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Atomoxetine

Classification: A

Drug products: Atomoxetin Actavis, Atomoxetin Ebb, Atomoxetin Glenmark, Atomoxetin Medical Valley, Atomoxetin Mylan, Atomoxetin Orion, Atomoxetine Accord, Atomoxetine Sandoz, Atomoxetine STADA, Audalis, Strattera

ATC code: N06BA09

Substances: atomoxetine, atomoxetine hydrochloride

Summary

Atomoxetine has been shown to improve ADHD-related difficulties and increase quality of life in both boys and girls. However, meta-analyses have shown atomoxetine to reduce ADHD-symptoms more among girls than boys.

The lowest effective dose should always be used. Despite the identified sex differences, there is generally no reason to differentiate treatment between boys/men and girls/women.

Additional information

In children and adolescents, Attention Deficit Hyperactivity Disorder (ADHD) is more commonly diagnosed in boys, with the sex ratio ranging from 2:1 to 10:1 [1-4], with higher male-to-female ratios found in clinical versus population-based samples. The male-to-female ratio is smaller in adult clinical samples than in childhood and adolescent samples [5]. In women, hyperactivity/impulsivity and conduct problems were stronger predictors of clinical diagnosis and prescriptions of pharmacological treatment, compared to men [6]. Girls more often than boys have ADHD with mainly attention deficit disorder and more rarely clear hyperactivity/impulsivity problems. Therefore, the diagnosis in girls/women may be more difficult to recognize and be less likely to receive pharmacological treatment, and males with ADHD are more likely to receive ADHD medication than females with ADHD [6-9].

Pharmacokinetics and dosing

No differences in atomoxetine pharmacokinetics have been seen between boys/men and girls/women, and no sex differentiation in dosing has been recommended by the pharmaceutical company [10].

Effects

Even though earlier studies of ADHD treatment included few females, recent RCTs to demonstrate efficacy in the newer ER preparations have enrolled reasonable numbers of females [11].

A meta-analysis of nine studies including 1150 patients on atomoxetine and 678 patients on placebo (sex ratio not specified) evaluating efficacy and safety of atomoxetine in children and adolescents showed that male sex was associated with a smaller reduction in ADHD symptoms. This suggests that atomoxetine may be more efficacious in female ADHD patients [12].

Long-term response to atomoxetine in adult ADHD was analyzed in a double-blind trial followed by a three-year open-label study (247 men, 137 women). During the double-blind phase, patient’s sex had an impact on treatment effect. Women showed the greatest difference in improvement versus men on emotional dysregulation. In the end on the open-label phase, women had greater improvement on the hyperactivity/impulsivity section of both outcome measure scales WRAADDS and CAARS [13].

Pooled data from five atomoxetine clinical trials (658 boys, 136 girls) showed that atomoxetine was effective in improving some aspects of patient-reported HR-QoL (health-related quality of life) in both sexes. Patient’s sex did not influence treatment outcome [14]. Also, another study (338 boys, 83 girls) showed that atomoxetine improved ADHD-related difficulties (and hence the quality of life) as perceived by patients, parents and physicians was similar in boys and girls [15].

Adverse effects

When dose-dependent effects of atomoxetine on the corrected QT interval (QTc) was examined in Japanese adult ADHD patients (26 men, 15 women), there was a positive correlation between atomoxetine dosage and prolongation of QTc only in women. There was no correlation between plasma concentrations of atomoxetine and the QTc in either women or men [16].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Updated: 2021-01-26

Date of litterature search: 2020-10-21

References

  1. Nøvik TS, Hervas A, Ralston SJ, Dalsgaard S, Rodrigues Pereira R, Lorenzo MJ et al. Influence of gender on attention-deficit/hyperactivity disorder in Europe--ADORE. Eur Child Adolesc Psychiatry. 2006;15 Suppl 1:I15-24. PubMed
  2. Ramtekkar UP, Reiersen AM, Todorov AA, Todd RD. Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11. J Am Acad Child Adolesc Psychiatry. 2010;49(3):217-28e1-3. PubMed
  3. Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics. 2012;9(3):490-9. PubMed
  4. Gaub M, Carlson CL. Gender differences in ADHD: a meta-analysis and critical review. J Am Acad Child Adolesc Psychiatry. 1997;36(8):1036-45. PubMed
  5. Biederman J, Faraone SV, Monuteaux MC, Bober M, Cadogen E. Gender effects on attention-deficit/hyperactivity disorder in adults, revisited. Biol Psychiatry. 2004;55(7):692-700. PubMed
  6. Mowlem FD, Rosenqvist MA, Martin J, Lichtenstein P, Asherson P, Larsson H. Sex differences in predicting ADHD clinical diagnosis and pharmacological treatment. Eur Child Adolesc Psychiatry. 2019;28(4):481-489. PubMed
  7. Socialstyrelsen. Stöd till barn, ungdomar och vuxna med adhd. Socialstyrelsen.
  8. Mowlem F, Agnew-Blais J, Taylor E, Asherson P. Do different factors influence whether girls versus boys meet ADHD diagnostic criteria? Sex differences among children with high ADHD symptoms. Psychiatry Res. 2019;272:765-773. PubMed
  9. Kok FM, Groen Y, Fuermaier ABM, Tucha O. The female side of pharmacotherapy for ADHD-A systematic literature review. PLoS One. 2020;15(9):e0239257. PubMed
  10. STRATTERA (atomoxetine). DailyMed [www]. U.S National Library of Medicine. [updated 2020-02-25, cited 2020-10-21]. länk
  11. Cornforth C, Sonuga-Barke E, Coghill D. Stimulant drug effects on attention deficit/hyperactivity disorder: a review of the effects of age and sex of patients. Curr Pharm Des. 2010;16:2424-33. PubMed
  12. Cheng JY, Chen RY, Ko JS, Ng EM. Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents-meta-analysis and meta-regression analysis. Psychopharmacology (Berl). 2007;194:197-209. PubMed
  13. Marchant BK, Reimherr FW, Halls C, Williams ED, Strong RE, Kondo D et al. Long-term open-label response to atomoxetine in adult ADHD: influence of sex, emotional dysregulation, and double-blind response to atomoxetine. Atten Defic Hyperact Disord. 2011;3:237-44. PubMed
  14. Wehmeier PM, Schacht A, Escobar R, Hervas A, Dickson R. Health-related quality of life in ADHD: a pooled analysis of gender differences in five atomoxetine trials. Atten Defic Hyperact Disord. 2012;4:25-35. PubMed
  15. Wehmeier PM, Schacht A, Dittmann RW, Banaschewski T. Minor differences in ADHD-related difficulties between boys and girls treated with atomoxetine for attention-deficit/hyperactivity disorder. Atten Defic Hyperact Disord. 2010;2:73-85. PubMed
  16. Suzuki Y, Tajiri M, Sugimoto A, Orime N, Hayashi T, Egawa J et al. Sex Differences in the Effect of Atomoxetine on the QT Interval in Adult Patients With Attention-Deficit Hyperactivity Disorder. J Clin Psychopharmacol. 2017;37(1):27-31. PubMed
  17. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Diana Rydberg, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson