BMJ  2004;328:879-883 (10 April), doi:10.1136/bmj.328.7444.879

Clinical review

Efficacy and safety of antidepressants for children and adolescents

¹ Department of Psychological Medicine, Women's and Children's Hospital, North Adelaide, 5006 SA, Australia, ² Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, Adelaide, 5000 SA, ³ Department of General Practice, University of Adelaide, Adelaide, 5005 SA, ⁴ Department of Clinical and Experimental Pharmacology, University of Adelaide, ⁵ Health Surveillance and Evaluation Section, Public Health, Department of Human Services, Melbourne, 3000 Vic, Australia, ⁶ University of Wales Academic Unit, Wrexham LL13 7YP

How safe and effective are antidepressants in children and adolescents? The authors of this review have found disturbing shortcomings in the methods and reporting of trials of newer antidepressants in this patient group

The first 150 words of the full text of this article appear below.

Introduction

Antidepressants introduced since 1990, especially selective serotonin reuptake inhibitors and venlafaxine, have been used increasingly as first line treatment for depression in children.^{1 2} The safety of prescribing antidepressants to children (including adolescents) has been the subject of increasing concern in the community and the medical profession, leading to recommendations against their use from government and industry (box 1). In this paper, we review the published literature on the efficacy and safety of newer antidepressants in children.

Methods

Having criticised the way in which Keller et al interpreted the results of their study,^{3 4} we sought to check the quality of methods and reporting of other published trials of newer antidepressants in children (box 2). Of seven published randomised controlled trials of newer antidepressants for depressed children published in refereed journals, six used a placebo control.^{3 5-9} We analysed each study's methods and the extent to which authors' conclusions were supported by data. The . . . [Full text of this article]

Funding of trials

Efficacy

Adverse effects of treatment

Study methods

Withdrawals
Use of categorical outcomes
Unblinding
Doubtful clinical implications of statistical superiority to placebo

Quality of reporting

Conclusion

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Articles

Should young people be given antidepressants? Yes

Andrew Cotgrove
BMJ 2007 335: 750. [Extract] [Full Text] [PDF]

Should young people be given antidepressants? No

Sami Timimi
BMJ 2007 335: 751. [Extract] [Full Text] [PDF]

Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1)

Karmela Krleza-Jeric, An-Wen Chan, Kay Dickersin, Ida Sim, Jeremy Grimshaw, Christian Gluud for the Ottawa Group
BMJ 2005 330: 956-958. [Extract] [Full Text] [PDF]

TADS study raises concerns

Jon Jureidini, Anne Tonkin, and Peter R Mansfield
BMJ 2004 329: 1343-1344. [Extract] [Full Text]

Should antidepressants be used in children?
BMJ 2004 328: 0. [Full Text] [PDF]

Inappropriate admission of young people with mental disorder to adult psychiatric wards and paediatric wards: cross sectional study of six months' activity

Adrian Worrall, Anne O'Herlihy, Sube Banerjee, Tony Jaffa, Paul Lelliott, Peter Hill, Angela Scott, and Helen Brook
BMJ 2004 328: 867. [Full Text] [PDF]

This article has been cited by other articles:

• Tsapakis*, E. M., Soldani*, F., Tondo, L., Baldessarini, R. J. (2008). Efficacy of antidepressants in juvenile depression: meta-analysis. Br. J. Psychiatry 193: 10-17 [Abstract] [Full text]  
• Olfson, M., Marcus, S. C., Druss, B. G. (2008). Effects of Food and Drug Administration Warnings on Antidepressant Use in a National Sample. Arch Gen Psychiatry 65: 94-101 [Abstract] [Full text]  
• Timimi, S. (2008). Child psychiatry and its relationship with the pharmaceutical industry: theoretical and practical issues. Adv. Psychiatr. Treat. 14: 3-9 [Abstract] [Full text]  
• Cheung, A. H., Zuckerbrot, R. A., Jensen, P. S., Ghalib, K., Laraque, D., Stein, R. E.K., and the GLAD-PC Steering Group, (2007). Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and Ongoing Management. Pediatrics 120: e1313-e1326 [Abstract] [Full text]  
• Cotgrove, A. (2007). Should young people be given antidepressants? Yes. BMJ 335: 750-750 [Full text]  
• Timimi, S. (2007). Should young people be given antidepressants? No. BMJ 335: 751-751 [Full text]  
• The TADS Team, (2007). The Treatment for Adolescents With Depression Study (TADS): Long-term Effectiveness and Safety Outcomes. Arch Gen Psychiatry 64: 1132-1143 [Abstract] [Full text]  
• Luty, J., Umoh, O., Sessay, M., Sarkhel, A. (2007). Effectiveness of Changing Minds campaign factsheets in reducing stigmatised attitudes towards mental illness. Psychiatr. Bull. 31: 377-381 [Abstract] [Full text]  
• DUBICKA, B., HADLEY, S., ROBERTS, C. (2006). Suicidal behaviour in youths with depression treated with new-generation antidepressants: Meta-analysis. Br. J. Psychiatry 189: 393-398 [Abstract] [Full text]  
• Thomas, C. P., Conrad, P., Casler, R., Goodman, E. (2006). Trends in the Use of Psychotropic Medications Among Adolescents, 1994 to 2001. Psychiatr. Serv. 57: 63-69 [Abstract] [Full text]  
• Simon, G. E., Savarino, J., Operskalski, B., Wang, P. S. (2006). Suicide Risk During Antidepressant Treatment. Am. J. Psychiatry 163: 41-47 [Abstract] [Full text]  
• Cipriani, A. (2005). Forensic database study suggests selective serotonin reuptake inhibitors do not increase the risk of suicide in people taking antidepressants. Evid. Based Ment. Health 8: 113-113 [Full text]  
• TONKIN, A., JUREIDINI, J. (2005). Wishful thinking: antidepressant drugs in childhood depression. Br. J. Psychiatry 187: 304-305 [Full text]  
• Leslie, L. K., Newman, T. B., Chesney, P. J., Perrin, J. M. (2005). The Food and Drug Administration's Deliberations on Antidepressant Use in Pediatric Patients. Pediatrics 116: 195-204 [Abstract] [Full text]  
• Dubicka, B., Goodyer, I. (2005). Should we prescribe antidepressants to children?. Psychiatr. Bull. 29: 164-167 [Full text]  
• Krleza-Jeric, K., Chan, A.-W., Dickersin, K., Sim, I., Grimshaw, J., Gluud, C., for the Ottawa Group, (2005). Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1). BMJ 330: 956-958 [Full text]  
• Steer, C R (2005). Managing attention deficit/hyperactivity disorder: unmet needs and future directions. Arch. Dis. Child. 90: i19-i25 [Abstract] [Full text]  
• Timimi, S. (2004). Rethinking childhood depression. BMJ 329: 1394-1396 [Full text]  
• Jureidini, J., Tonkin, A., Mansfield, P. R (2004). TADS study raises concerns. BMJ 329: 1343-1344 [Full text]  
• Murray, M L, de Vries, C S, Wong, I C K (2004). A drug utilisation study of antidepressants in children and adolescents using the General Practice Research Database. Arch. Dis. Child. 89: 1098-1102 [Abstract] [Full text]  
• (2004). Other articles noted. Evid. Based Ment. Health 7: 100-100 [Full text]  
• (2004). Lucina. Arch. Dis. Child. 89: 1080-1080 [Full text]  
• Marcovitch, H. (2004). Use of stimulants for attention deficit hyperactivity disorder: AGAINST. BMJ 329: 908-909 [Full text]  
• Cohen, J. S (2004). Antidepressants: An Avoidable and Solvable Controversy. The Annals of Pharmacotherapy 38: 1743-1746 [Full text]  
• (2004). Other articles noted. Evid. Based Med. 9: e5-e5 [Full text]  
• (2004). Other articles noted. Evid. Based Med. 9: 159-160 [Full text]  
• Conrad, P. (2004). Prescribing More Psychotropic Medications for Children: What Does the Increase Mean?. Arch Pediatr Adolesc Med 158: 829-830 [Full text]  
• Rosack, J. (2004). Clinical Trials Controversy Spotlights Flawed System. Psychiatr. News 39: 1-45 [Full text]  
• (2004). SSRIs: Reconsidering Their Role in Childhood Depression. JWatch Psychiatry 2004: 8-8 [Full text]  
• Garland, E. J. (2004). SSRI treatment for under-18s. CMAJ 170: 1772-1772 [Full text]  
• Herxheimer, A., Mintzes, B. (2004). SSRI treatment for under-18s. CMAJ 170: 1771-1772 [Full text]  
• (2004). SSRIs: Reconsidering Their Role in Childhood Depression. JWatch General 2004: 3-3 [Full text]  

Rapid Responses:

Read all Rapid Responses

Flawed reasoning in critique of child antidepressant trials

Nicholas A. DeMartinis
bmj.com, 10 Apr 2004 [Full text]

The quality of logical reasoning used in attacking an opponent's argument

Jeffrey Mann
bmj.com, 11 Apr 2004 [Full text]

Juredini et al use misleading evidence to support their claims

David M Foreman
bmj.com, 11 Apr 2004 [Full text]

Flawed conclusions

Mark Berelowitz
bmj.com, 12 Apr 2004 [Full text]

An important debate

John F Corish
bmj.com, 12 Apr 2004 [Full text]

What is the signal/noise ratio of antidepressant drug RCTs in children?

Jeffrey Mann
bmj.com, 13 Apr 2004 [Full text]

Most of the studies are underpowered: a meta-analysis is needed.

Christopher K Gale
bmj.com, 13 Apr 2004 [Full text]

Service to Humanity

Grace E Jackson
bmj.com, 13 Apr 2004 [Full text]

Caution: to avoid throwing the baby with the bath water

L Duvika Mewasingh
bmj.com, 16 Apr 2004 [Full text]

The Utility of Antidepressants in Pediatric Depression

Sanjeev Pathak
bmj.com, 17 Apr 2004 [Full text]

Another example of illogical reasoning and the non-provision of EBM evidence

Jeffrey Mann
bmj.com, 18 Apr 2004 [Full text]

How do the parents of adolescents and children make sensible decisions now?

Malcolm VandenBurg, et al.
bmj.com, 19 Apr 2004 [Full text]

Adolescent depression - what do you do when treatment doesn't work?

Andrew F Clark
bmj.com, 20 Apr 2004 [Full text]

Conclusions not applicable to severe adolescent depression

Bernadka W. Dubicka
bmj.com, 20 Apr 2004 [Full text]

Sertraline Pediatric Depression Trial Met Highest Standards of Study Design and Reporting

Cathryn M Clary, et al.
bmj.com, 27 Apr 2004 [Full text]

Everybody has an agenda

Chris. L. Manning
bmj.com, 30 Apr 2004 [Full text]

What's your agenda?

Alan G. Wade, et al.
bmj.com, 3 May 2004 [Full text]

What's your agenda/everybody has an agenda - further examples of illogical reasoning

Jeffrey Mann
bmj.com, 4 May 2004 [Full text]

CSM warning on risperidone and olanzapine: who takes the risks when patients lack capacity?

Donald H R Mowat, et al.
bmj.com, 4 May 2004 [Full text]

Depression in children and adolescents: Diagnostic and treatment perspectives!

Dr. Naseem A. Qureshi
bmj.com, 5 May 2004 [Full text]

What is the definition of "clinical significance"

Jeffrey Mann
bmj.com, 6 May 2004 [Full text]

declaration of interests

Grace E Jackson
bmj.com, 17 Aug 2004 [Full text]

Response to Pfizer

Peter R Mansfield
bmj.com, 27 Jun 2005 [Full text]