Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-26T03:12:07.476Z Has data issue: false hasContentIssue false
  • English
  • Français

Use of atomoxetine and suicidal ideation in children and adolescents: Results of an observational cohort study within general practice in England

Published online by Cambridge University Press:  23 March 2020

M. Davies ,
A. Coughtrie ,
D. Layton  and
S.A.S. Shakir
M. Davies*
Affiliation:
Drug safety research unit, Bursledon hall, Blundell lane, SO31 1AASouthampton, United Kingdom University of Portsmouth, PortsmouthUnited Kingdom
A. Coughtrie
Affiliation:
Drug safety research unit, Bursledon hall, Blundell lane, SO31 1AASouthampton, United Kingdom
D. Layton
Affiliation:
Drug safety research unit, Bursledon hall, Blundell lane, SO31 1AASouthampton, United Kingdom University of Portsmouth, PortsmouthUnited Kingdom
S.A.S. Shakir
Affiliation:
Drug safety research unit, Bursledon hall, Blundell lane, SO31 1AASouthampton, United Kingdom University of Portsmouth, PortsmouthUnited Kingdom
*
*Corresponding author. Drug safety research unit, Bursledon hall, Blundell lane, Southampton, SO31 1AA, United Kingdom. Tel.: +44 0 23 8040 8600; fax: +44 0 23 8040 8609. E-mail address:[email protected] (M. Davies).
Get access

Abstract

Aim

To investigate the association between atomoxetine, a drug used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and suicidal ideation, within a cohort of 2–18-year-old patients in England.

Methods

The study was conducted using the observational cohort technique of Modified prescription event monitoring (M-PEM). Patients prescribed atomoxetine were identified from dispensed prescriptions issued by primary care physicians. A customised postal GP questionnaire was used to capture outcome data for suicidal ideation. A matched pair cohort analysis was performed within patients to compare the risk of suicidal ideation in the period after starting atomoxetine with the risk prior to starting atomoxetine; this was stratified by age and concomitant use of methylphenidate. Additional information on patient characteristics, and events of interest was also collected; individual cases of suicidal ideation were qualitatively assessed for drug relatedness.

Results

Of the final cohort (n = 4509); 85.5% male (n = 3857), median age 11 years (IQR: 9,14). Primary prescribing indication for atomoxetine was ADHD (n = 4261, 94.6%). Almost a quarter of the cohort had been co-prescribed methylphenidate. Results of the matched pair cohort analysis indicated that the period after starting atomoxetine was not associated with an increase in the incidence of suicidal ideation compared to the period prior to starting treatment (RR: 0.71; CI: 0.48–1.07; P-value: 0.104). Individual case assessment of suicidal ideation suggested a causal association within a number of cases.

Conclusions

This study found no evidence of an increased risk of suicidal ideation during treatment with atomoxetine, compared to the period prior to starting treatment. Amongst age specific subgroups, this risk may change. Nonetheless, individual case assessment suggested a causal relationship in some patients, hence physicians need to be aware of the possibility of developing this event, and furthermore consider how best to detect it in this paediatric population. This study demonstrates the importance of combining quantitative statistical analyses with a qualitative case series assessment.

Keywords

Attention deficit disorder with hyperactivityAtomoxetineSuicidal ideationDrug-related side effects and adverse reactionsDrug utilisation
Type
Original article
Information
European Psychiatry , Volume 39 , January 2017 , pp. 11 - 16
Copyright
Copyright © Elsevier Masson SAS 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bushe, CJSavill, NAtomoxetine in children and adolescents with attention-deficit/hyperactivity disorder. Systematic review of review papers 2009–2011. An update for clinicians. J Cent Nerv Syst Dis 2011; 3: 209–217.CrossRefGoogle ScholarPubMed
Capuano, AScavone, CRafaniello, CArcieri, RRossi, FPanei, PAtomoxetine in the treatment of attention deficit hyperactivity disorder and suicidal ideation. Expert Opin Drug Saf 2014; 13(Suppl. 1): S69–S78.CrossRefGoogle ScholarPubMed
Bangs, MEWietecha, LAWang, SBuchanan, ASKelsey, DKMeta-analysis of suicide-related behavior or ideation in child, adolescent, and adult patients treated with atomoxetine. J Child Adolesc Psychopharmacol 2014CrossRefGoogle ScholarPubMed
Chen, QSjolander, ARuneson, BD’Onofrio, BMLichtenstein, PLarsson, HDrug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study. BMJ 2014;348:g3769.CrossRefGoogle ScholarPubMed
Cavazzoni P. Eli Lilly & Co. 120905PC. Analyses of suicide-related events in the pediatric and adult population treated with atomoxetine [Ref. type: generic].Google Scholar
Bangs, MEJin, LZhang, SDesaiah, DAllen, AJRead, HAet al.Hepatic events associated with atomoxetine treatment for attention-deficit hyperactivity disorder. Drug Saf 2008; 31(4): 345–354.CrossRefGoogle ScholarPubMed
Singh, SLoke, YKDrug safety assessment in clinical trials: methodological challenges and opportunities. Trials 2012;13:138.CrossRefGoogle ScholarPubMed
McCarthy, SCranswick, NPotts, LTaylor, EWong, ICMortality 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(11): 1089–1096.CrossRefGoogle Scholar
Ruggiero, SRafaniello, CBravaccio, CGrimaldi, GGranato, RPascotto, Aet al.Safety of attention-deficit/hyperactivity disorder medications in children: an intensive pharmacosurveillance monitoring study. J Child Adolesc Psychopharmacol 2012; 22(6): 415–422.CrossRefGoogle ScholarPubMed
Paxton, GACranswick, NEAcute suicidality after commencing atomoxetine. J Paediatr Child Health 2008; 44(10): 596–598.CrossRefGoogle ScholarPubMed
Markx, SKahn, DAAn 18-year-old woman with new-onset suicidal ideation while being treated with atomoxetine. J Psychiatr Pract 2008; 14(1): 62–66.CrossRefGoogle ScholarPubMed
Cummings, PMcKnight, BWeiss, NSMatched-pair cohort methods in traffic crash research. Accid Anal Prev 2003; 35(1): 131–141.CrossRefGoogle ScholarPubMed
Layton, DHazell, LShakir, SAWModified prescription-event monitoring studies; a tool for pharmacovigilance and risk management. Drug Saf 2011CrossRefGoogle ScholarPubMed
Cavazzoni P. Eli Lilly & Co. 120905PC. Analyses of suicide-related events in the pediatric and adult population treated with atomoxetine. [Ref. type: generic].Google Scholar
Machin, DCampbell, MFayers, Pet al.Sample size tables for clinical studies. Table 7. 2. Oxford, UK: Blackwell Science Ltd; 1997.Google Scholar
Council for international organizations of medical sciences (CIOMS), World health organisation (WHO). International ethical guidelines for biomedical research involving human subjects [online]; 2002 [Geneva, Switzerland], http://www.cioms.ch/publications/layout_guide2002.pdf.Google Scholar
Royal college of physicians. Guidelines on the practice of ethics committees in medical research with human participants, 4th ed., London: Royal College of Physicians of London; 2007 [3rd ed.].Google Scholar
British medical association board of science, British medical association science & education. Reporting adverse drug reactions. A guide for healthcare professionals [online]; 2006 [London, UK], http://bmaopac.hosted.exlibrisgroup.com/exlibris/aleph/a21_1/apache_media/GYVFNJ1RT2PFNDUJ8IUKPUNTFVRF8G.pdf.Google Scholar
Health research authority. Confidentiality advisory group advice and approval decisions. Prescription-event monitoring. CAG ref: ECC 5-07(b)/2009; 2015 [Ref. type: generic].Google Scholar
General medical council. Confidentiality booklet; 2009 [Ref. type: generic].Google Scholar
General medical council. Confidentiality: disclosing information for education and training purposes; 2009 [Date accessed: 11/07/2011], http://www.gmc-uk.org/Confidentiality_disclosing_info_education_2009.pdf_27493403.pdf.Google Scholar
ICH harmonised tripartite guideline. Clinical investigation of medicinal products in the paediatric population E11; 2000 [Ref. type: generic].Google Scholar
Shakir, SCausality and correlation in pharmacovigilance. In: Talbot, JWaller, P editors. Stephens’ detection of new adverse drug reactions, 5 ed., Chichester: John Wiley & Sons Ltd; 2004. p. 329–343.Google Scholar
Food and drug administration. Strattera (atomoxetine), september 2005 – labelling revision; 2005 [Ref. type: generic].Google Scholar
McAvoy, BRKaner, EFGeneral practice postal surveys: a questionnaire too far?. BMJ 1996; 313(7059): 732–733.CrossRefGoogle ScholarPubMed
Heeley, ERiley, JLayton, DWilton, LVShakir, SAPrescription-event monitoring and reporting of adverse drug reactions. Lancet 2001; 358(9296): 1872–1873.CrossRefGoogle ScholarPubMed
Martin, RMKapoor, KVWilton, LVMann, RDUnderreporting of suspected adverse drug reactions to newly marketed (“black triangle”) drugs in general practice: observational study. BMJ 1998; 317(7151): 119–120.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.