Off-label use of atomoxetine in adults: Is it safe?

Mental Illness

Volumn 4, Issue 2, 2012, Pages 96-101

  Dadashova, Rana ^a   Silverstone, Peter H ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Adults; Atomoxetine; Clinical trial; Double blind; Placebo controlled; Safety

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; ATOMOXETINE; DEXAMPHETAMINE; METHYLPHENIDATE; PHENTERMINE; PLACEBO;

ADDICTION; ATTENTION DEFICIT DISORDER; CARDIOVASCULAR DISEASE; CLOSED ANGLE GLAUCOMA; COGNITIVE DEFECT; CONSTIPATION; DECREASED APPETITE; DEPRESSION; DIASTOLIC BLOOD PRESSURE; DIZZINESS; DRUG APPROVAL; DRUG FATALITY; DRUG MECHANISM; DRUG MEGADOSE; DRUG OVERDOSE; DRUG SAFETY; DRUG TOLERANCE; DRUG USE; EATING DISORDER; ERECTILE DYSFUNCTION; ERUCTATION; FATIGUE; GILLES DE LA TOURETTE SYNDROME; HEART ARRHYTHMIA; HEART RATE; HOT FLUSH; HUMAN; HYPERTENSION; HYPONATREMIA; INSOMNIA; LACTATION; LIBIDO DISORDER; MANIA; MOOD DISORDER; NAUSEA; NERVOUSNESS; NONHUMAN; OFF LABEL DRUG USE; PATIENT MONITORING; PREGNANT WOMAN; RELAPSE; REVIEW; SEIZURE; SIDE EFFECT; SUDDEN DEATH; SWEATING; SYSTOLIC BLOOD PRESSURE; TIC; TOBACCO DEPENDENCE; URINARY HESITANCY; URINARY TRACT OBSTRUCTION; URINE RETENTION; UROGENITAL TRACT DISEASE; XEROSTOMIA;

EID: 84866849832     PISSN: 20367457     EISSN: 20367465     Source Type: Journal    
DOI: 10.4081/mi.2012.e19     Document Type: Review

References (97)

1. Wong DT, Threlkeld PG, Best KL, Bymaster FP. A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther 1982;222:61-65.
2. Garnock-Jones KP, Keating GM. Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paed Drugs 2009;11:203-226.
3. Gehlert DR, Gackenheimer SL, Robertson DW. Localization of rat brain binding sites for [3H]tomoxetine, an enantiomerically pure ligand for norepinephrine reuptake sites. Neurosci Lett 1993;157:203-206.
4. Zerbe RL, Rowe H, Enas GG, et al. Clinical pharmacology of tomoxetine, a potential antidepressant. J Pharmacol Exp Ther 1985;232:139-143.
5. Sauer JM, Ring BJ, Witcher JW. Clinical pharmacokinetics of atomoxetine. Clin Pharmacokinet 2005;44:571-590.
6. Swanson CJ, Perry KW, Koch-Krueger S, et al. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology 2006;50:755-760.
7. Koda K, Ago Y, Cong Y, et al. Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice. J Neurochem 2010;114:259-270.
8. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/ hyperactivity disorder. Neuropsycho pharmacol 2002;27:699-711.
9. de Jong CG, Van De Voorde S, Roeyers H, et al. Differential effects of atomoxetine on executive functioning and lexical decision in attention-deficit/hyperactivity disorder and reading disorder. J Child Adol Psychopharmacol 2009;19:699-707.
10. Faraone SV, Biederman J, Spencer T, et al. Atomoxetine and stroop task performance in adult attention-deficit/hyperactivity disorder. J Child Adol Psychopharmacol 2005;15:664-670.
11. Michelson D, Adler L, Spencer T, et al. Atomoxetine in adults with ADHD: Two randomized placebo-controlled studies. Biol Psychiat 2003;53:112-20.
12. Adler L, Dietrich A, Reimherr FW, et al. Safety and tolerability of once versus twice daily atomoxetine in adults with ADHD. Ann Clin Psychiat 2006;18:107-113.
13. Adler LA, Spencer TJ, Levine LR, et al. Functional outcomes in the treatment of adults with ADHD. J Attention Disord 2008;11:720-727.
14. Adler LA, Spencer T, Brown TE, et al. Oncedaily atomoxetine for adult attentiondeficit/ hyperactivity disorder: a 6-month double-blind trial. J Clin Psycho pharmacol 2009;29: 44-50.
15. Santosh PJ Sattar S Canagaratnam M. Efficacy and tolerability of pharmacotherapies for attention-deficit hyperactivity disorder in adults. CNS Drugs 2011;25:737-763.
16. Simpson D Plosker GL. Spotlight on atom-oxetine in adults with attention-deficit hyperactivity disorder. CNS Drugs 2004;18:397-401.
17. Dell'osso B, Palazzo MC, Oldani L, Altamura AC. The noradrenergic action in antidepressant treatments: pharmacological and clinical aspects. CNS Neurosci Ther 2011;17:723-732.
18. Blier P. Psychopharmacology for the clinician. Treating depression with selective norepinephrine reuptake inhibitors. J Psychiatry Neurosci 2006;31:288.
19. Chouinard G, Annable L, Bradwejn J. An early phase II clinical trial of tomoxetine (LY139603) in the treatment of newly admitted depressed patients. Psycho - pharmacology 1984;83:126-128.
20. Carpenter LL, Milosavljevic N, Schecter JM, et al. Augmentation with open-label atomoxetine for partial or nonresponse to antidepressants. J Clin Psychiatry 2005;66:1234-1238.
21. Kratochvil CJ, Newcorn JH, Arnold LE, et al. Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. J Am Acad Child Adolesc Psychiatry 2005;44: 915-924.
22. Michelson D, Adler LA, Amsterdam JD, et al. Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized double-blind placebo-controlled study. J Clin Psychiat 2007;68:582-587.
23. Preti A. Tomoxetine (Eli Lilly & Co). Curr Opin Investig Drugs 2002;3:272-277.
24. Spencer TJ, Faraone SV, Michelson D, et al. Atomoxetine and adult attentiondeficit/hyperactivity disorder: the effects of comorbidity. J Clin Psychiat 2006;67: 415-420.
25. Bangs ME, Emslie GJ, Spencer TJ, et al. Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression. J Child Adolesc Psychopharmacol 2007;17:407-420.
26. Michelson D, Adler LA, Amsterdam JD, et al. Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized double-blind placebo-controlled study. J Clin Psychiat 2007;68:582-587.
27. Weintraub D, Mavandadi S, Mamikonyan E, et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology 2010;75: 448-455.
28. McElroy SL, Guerdjikova A, Kotwal R, et al. Atomoxetine in the treatment of binge-eating disorder: A randomized placebo-controlled trial. J Clin Psychiat 2007;68: 390-398.
29. Gadde KM, Yonish GM, Wagner HR, et al. Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial. Int J Obesity 2006;30:1138-1142.
30. Morein-Zamir S, Robbins T, Turner D, Sahakian B. UK government's foresight project mental capital and wellbeing: making the most of ourselves in the 21st century. State-of-Science Review: SR-E9 Pharmacological Cognitive Enhancement, 2005.
31. Beglinger LJ, Adams WH, Paulson H, et al. Randomized controlled trial of atomoxetine for cognitive dysfunction in early huntington disease. J Clin Psychopha rmacol 2009;29:484-487.
32. Marsh L, Biglan K, Gerstenhaber M, Williams JR. Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: a pilot open-label study. Mov Disord 2009;24:277-282.
33. Weinshenker D, Schroeder JP. There and back again: a tale of norepinephrine and drug addiction. Neuropsychopharmacol 2007;32:1433-1451.
34. Jasinski DR, Faries DE, Moore RJ, et al. Abuse liability assessment of atomoxetine in a drug-abusing population. Drug Alcohol Depend 2008;95:140-146.
35. Heil SH, Holmes HW, Bickel WK, et al. Comparison of the subjective physiological and psychomotor effects of atomoxetine and methylphenidate in light drug users. Drug Alcohol Depend 2002;67:149-156.
36. Lile JA, Stoops WW, Durell TM, et al. Discriminative-stimulus self-reported performance and cardiovascular effects of atomoxetine in methylphenidate-trained humans. Exp Clin Psychopharmacol 2006; 14:136-147.
37. Sofuoglu M Sewell RA. Noradrenaline and stimulant addiction. Addict Biol 2009; 14:119-129.
38. Levin FR, Mariani JJ, Secora A, et al. Atomoxetine treatment for cocaine abuse and adult attention-deficit hyperactivity disorder (ADHD): a preliminary open trial. J Dual Diagnosis 2009;5:41-56.
39. Thurstone C, Riggs PD, Salomonsen-Sautel S, Mikulich-Gilbertson SK. Rando mized controlled trial of atomoxetine for attention-deficit/hyperactivity disorder in adolescents with substance use disorder. J Am Acad Child Adolesc Psychiatry 2010;49:573-582.
40. Stoops WW, Blackburn JW, Hudson DA, et al. Safety tolerability and subject-rated effects of acute intranasal cocaine administration during atomoxetine maintenance. Drug Alcohol Depend 2008;92:282-285.
41. Tirado CF, Goldman M, Lynch K, et al. Atomoxetine for treatment of marijuana dependence: a report on the efficacy and high incidence of gastrointestinal adverse events in a pilot study. Drug Alcohol Depend 2008;94:254-257.
42. Ray R, Rukstalis M, Jepson C, et al. Effects of atomoxetine on subjective and neurocognitive symptoms of nicotine abstinence. J Psychopharmacol 2009;23:68-176.
43. Gehricke JG, Hong N, Wigal TL, et al. ADHD medication reduces cotinine levels and withdrawal in smokers with ADHD. Pharmacol Biochem Behav 2011;98:485-491.
44. Sacco KA, Creeden C, Reutenauer EL, et al. Effects of atomoxetine on cognitive function and cigarette smoking in schizophrenia. Schizophren Res 2009;107:332-333.
45. Silverstone PH Dadashova R. Atomoxetine treatment for nicotine withdrawal: a pilot double-blind, placebo-controlled, fixed-dose study in adult smokers. Annals General Psychiatry 2012;11:6.
46. Product monograph. Strattera. Eli Lilly Canada.Available from: http://www.lilly.ca/en?t=/contentManager/selectCatalog&i=1306943185696&l=0&e=UTF-8& ParentID=1246635267998. Accessed on: September 26th , 2011.
47. Rajesh AS, Bates G, Wright JGC. Atomoxetine induced electrocardiogram changes. Arch Dis Child 2006;91:1023-1024.
48. Dworkin N. Increased blood pressure and atomoxetine. J Am Acad Child Adolesc Psychiatry 2005;44:510.
49. Shibao C, Raj SR, Gamboa A, et al. Norepinephrine transporter blockade with atomoxetine induces hypertension in patients with impaired autonomic function. Hypertension 2007;50:47-53.
50. McCarthy S, Cranswick N, Potts L, et al. Mortality associated with attention-deficit hyperactivity disorder (ADHD) drug treatment: a retrospective cohort study of children adolescents and young adults using the general practice research database. Drug Saf 2009;32:1089-1096.
51. Schelleman H, Bilker WB, Strom BL, et al. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics 2011;127:1102-1110.
52. Garside D, Ropero-Miller JD, Riemer EC. Postmortem tissue distribution of atomoxetine following fatal and nonfatal doses three case reports. J Forensic Sci 2006; 51:179-182.
53. Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA 2011;306:2673-2683.
54. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 2011;365:1896-1904.
55. Kratochvil CJ, Milton DR, Vaughan BS, Greenhill LL. Acute atomoxetine treatment of younger and older children with ADHD: a meta-analysis of tolerability and efficacy. Child Adolesc Psychiatry Ment Health 2008;2:25.
56. Wernicke JF, Faries D, Girod D, et al. Cardiovascular effects of atomoxetine in children adolescents and adults. Drug Saf 2003;26:729-740.
57. Arnold LE, Aman MG, Cook AM, et al. Atomoxetine for hyperactivity in autismspectrum disorders: placebo-controlled crossover pilot trial. J Am Acad Child Adolesc Psychiatry 2006;45:1196-205.
58. Johnson M, Cederlund M, Rastam M, et al. Open-label trial of atomoxetine hydrochloride in adults with ADHD. J Attention Dis 2010;13;539-45.
59. Quintana H, Cherlin EA, Duesenberg DA, et al. Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder - a preliminary tolerability and efficacy study. Clin Ther 2007:29:1168-77.
60. European Medicines Agency, Pharmaco - vigilance working party, 24th November 2011 plenary meeting. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/11/WC500117988.pdf
61. Grossman L. Association of STRATTERA (atomoxetine) with increased blood pressure and increased heart rate. Health Canada letter to Health Care Professionals 21st October 2011. Available from: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2011/strattera_2_hpc-cps-eng.pdf
62. Australian Government, Department of Health and Aging, Safety Advisory, 2nd November 2011. Available from: http://www.tga.gov.au/safety/alerts-medicine-atomoxetine-111102.htm
63. Health Sciences Authority, Singapore Government, 8th November 2011. Available from: http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/safety_information/DHCPL/2011.html
64. United States Food and Drug Administration (FDA). FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention- Deficit/Hyperactivity Disorder (ADHD) in children and young adults, 1st November 2011. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm277770.htm
65. Singh T. Atomoxetine-induced hyponatremia. Aust N Z J Psychiatry 2007;41:458.
66. Raj YP. Atomoxetine-associated hemospermia: a case report. J Clin Psychiat 2008;69:1189.
67. Steinberg S, Chouinard G. A case of mania associated with tomoxetine. Am J Psychiatry1985;142:1517-1518.
68. Bangs ME, Jin L, Zhang S, et al. Hepatic events associated with atomoxetine treatment for attention-deficit hyperactivity disorder. Drug Safety 2008;31:345-354.
69. Lovecchio F Kashani J. Isolated atomoxetine (Strattera) ingestions commonly result in toxicity. J Emerg Med 2006;31:267-268.
70. Sawant S Daviss SR. Seizures and prolonged QTc with atomoxetine overdose. Am J Psychiatry 2004;161:757.
71. Kashani J, Ruha AM. Isolated atomoxetine overdose resulting in seizure. J Emerg Med 2007;32:175-178.
72. Alhatem FJ, Decker DH. Atomoxetineinduced mydriasis. J Am Acad Child Adolesc Psychiatry 2008;18:539-541.
73. Yu Y, Koss MC. Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats. Eur J Pharmacol 2003;471:135-140.
74. Robertson MM. Attention deficit hyperactivity disorder tics and Tourette's syndrome: the relationship and treatment implications. A commentary. Eur Child Adolesc Psychiatry 2006;15:1-11.
75. Block SL, Kelsey D, Coury D, et al. Oncedaily atomoxetine for treating pediatric attention-deficit/hyperactivity disorder: comparison of morning and evening dosing. Clin Pediatr 2009;48:723-733.
76. Spencer TJ, Sallee FR, Gilbert DL, et al. Atomoxetine treatment of ADHD in children with comorbid Tourette syndrome. J Atten Disord 2008;11:470-481.
77. Wolraich ML, McGuinn L, Doffing M. Treatment of attention deficit hyperactivity disorder in children and adolescents: safety considerations. Drug Safety 2007; 30:17-26.
78. Lee TS, Lee TD, Lombroso PJ, King RA. Atomoxetine and tics in ADHD. J Am Acad Child Adolesc Psychiat 2004;43:1068-1069.
79. Sears J, Patel NC. Development of tics in a thirteen-year-old male following atomoxetine use. CNS Spectrums 2008;13:301-303.
80. Ledbetter M. Atomoxetine use associated with onset of a motor tic. J Child Adolesc Psychopharm 2005;15:331-333.
81. Parraga HC, Parraga MI, Harris DK. Tic exacerbation and precipitation during atomoxetine treatment in two children with attention-deficit hyperactivity disorder. Int J Psychiat Med 2007;37:415-424.
82. Jaworowski S, Benarroch F, Gross-Tsur. Concomitant use of atomoxetine and OROS-methylphenidate in a 10-year-old child suffering from attentiondeficit/hyperactivity disorder with comorbid bipolar disorder and Tourette syndrome. J Child Adolesc Psychopharm 2006;16:365-370.
83. Parraga HC, Parraga KL, Harris DK, Campbell TS. Abdominal tics during atomoxetine treatment in a child with ADHD: evaluation and differential diagnosis. CNS Spectrums 2008;13:E1.
84. Torres AR, Whitney J, Gonzalez-Heydrich J. Attention-deficit/hyperactivity disorder in pediatric patients with epilepsy: review of pharmacological treatment. Epilep Behav 2008;12:217-233.
85. Sawant S, Daviss SR. Seizures and prolonged QTc with atomoxetine overdose. Am J Psychiatry 2004;161:757.
86. Spiller HA, Lintner CP, Winter ML. Atomoxetine ingestions in children: a report from poison centers. Ann Pharma - cother 2005;39:1045-1048.
87. Kashani J, Ruha AM. Isolated atomoxetine overdose resulting in seizure. J Emerg Med 2007;32:175-178.
88. Graham J, Coghill D. Adverse effects of pharmacotherapies for attention-deficit hyperactivity disorder: epidemiology prevention and management. CNS Drugs 2008;22:213-237.
89. Wernicke JF, Holdridge KC, Jin L, et al. Seizure risk in patients with attentiondeficit-hyperactivity disorder treated with atomoxetine. Dev Med Child Neurol 2007;49:498-502.
90. McAfee AT, Holdridge KC, Johannes CB, et al. The effect of pharmacotherapy for attention deficit hyperactivity disorder on risk of seizures in pediatric patients as assessed in an insurance claims database. Curr Drug Saf 2008;3:123-131.
91. McElroy SL, Guerdjikova A, Kotwal R, et al. Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-controlled trial. J Clin Psychiat 2007;68: 390-398.
92. Surman C, Hammerness P, Petty C, et al. Atomoxetine in the treatment of adults with subthreshold and/or late onset attentiondeficit hyperactivity disorder-not otherwise specified (ADHD-NOS): a prospective open-label 6-week study. CNS Neurosci Ther 2010;16:6-12.
93. Sumner CR, Schuh KJ, Sutton VK, et al. Placebo-controlled study of the effects of atomoxetine on bladder control in children with nocturnal enuresis. J Child Adolesc Psychopharm 2006;16:699-711.
94. Desarkar P, Sinha VK. Acute urinary retention associated with atomoxetine use. Aust N Z J Psychiatry 2006;40:936.
95. Humphreys C, Garcia-Bournissen F, Ito S, Koren G. Exposure to attention deficit hyperactivity disorder medications during pregnancy. Can Fam Physician 2007;53:1153-1155.
96. Alessi NE, Spalding S. Atomoxetine and pregnancy. J Am Acad Child Adolesc Psychiat 2003;42:883-884.
97. Heiligenstein J, Michelson D, Wernicke J, et al. Atomoxetine and pregnancy. J Am Acad Child Adolesc Psychiat 2003;42:884-885.