Atomoxetine - Wikipedia, the free encyclopedia

Atomoxetine (brand name: Strattera) is a drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD).[4] It is a selective norepinephrine reuptake inhibitor (NRI),[4] not to be confused with serotonin norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs), both of which are currently the most prescribed form of antidepressants.[5]

Medical use[edit]

Attention deficit-hyperactivity disorder[edit]

Classified as a norepinephrine (noradrenaline) reuptake inhibitor, atomoxetine is approved for use in children, adolescents, and adults.[4] However, its efficacy has not been studied in children under six years old.[2] Its primary advantage over the standard stimulant treatments for ADHD is that it has no abuse potential.[2]

The initial therapeutic effects of atomoxetine usually take 2–4 weeks to be become apparent.[1] A further 2–4 weeks may be required for the full therapeutic effects to be seen.[5] Its efficacy may be less than that of stimulant medications.[6]

Unlike α2 adrenoceptor agonists such as guanfacine and clonidine atomoxetine's use can be abruptly stopped without significant withdrawal effects being seen.[2]

Investigational uses[edit]

There has been some suggestion that atomoxetine might be a helpful adjunct in people with major depression, especially in cases where ADHD occurs comorbidly to major depression.[7][8][9] Several randomised double-blind placebo-controlled trials found that atomoxetine was an efficacious treatment for various disorders like paediatric bedwetting,[10]binge eating disorder,[11] and is an efficacious weight loss medication.[12]

Adverse effects[edit]

Incidence of adverse effects:[2][3][13][14]

Very common (>10% incidence) adverse effects include:

Common (1-10% incidence) adverse effects include:

Uncommon (0.1-1% incidence) adverse effects include:

Rare (0.01-0.1% incidence) adverse effects include:

The FDA of the US has issued a black box warning for suicidal behaviour/ideation.[3] Similar warnings have been issued in Australia.[2][16] Unlike stimulant medications atomoxetine does not have abuse liability or the potential to cause withdrawal effects on abrupt discontinuation.[2]


Contraindications include:[2]

-moderate to severe hypertension-atrial fibrillation-atrial flutter-ventricular tachycardia-ventricular fibrillation-or ventricular flutter-advanced arteriosclerosis


Atomoxetine is a substrate for CYP2D6 and hence concurrent treatment with CYP2D6 inhibitors or inducers is not recommended as this can lead to significant elevations or reductions of plasma atomoxetine levels, respectively.[2] Other possible drug interactions include with:[2]


Atomoxetine is relatively non-toxic in overdose as single-drug overdoses involving over 1500 mg of atomoxetine have not resulted in death.[2] The most common symptoms of overdose include:[2]

and less commonly:[2]

Recommended treatment of overdoses include activated charcoal treatment to prevent further absorption of the drug.[2]

Detection in biological fluids[edit]

Atomoxetine may be quantitated in plasma, serum or whole blood in order to distinguish extensive versus poor metabolizers in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.[17]

Chemistry and composition[edit]

Atomoxetine is designated chemically as (−)-N-methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride, and has a molecular mass of 291.82.[4] It has a solubility of 27.8 mg/mL in water.[4] Atomoxetine is a white solid that exists as a granular powder inside the capsule, along with pre-gelatinized starch and dimethicone.[4] The capsule shells contain gelatin, sodium lauryl sulfate, FD&C Blue No. 2, synthetic yellow iron oxide, titanium dioxide, red iron oxide, edible black ink, and trace amounts of other inactive ingredients.[4]


Atomoxetine inhibits NET, SERT and DAT with respective Ki values of 5, 77 and 1451 nM.[18] In microdialysis studies it increased NE and DA levels by 3 fold in the prefrontal cortices but did not alter DA levels in the striatum or nucleus accumbens.[19] Atomoxetine also acts as an NMDA-receptor antagonist at clinically relevant doses.[20] The role of NMDA-receptor antagonism in atomoxetine's therapeutic profile remains to be further elucidated, but recent literature has further implicated glutaminergic dysfunction as central in ADHD pathophysiology and etiology.[21][22]

4-hydroxyatomoxetine, the principle metabolite of atomoxetine, exhibits affinity for μ-opioid receptors and κ-opioid receptors. Creighton et al. reported no activation of μ-opioid receptors and a partial agonist effect at κ-opioid receptors.[23] The clinical significance of these effects are not known.

Atomoxetine has been found to inhibit both brain and cardiac GIRKs, a characteristic it shares with the norepinephrine reuptake inhibitorreboxetine.[24]

Binding profile[18][19][23][25]


First step appears to be a Mannich reaction between acetophenone, paraformaldehyde and dimethylamine, although not formally written in the scheme.

Foster, B. J.; Lavagnino, E. R.; European Patent, 1982, EP 0052492 .


This compound is manufactured, marketed and sold in the United States under the brand name Strattera by Eli Lilly and Company as a hydrochloride salt (atomoxetine HCl), the original patent filing company, and current U.S. patent owner. Strattera was approved by the FDA in 2006 for the treatment of ADHD. There is currently no generic manufactured directly in the United States since it is under patent until 2017.[26] On 12 August 2010, Lilly lost a lawsuit that challenged Lilly's patent on Strattera, increasing the likelihood of an earlier entry of a generic into the US market.[27] On 1 September 2010, Sun Pharmaceuticals announced it would begin manufacturing a generic in the United States.[28] In a 29 July 2011 conference call, however, Sun Pharmaceutical's Chairman stated "Lilly won that litigation on appeal so I think [generic Strattera]’s deferred."[29]

Production and brand-names[edit]

In India, Atomoxetine is found under different names like Tomoxetin, Attentrol, Axepta, Atokem and Attentin.


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  3. ^ abcdefg"ATOMOXETINE HYDROCHLORIDE capsule [Mylan Pharmaceuticals Inc.]". DailyMed. Mylan Pharmaceuticals Inc. October 2011. Retrieved 10 November 2013. 
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  5. ^ abTaylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry (in English). West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8edit
  6. ^Kooij, JJS (2013). Adult ADHD Diagnostic Assessment and Treatment (PDF). Springer London. doi:10.1007/978-1-4471-4138-9. ISBN 9781447141372
  7. ^Spencer TJ, Faraone SV, Michelson D, Adler, LA; Reimherr, FW; Glatt, SJ; Biederman, J (March 2006). "Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity". The Journal of Clinical Psychiatry67 (3): 415–20. doi:10.4088/JCP.v67n0312. PMID 16649828
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  10. ^Sumner, CR; Schuh, KJ; Sutton, VK; Lipetz, R; Kelsey, DK (December 2006). "Placebo-controlled study of the effects of atomoxetine on bladder control in children with nocturnal enuresis". Journal of Child and Adolescent Psychopharmacology16 (6): 699–711. doi:10.1089/cap.2006.16.699. PMID 17201614
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  12. ^Gadde, KM; Yonish, GM; Wagner, HR; Foust, MS; Allison, DB (July 2006). "Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial". International Journal of Obesity30 (7): 1138–42. doi:10.1038/sj.ijo.0803223. PMID 16418753
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  17. ^Baselt, Randall C. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 118–20. ISBN 0-931890-08-X
  18. ^ abRoth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 10 November 2013. 
  19. ^ abBymaster, FP; Katner, JS; Nelson, DL; Hemrick-Luecke, SK; Threlkeld, PG; Heiligenstein, JH; Morin, SM; Gehlert, DR; Perry, KW (November 2002). "Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat: A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder" (PDF). Neuropsychopharmacology27 (5): 699–711. doi:10.1016/S0893-133X(02)00346-9. PMID 12431845
  20. ^Ludolph, AG; Udvardi, PT; Schaz, U; Henes, C; Adolph, O; Weigt, HU; Fegert, JM; Boeckers, TM; Föhr, KJ (May 2010). "Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations" (PDF). British Journal of Pharmacology160 (2): 283–291. doi:10.1111/j.1476-5381.2010.00707.x. PMC 2874851. PMID 20423340
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  22. ^Children's Hospital of Philadelphia: New gene study of ADHD points to defects in brain signaling pathways
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  27. ^"Drugmaker Eli Lilly loses patent case over ADHD drug, lowers revenue outlook". Chicago Tribune. 
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  29. ^"Sun Pharma Q1 2011-12 Earnings Call Transcript 10.00 am, July 29, 2011"

External links[edit]