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Published in: Child and Adolescent Psychiatry and Mental Health 1/2013

Open Access 01-12-2013 | Research

Suicide related events and attention deficit hyperactivity disorder treatments in children and adolescents: a meta-analysis of atomoxetine and methylphenidate comparator clinical trials

Authors: Chris J Bushe, Nicola C Savill

Published in: Child and Adolescent Psychiatry and Mental Health | Issue 1/2013

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Abstract

Background

Attention Deficit Hyperactivity Disorder (ADHD) is becoming an increasingly commonly diagnosed and treated childhood illness. Untreated ADHD is recognised as an independent risk factor for suicide-related events and deliberate self-harm and is reported more commonly in these populations. With the treatment of ADHD it is thus crucial to understand further any associations between pharmacological treatments and suicide-related events. Specific data for suicide-related events with stimulants have not been publically reported. Suicidal tendencies are, however, a contraindication to the treatment of patients with methylphenidate. Clinicians and patients may be helped by a meta-analytic comparison of suicide-related events in comparative randomised double-blind atomoxetine and methylphenidate clinical trials.

Methods

Suicide-related events retrospectively mapped to the suicide-related event assessment instrument recommended by the FDA, the Columbia Classification Algorithm for Suicide Assessment (C-CASA), were evaluated in five double-blind placebo controlled comparative studies of atomoxetine and methylphenidate (n = 1024) of 6 to 9 weeks duration. The Mantel-Haenszel risk ratio and Mantel-Haenszel incidence differences have been calculated.

Results

In total there were 5 suicide-related events, atomoxetine (ATX) 3/559 and methylphenidate (MPH) 2/465. There were no suicide attempts nor completed suicides. Meta-analysis finds no difference of a difference in risk between ATX and MPH with a Mantel-Haenszel risk ratio of 0.52 (95% CI; 0.06, 4.54).

Conclusion

In the only reported meta-analysis of comparative suicide-related events between atomoxetine and methylphenidate, no significant evidence of a difference in risk has been found. These data may be informative to clinicians and patients when developing clinical guidelines.
Appendix
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Literature
1.
go back to reference McCarthy S, Asherson P, Coghill D, Hollis C, Murray M, Potts L, Sayal K, De Soysa R, Taylor E, Williams T, Wong ICK: Attention-deficit hyperactivity disorder: treatment discontinuation in adolescents and young adults. Br J Psychiatry. 2009, 194: 273-277. 10.1192/bjp.bp.107.045245.CrossRefPubMed McCarthy S, Asherson P, Coghill D, Hollis C, Murray M, Potts L, Sayal K, De Soysa R, Taylor E, Williams T, Wong ICK: Attention-deficit hyperactivity disorder: treatment discontinuation in adolescents and young adults. Br J Psychiatry. 2009, 194: 273-277. 10.1192/bjp.bp.107.045245.CrossRefPubMed
3.
go back to reference Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Döpfner M, Hamilton R, Hollis C, Holtmann M, Hulpke-Wette M, Lecendreux M, Rosenthal E, Rothenberger A, Santosh P, Sergeant J, Simonoff E, Sonuga-Barke E, Wong ICK, Zuddas A, Steinhausen HC, Taylor E: European guidelines group. european guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011, 20: 17-37. 10.1007/s00787-010-0140-6.PubMedCentralCrossRefPubMed Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Döpfner M, Hamilton R, Hollis C, Holtmann M, Hulpke-Wette M, Lecendreux M, Rosenthal E, Rothenberger A, Santosh P, Sergeant J, Simonoff E, Sonuga-Barke E, Wong ICK, Zuddas A, Steinhausen HC, Taylor E: European guidelines group. european guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011, 20: 17-37. 10.1007/s00787-010-0140-6.PubMedCentralCrossRefPubMed
4.
go back to reference James A, Lai F, Dahl C: Attention deficit hyperactivity disorder and suicide: a review of possible associations. Acta Psychiatr Scand. 2004, 110 (6): 408-415. 10.1111/j.1600-0447.2004.00384.x.CrossRefPubMed James A, Lai F, Dahl C: Attention deficit hyperactivity disorder and suicide: a review of possible associations. Acta Psychiatr Scand. 2004, 110 (6): 408-415. 10.1111/j.1600-0447.2004.00384.x.CrossRefPubMed
5.
go back to reference Hurtig T, Taanila A, Moilanen I, Nordström T, Ebeling H: Nord J Psychiatry. 2012, 66 (5): 320-328. 10.3109/08039488.2011.644806.CrossRefPubMed Hurtig T, Taanila A, Moilanen I, Nordström T, Ebeling H: Nord J Psychiatry. 2012, 66 (5): 320-328. 10.3109/08039488.2011.644806.CrossRefPubMed
6.
go back to reference Moran P, Coffey C, Romaniuk H, Olsson C, Borschmann R, Carlin JB, Patton GC: The natural history of self-harm from adolescence to young adulthood: a population-based cohort study. Lancet. 2012, 379: 236-243. 10.1016/S0140-6736(11)61141-0.CrossRefPubMed Moran P, Coffey C, Romaniuk H, Olsson C, Borschmann R, Carlin JB, Patton GC: The natural history of self-harm from adolescence to young adulthood: a population-based cohort study. Lancet. 2012, 379: 236-243. 10.1016/S0140-6736(11)61141-0.CrossRefPubMed
7.
go back to reference Bangs ME, Tauscher-Wisniewski S, Polzer J: Meta-analysis of suicide-related behaviour-events in patients treated with atomoxetine. J Am Acad Child Adolesc Psychiatry. 2008, 47: 209-218. 10.1097/chi.0b013e31815d88b2.CrossRefPubMed Bangs ME, Tauscher-Wisniewski S, Polzer J: Meta-analysis of suicide-related behaviour-events in patients treated with atomoxetine. J Am Acad Child Adolesc Psychiatry. 2008, 47: 209-218. 10.1097/chi.0b013e31815d88b2.CrossRefPubMed
10.
go back to reference Bushe CJ, Savill N: Atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder. systematic review of review papers 2009–2011. An update for clinicians. J Central Nerv Sys Disease. 2011, 3: 209-217.CrossRef Bushe CJ, Savill N: Atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder. systematic review of review papers 2009–2011. An update for clinicians. J Central Nerv Sys Disease. 2011, 3: 209-217.CrossRef
11.
go back to reference Savill N, Bushe CJ: A systematic review of the safety information contained within the summaries of product characteristics of medications licensed in the United Kingdom for attention deficit hyperactivity disorder. How does the safety prescribing advice compare with national guidance?. Child Adolesc Psychiatry Ment Health. 2012, 6: 2-10.1186/1753-2000-6-2.PubMedCentralCrossRefPubMed Savill N, Bushe CJ: A systematic review of the safety information contained within the summaries of product characteristics of medications licensed in the United Kingdom for attention deficit hyperactivity disorder. How does the safety prescribing advice compare with national guidance?. Child Adolesc Psychiatry Ment Health. 2012, 6: 2-10.1186/1753-2000-6-2.PubMedCentralCrossRefPubMed
12.
go back to reference Wolraich M, Brown L, Brown RT, DuPaul G, Earls M, Feldman HM, Ganiats TG, Kaplanek B, Meyer B, Perrin J, Pierce K, Reiff M, Stein MT, Visser SADHD, Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management: Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011, 128: 1007-1022.CrossRefPubMed Wolraich M, Brown L, Brown RT, DuPaul G, Earls M, Feldman HM, Ganiats TG, Kaplanek B, Meyer B, Perrin J, Pierce K, Reiff M, Stein MT, Visser SADHD, Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management: Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011, 128: 1007-1022.CrossRefPubMed
13.
go back to reference Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS: Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter randomized prospective study. Adv Ther. 2005, 22: 498-512. 10.1007/BF02849870.CrossRefPubMed Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS: Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter randomized prospective study. Adv Ther. 2005, 22: 498-512. 10.1007/BF02849870.CrossRefPubMed
14.
go back to reference Didoni A, Sequi M, Panei P, Bonati M, Lombardy: ADHD registry group: One-year prospective follow-up of pharmacological in treatment in children with attention-deficit/hyperactivity disorder. Eur J Clin Pharmacol. 2011, 67: 1061-1067. 10.1007/s00228-011-1050-3.CrossRefPubMed Didoni A, Sequi M, Panei P, Bonati M, Lombardy: ADHD registry group: One-year prospective follow-up of pharmacological in treatment in children with attention-deficit/hyperactivity disorder. Eur J Clin Pharmacol. 2011, 67: 1061-1067. 10.1007/s00228-011-1050-3.CrossRefPubMed
15.
go back to reference Hazell PL, Kohn MR, Dickson R, Walton RJ, Granger RE, van Wyk GW: Core ADHD symptom improvement with atomoxetine versus methylphenidate: a direct comparison meta-analysis. J Atten Disord. 2011, 15: 674-683. 10.1177/1087054710379737.CrossRefPubMed Hazell PL, Kohn MR, Dickson R, Walton RJ, Granger RE, van Wyk GW: Core ADHD symptom improvement with atomoxetine versus methylphenidate: a direct comparison meta-analysis. J Atten Disord. 2011, 15: 674-683. 10.1177/1087054710379737.CrossRefPubMed
16.
go back to reference Posner K, Oquendo MA, Gould M, Stanley B, Davies M: Columbia classification algorithm of suicide assessment (C-CASA): classification of suicidal events in the FDA’s paediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 2007, 164: 1035-1043. 10.1176/appi.ajp.164.7.1035.PubMedCentralCrossRefPubMed Posner K, Oquendo MA, Gould M, Stanley B, Davies M: Columbia classification algorithm of suicide assessment (C-CASA): classification of suicidal events in the FDA’s paediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 2007, 164: 1035-1043. 10.1176/appi.ajp.164.7.1035.PubMedCentralCrossRefPubMed
18.
go back to reference Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ: The Columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011, 168: 1266-1277. 10.1176/appi.ajp.2011.10111704.PubMedCentralCrossRefPubMed Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ: The Columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011, 168: 1266-1277. 10.1176/appi.ajp.2011.10111704.PubMedCentralCrossRefPubMed
19.
go back to reference Spencer TJ, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ: Results from 2 proof of concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002, 63: 1140-1147. 10.4088/JCP.v63n1209.CrossRefPubMed Spencer TJ, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ: Results from 2 proof of concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002, 63: 1140-1147. 10.4088/JCP.v63n1209.CrossRefPubMed
20.
go back to reference Sangal RB, Owens J, Allen AJ, Sutton V, Schuh K, Kelsey D: Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Sleep. 2006, 29: 1573-1585.PubMed Sangal RB, Owens J, Allen AJ, Sutton V, Schuh K, Kelsey D: Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Sleep. 2006, 29: 1573-1585.PubMed
21.
go back to reference Newcorn J, Kratochvil C, Allen A, Casat C, Ruff D, Moore R: Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008, 165: 721-730. 10.1176/appi.ajp.2007.05091676.CrossRefPubMed Newcorn J, Kratochvil C, Allen A, Casat C, Ruff D, Moore R: Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008, 165: 721-730. 10.1176/appi.ajp.2007.05091676.CrossRefPubMed
22.
go back to reference Wang Y, Zheng Y, Du Y, Song DH, Shin YJ, Cho S, Kim B, Ahn D, Marquez-Caraveo M, Gao H, Williams D, Levine L: Atomoxetine versus methylphenidate in paediatric outpatients with attention deficit hyperactivity disorder: a randomized double-blind comparison trial. Aust N Z J Psychiatry. 2007, 41: 222-230. 10.1080/00048670601057767.CrossRefPubMed Wang Y, Zheng Y, Du Y, Song DH, Shin YJ, Cho S, Kim B, Ahn D, Marquez-Caraveo M, Gao H, Williams D, Levine L: Atomoxetine versus methylphenidate in paediatric outpatients with attention deficit hyperactivity disorder: a randomized double-blind comparison trial. Aust N Z J Psychiatry. 2007, 41: 222-230. 10.1080/00048670601057767.CrossRefPubMed
23.
go back to reference Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann R, Graham J, Taylor E, Sergeant J, European ADHD: Guidelines group. practitioner review : current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J Child Psychol Psychiatry. 2013, 54: 227-246. 10.1111/jcpp.12036.CrossRefPubMed Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann R, Graham J, Taylor E, Sergeant J, European ADHD: Guidelines group. practitioner review : current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J Child Psychol Psychiatry. 2013, 54: 227-246. 10.1111/jcpp.12036.CrossRefPubMed
26.
go back to reference McCarthy S, Cranswick N, Potts L, Taylor E, Wong ICK: 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. 10.2165/11317630-000000000-00000.CrossRefPubMed McCarthy S, Cranswick N, Potts L, Taylor E, Wong ICK: 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. 10.2165/11317630-000000000-00000.CrossRefPubMed
27.
go back to reference Schelleman H, Bilker W, Strom B, Kimmel S, Newcom C, Guevara J, Daniel G, Cziraky M, Hennessy S: Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011, 127: 1102-1110. 10.1542/peds.2010-3371.PubMedCentralCrossRefPubMed Schelleman H, Bilker W, Strom B, Kimmel S, Newcom C, Guevara J, Daniel G, Cziraky M, Hennessy S: Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011, 127: 1102-1110. 10.1542/peds.2010-3371.PubMedCentralCrossRefPubMed
28.
go back to reference Thurstone C, Riggs PD, Salomonsen-Sautel S, Mikulich-Gilbertson SK: Randomized, 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.PubMedCentralPubMed Thurstone C, Riggs PD, Salomonsen-Sautel S, Mikulich-Gilbertson SK: Randomized, 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.PubMedCentralPubMed
29.
go back to reference Davies M, Cornelius V, Fogg C, Wilton L, Shakir S: A study to examine events of suicidal ideation in patients prescribed atomoxetine in England. Drug Saf. 2009, 32: 976. Davies M, Cornelius V, Fogg C, Wilton L, Shakir S: A study to examine events of suicidal ideation in patients prescribed atomoxetine in England. Drug Saf. 2009, 32: 976.
30.
go back to reference Donnelly C, Bangs M, Trzepacz P, Jin L, Zhang S, Witte MM, Ball SG, Spencer TJ: Safety and tolerability of atomoxetine over 3 to 4 years in children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry. 2009, 48: 176-185. 10.1097/CHI.0b013e318193060e.CrossRefPubMed Donnelly C, Bangs M, Trzepacz P, Jin L, Zhang S, Witte MM, Ball SG, Spencer TJ: Safety and tolerability of atomoxetine over 3 to 4 years in children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry. 2009, 48: 176-185. 10.1097/CHI.0b013e318193060e.CrossRefPubMed
31.
go back to reference Coghill D: Pragmatic measures in paediatric psychopharmacology–are we getting it right?. Eur Neuropsychopharmacol. 2011, 21: 571-583. 10.1016/j.euroneuro.2010.11.007.CrossRefPubMed Coghill D: Pragmatic measures in paediatric psychopharmacology–are we getting it right?. Eur Neuropsychopharmacol. 2011, 21: 571-583. 10.1016/j.euroneuro.2010.11.007.CrossRefPubMed
33.
go back to reference James A: Completed suicide, ideation and attempts in attention deficit hyperactivity disorder. Acta Psychiatr Scand. 2012, 125: 91-92. 10.1111/j.1600-0447.2011.01775.x.CrossRefPubMed James A: Completed suicide, ideation and attempts in attention deficit hyperactivity disorder. Acta Psychiatr Scand. 2012, 125: 91-92. 10.1111/j.1600-0447.2011.01775.x.CrossRefPubMed
Metadata
Title
Suicide related events and attention deficit hyperactivity disorder treatments in children and adolescents: a meta-analysis of atomoxetine and methylphenidate comparator clinical trials
Authors
Chris J Bushe
Nicola C Savill
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Child and Adolescent Psychiatry and Mental Health / Issue 1/2013
Electronic ISSN: 1753-2000
DOI
https://doi.org/10.1186/1753-2000-7-19

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