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

Chinese Medicine

Nicola C Savill¹  Chris J Bushe¹ 

[1] Eli Lilly and Company Ltd, Lilly House, Priestley Road, Basingstoke RG24 9NL, United Kingdom

关键词: Methylphenidate;    Atomoxetine;    Systematic review;    Summary of product characteristics;    Suicide-related events;    ADHD;   

Others  :  790938
DOI  :  10.1186/1753-2000-7-19

 received in 2012-11-29, accepted in 2013-06-10,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Bushe and Savill; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]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.
• [2]Center for Disease Control and Prevention (CDC): Attention Deficit Hyperactivity Disorder Among Children Aged 5–17 Years in the United States, 1998–2009. [http://www.cdc.gov/nchs/data/databriefs/db70.pdf webcite]
• [3]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.
• [4]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.
• [5]Hurtig T, Taanila A, Moilanen I, Nordström T, Ebeling H: Nord J Psychiatry. 2012, 66(5):320-328.
• [6]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.
• [7]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.
• [8]Scottish Intercollegiate Guidelines Network: Management of attention deficit and hyperkinetic disorders in children and young people. A nat clin guid(number 112) 2009 [http://www.sign.ac.uk/pdf/sign112.pdf webcite]
• [9]NICE Clinical Guidelines: Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults. [http://www.nice.org.uk/nicemedia/pdf/CG72NiceGuidelinev3.pdf webcite]
• [10]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.
• [11]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. BioMed Central Full Text
• [12]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.
• [13]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.
• [14]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.
• [15]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.
• [16]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.
• [17]U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER): Guidance for Industry Suicidality: Prospective Assessment of Occurrence in Clinical Trials. [http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM225130.pdf webcite]
• [18]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.
• [19]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.
• [20]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.
• [21]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.
• [22]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.
• [23]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.
• [24]Datapharm Communications Limited Electronic Medicines Compendium: Strattera. [http://www.medicines.org.uk/EMC/medicine/14482/SPC/Strattera webcite++10mg%2c+18mg%2c+25mg%2c+40mg%2c+60mg+or+80mg+hard+capsules]
• [25]Datapharm Communications Limited Electronic Medicines Compendium: Concerta. [http://www.medicines.org.uk/EMC/medicine/8382/SPC/Concerta+XL+18+mg+−+36+mg+prolonged+release+tablets/ webcite]
• [26]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.
• [27]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.
• [28]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.
• [29]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]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.
• [31]Coghill D: Pragmatic measures in paediatric psychopharmacology–are we getting it right? Eur Neuropsychopharmacol 2011, 21:571-583.
• [32]Barbaresi WJ, Colligan RC, Weaver AL, Voigt RG, Killian JM, Katusic SK: Pediatrics. 2013, 131(4):637-644.
• [33]James A: Completed suicide, ideation and attempts in attention deficit hyperactivity disorder. Acta Psychiatr Scand 2012, 125:91-92.