADHD medication was associated with an increased risk for cardiac events (HR=3.07; p=0.03) in the multivariate Cox model adjusted for time-dependent β-blocker use and prior cardiac events. Subgroup gender analyses showed that time-dependent ADHD medication was associated with an increased risk in male LQTS patients (HR=6.80, p=0.04). Conclusions LQTS patients treated with ADHD medications have increased risk for cardiac events, particularly syncope, and this risk is augmented in males. The findings highlight the importance of heightened surveillance for LQTS patients on ADHD medications.

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“…There are rare reports of seizures with ATX and the percentage has been 0.1-0.2% (Wernicke et al ., 2007[128]). No deaths have been reported when poison centre reports were analysed for ATX overdoses, and doses up to 2840 mg have been reported to cause seizures and GI problems (Kashani and Ruha, 2007[56]; Spiller et al ., 2005[113]). In a double-blind study in 6- to 16-year-old outpatients with ADHD from three different countries, Wang et al ., 2007[126], reported a higher incidence of adverse effects with ATX compared to MPH.…”

Section: Non Stimulantsmentioning

confidence: 99%

Drug therapy of attention deficit hyperactivity disorder: Current trends

Sousa¹,

Kalra²

2012

Mens Sana Monogr

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Attention deficit hyperactivity disorder is a developmental disorder with an age onset prior to 7 years. Children with ADHD have significantly lower ability to focus and sustain attention and also score higher on impulsivity and hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of ADHD treatment for decades with evidence supporting their use. However, recent years have seen emergence of newer drugs and drug delivery systems, like osmotic release oral systems and transdermal patches, to mention a few. The use of nonstimulant drugs like atomoxetine and various other drugs, such as α-agonists, and a few antidepressants, being used in an off-label manner, have added to the pharmacotherapy of ADHD. This review discusses current trends in drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the future.

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Isolated atomoxetine overdose resulting in seizure

Cited by 31 publications

References 4 publications

Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

Long‐QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder

Drug therapy of attention deficit hyperactivity disorder: Current trends

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