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Atomoxetine
Atomoxetine is a phenol ether and selective norepinephrine reuptake inhibitor medication used to treat attention deficit hyperactivity disorder in children and adults. It may also treat cognitive disengagement syndrome and can be used alone or with stimulant medication. Common adverse effects include abdominal pain, reduced appetite, nausea, fatigue, and dizziness. More serious reported outcomes include liver and cardiovascular problems, psychosis, suicidal behavior, aggression, stroke, and angioedema.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
Atomoxetine inhibits the presynaptic norepinephrine transporter, reducing norepinephrine reuptake throughout the brain and increasing norepinephrine and dopamine concentrations in the prefrontal cortex, where dopamine transporter expression is minimal. In rats and mice, these catecholamine changes were region-specific, and rat studies found no corresponding dopamine increase in the striatum or nucleus accumbens. Rhesus monkey PET imaging measured greater than 90% NET occupancy and greater than 85% SERT occupancy, but SERT inhibition at clinical doses in humans remains uncertain because rodent microdialysis and a human platelet serotonin uptake study did not show functional evidence of serotonin reuptake inhibition. At therapeutic concentrations, atomoxetine produced use-dependent open-channel block of NMDA receptors in rat cortical neurons and reversibly inhibited GIRK currents in Xenopus oocytes, although the contribution of GIRK inhibition to its therapeutic effects is unknown. Atomoxetine also directly inhibited hERG potassium currents with an IC50 of 6.3 μM.
Pharmacokinetics
Atomoxetine is rapidly and completely absorbed after oral administration, but CYP2D6-dependent first-pass hepatic metabolism produces an absolute bioavailability of 63% in extensive metabolizers and 94% in poor metabolizers. CYP2D6 is the primary metabolic pathway, with a major oxidative metabolite undergoing rapid glucuronidation; when CYP2D6 activity is absent, this metabolite forms more slowly through other cytochrome P450 enzymes, while CYP2C19 and other enzymes produce a less active minor metabolite. CYP2D6 poor metabolizers have approximately 10-fold higher steady-state exposure, 5-fold higher peak plasma concentrations, and slower elimination, with a plasma half-life of 21.6 hours, while the generally reported half-life is 3 to 5.6 hours. Atomoxetine is 98.7% plasma protein bound and is extensively transformed before excretion, with more than 80% of the dose eliminated in urine, less than 17% in feces, and less than 3% excreted unchanged.
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Harm Potential
Toxicity
Severe atomoxetine overdose can cause cardiac complications requiring intensive medical care to prevent death.
Sudden death, stroke, and myocardial infarction have been reported during usual-dose atomoxetine treatment, while QT prolongation has occurred at therapeutic doses and in overdose.
Atomoxetine can rarely cause clinically significant liver injury, including liver failure requiring transplantation.
Short-term studies found an increased risk of suicidal ideation among children and adolescents treated with atomoxetine for ADHD.
Psychosis Risk
Atomoxetine at usual doses can cause treatment-emergent hallucinations, delusional thinking, or mania in children and adolescents without a previous history of psychotic illness or mania. Disorientation and hallucinations have also been reported less commonly in overdose.
Seizure Risk
Seizures have been reported in some atomoxetine overdoses.
History & Culture
Atomoxetine was initially developed as an antidepressant, but it was found insufficiently effective for treating depression. Its effectiveness for ADHD led to approval by the U.S. Food and Drug Administration in 2002.…
Legality
By Country
United StatesPrescription only
CanadaPrescription onlyReferences
Citations
Article Status
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