Skip to main content
×
×
Home

Efficacy of antidepressants in juvenile depression: meta-analysis

  • Evangelia M. Tsapakis (a1), Federico Soldani (a2), Leonardo Tondo (a3) and Ross J. Baldessarini (a4)
Abstract
Background

The safety of antidepressants in children and adolescents is being questioned and the efficacy of these drugs in juvenile depression remains uncertain

Aims

To assess antidepressant efficacy in juvenile depression

Method

Systematic review and meta-analysis of randomised controlled trials (RCTs) comparing responses to antidepressants, overall and by type, v. placebo in young people with depression

Results

Thirty drug-placebo contrasts in RCTs lasting 8 weeks (median) involved 3069 participants (512 person-years) of average age 13.5 years. Meta-analysis yielded a modest pooled drug/placebo response rate ratio (RR=1.22, 95% CI 1.15–1.31), with little separation between antidepressant types. Findings were similar for response rate differences and corresponding number needed to treat (NNT): overall NNT=9; tricyclic antidepressants NNT=14 > serotonin reuptake inhibitors NNT=9 > other antidepressants NNT=8. Numbers needed to treat decreased with increasing age: children (NNT=21) > mixed ages (NNT=10) > adolescents (NNT=8)

Conclusions

Antidepressants of all types showed limited efficacy in juvenile depression, but fluoxetine might be more effective, especially in adolescents. Studies in children and in severely depressed, hospitalised or suicidal juvenile patients are needed, and effective, safe and readily accessible treatments for juvenile depression are urgently required

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Efficacy of antidepressants in juvenile depression: meta-analysis
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Efficacy of antidepressants in juvenile depression: meta-analysis
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Efficacy of antidepressants in juvenile depression: meta-analysis
      Available formats
      ×
Copyright
Corresponding author
Dr Evangelia M. Tsapakis, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, PO Box 80, De Crespigny Park, London SE5 8AF, UK. Email: e.tsapakis@iop.kcl.ac.uk
Footnotes
Hide All

Declaration of interest

E.M.T. has received research support from Johnson & Johnson Psychiatry Research and Development. L.T. has received research support or served as a consultant to JDS, IFI, Eli Lilly and Janssen Pharmaceutical Corporations. R.J.B. is a consultant to or has received research support from Janssen, IFI, JDS, Eli Lilly, Novartis and Solvay Pharmaceutical Corporations. Funding is detailed in the Acknowledgements.

Footnotes
References
Hide All
1 Committee on Safety of Medicines. Selective Serotonin Reuptake Inhibitor Antidepressants (http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON1004259?ssSourceNodeld=242&ssTargetNodeld=221) (accessed 16 Dec 2007).
2 Jureidini, JN, Doecke, CJ, Mansfield, PR, Haby, MM, Menkes, DB, Tonkin, AL. Efficacy and safety of antidepressants for children and adolescents. BMJ 2004; 328: 879–83.
3 Hammad, TA, Laughren, T, Racoosin, J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006; 63: 332–3.
4 Newman, TB. A black-box warning for antidepressants in children? N Engl J Med 2004; 351: 1595–8.
5 March, JS, Silva, S, Petrycki, S, Curry, J, Wells, K, Fairbanks, J, Burns, B, Domino, M, McNulty, S. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression. Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. JAMA 2004; 292: 807–20.
6 Baldessarini, RJ, Pompili, M, Tondo, L, Tsapakis, EM, Soldani, F, Faedda, GL, Hennen, J. Antidepressants and suicidal behaviour: are we hurting or helping? Clin Neuropsychiatry 2005; 2: 73–5.
7 Baldessarini, RJ, Pompili, M, Tondo, L. Suicidal risk in antidepressant trials: Commentary. Arch Gen Psychiatry 2006; 63: 332–9.
8 Mann, JJ, Emslie, G, Baldessarini, RJ, Beardslee, W, Fawcett, JA, Goodwin, FK, Leon, AC, Meltzer, HY, Ryan, ND, Shaffer, D, Wagner, KD. ACNP Task force report on SSRIs and suicidal behavior in youth. Neuropsychopharmacol 2006; 31: 473–92.
9 Hammad, TA, Laughren, T, Racoosin, L. Suicidality in paediatric patients treated with antidepressants. Arch Gen Psychiatry 2006, 63: 332–9.
10 Food and Drug Administration: Laughren TP. Overview for a Meeting of the Psychopharmacology Drug Advisory Committee (PDAC) Concerning Suicidal Risk in Trials of Antidepressant Drugs in Juvenile and Adult Patients (http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-index.htm) (accessed 16 Dec 2007).
11 Olfson, M, Marcus, SC, Shaffer, D. Antidepressant drug therapy and suicide in severely depressed children and adults. Arch Gen Psychiatry 2006; 63: 865–72.
12 Bridge, JA, Iyengar, S, Salary, CB, Barbe, RP, Birmaher, B, Pincus, HA, Ren, L, Brent, DA. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment. JAMA 2007; 287: 1683–96.
13 Friedman, RA, Leon, AC. Expanding the black box: depression, antidepressants, and the risk of suicide. N Engl J Med 2007; 356: 2343–6.
14 Libby, A, Brent, D, Morrato, E, Orton, HD, Allen, R, Valuck, RJ. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry 2007; 164: 884–91.
15 Morrato, EH, Libby, AM, Orton, HD, Degruy, FV, Brent, DA, Allen, R, Valuck, RJ. Frequency of provider contact after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psychiatry 2008; 165: 4250.
16 Valuck, RJ, Libby, AM, Orton, HD, Morrato, EH, Allen, R, Baldessarini, RJ. Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psychiatry 2007; 164: 1198–205.
17 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III); 3rd revised edn (DSM–III–R); 4th edn (DSM–IV); 4th edn text revision (DSM–IV–TR). APA Press, 1980, 1987, 1994, 2000.
18 World Health Organization. International Classification of Diseases (ICD): Classification of Mental and Behavioural Disorders, Clinical Descriptions and Diagnostic Guidelines, ninth edition (ICD–9) and tenth edition (ICD–10). WHO, 1977, 1992.
19 Kramer, AD, Feiguine, RJ. Clinical effects of amitriptyline in adolescent depression. J Am Acad Child Adolesc Psychiatry 1981; 20: 636–44.
20 Petti, TA, Law, W. Imipramine treatment of depressed children: double-blind pilot study. J Clin Psychopharmacol 1982; 2: 107–10.
21 Puig-Antich, J, Perel, JM, Lupatkin, W, Chambers, WJ, Tabrizi, MA, King, J, Goetz, R, Davies, M, Stiller, RL. Imipramine in prepubertal major depressive disorders. Arch Gen Psychiatry 1987; 44: 81–9.
22 Bernstein, GA, Garfinkel, BD, Borchardt, CM. Comparative studies of pharmacotherapy for school refusal. J Am Acad Child Adolesc Psychiatry 1990; 5: 773–81.
23 Geller, B, Cooper, TB, Graham, DL, Marsteller, FA, Bryant, DM. Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a fixed plasma level design. Psychopharmacol Bull 1990; 26: 8590.
24 Hughes, CW, Preskorn, SH, Wrona, M, Hassanein, R, Tucker, S. Follow-up of adolescents initially treated for prepubertal-onset major depressive disorder with imipramine. Psychopharmacol Bull 1990; 26: 244–8.
25 Simeon, JG, Dinicola, VF, Ferguson, HB, Copping, W. Adolescent depression: placebo controlled fluoxetine treatment study and follow-up. Prog Neuropsychopharmacol Biol Psychiatry 1990; 14: 791–5.
26 Boulos, C, Kutcher, S, Marton, P, Simeon, J, Ferguson, B, Roberts, N. Response to desipramine in adolescent major depression. Psychopharmacol Bull 1991; 27: 5965.
27 Geller, B, Cooper, TB, Graham, DL, Fetner, HH, Marsteller, FA, Wells, JM. Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6- to 12-year-olds with major depressive disorder. J Am Acad Child Adolesc Psychiatry 1992; 31: 3444.
28 Kutcher, S, Boulos, C, Ward, B, Marton, P, Simeon, J, Ferguson, HB, Szalai, J, Katic, M, Roberts, N, Dubois, C, Reed, K. Response to desipramine treatment in adolescent depression: a fixed-dose, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 1994; 33: 686–94.
29 Kye, CH, Waterman, GS, Ryan, ND, Birmaher, B, Williamson, DE, Iyengar, S, Dachille, S. A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression. J Am Acad Child Adolesc Psychiatry 1996; 35: 1139–44.
30 Emslie, GJ, Rush, AJ, Weinberg, WA, Kowatch, RA, Hughes, CW, Carmody, T, Rintelmann, J. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997; 54: 1031–7.
31 Emslie, GJ, Heiligenstein, JH, Wagner, KD, Hoog, SL, Ernest, DE, Brown, E, Nilsson, M, Jacobson, JG. Fluoxetine for acute treatment in depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry 2002; 41: 1205–15.
32 Emslie, GJ, Findling, RL, Yeung, PP, Kunz, NR, Li, Y. Venlafaxine ER for the treatment of pediatric subjects with depression: Results of two placebo-controlled trials. J Am Acad Child Adolesc Psychiatry 2007; 46: 479–88.
33 Sallee, FR, Vrindavanam, NS, Deas-Nesmith, D, Carson, SW, Sethuraman, G. Pulse intravenous clomipramine for depressed adolescents: double-blind, controlled trial. Am J Psychiatry 1997; 154: 668–73.
34 Birmaher, B, Waterman, GS, Ryan, ND, Perel, J, McNabb, J, Balach, L, Beaudry, MB, Nasr, FN, Karambelkar, J, Elterich, G, Quintana, H, Williamson, DE, Rao, U. Randomized controlled trial of amitriptyline vs. placebo for adolescents with ‘treatment-resistant’ major depression. J Am Acad Child Adolesc Psychiatry 1998; 37: 527–35.
35 Klein, RG, Mannuzza, S, Koplewicz, HS, Tancer, NK, Shah, M, Liang, V, Davies, M. Adolescent depression: controlled desipramine treatment and atypical features. Depress Anxiety 1998; 7: 1531.
36 Avci, A, Diler, RS, Kibar, M, Toros, F. Comparison of moclobemide and placebo in young adolescents with major depressive disorder. Ann Med Sciences 1999; 8: 3140.
37 Milin, R., Simeon, J., Spenst, W. Double-blind study of paroxetine in adolescents with unipolar major depression (GSK trial 29060/377). In Proceedings of the Forty-sixth Annual Meeting of the American Academy of Child and Adolescent Psychiatry, 1999 October 19–24, Chicago, Illinois, USA (http://www.gsk.com/media/paroxetine/depression_377_full.pdf) (accessed 16 Dec 2007).
38 Deas, D, Randall, CL, Roberts, JS, Anton, RF. A double-blind, placebo-controlled trial of sertraline in depressed adolescent alcoholics: a pilot study. Hum Psychopharmacol 2000; 15: 461–9.
39 Keller, MB, Ryan, ND, Strober, M, Klein, RG, Kutcher, SP, Birmaher, B, Hagino, OR, Koplewicz, H, Carlson, GA, Clarke, GN, Emslie, GJ, Feinberg, D, Geller, B, Kusumakar, V, Papatheodorou, G, Sack, WH, Sweeney, M, Wagner, KD, Weller, EB, Winters, NC, Oakes, R, McCafferty, JP. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry 2001; 40: 762–72.
40 Food and Drug Administration. Pediatric Supplement SE5-011 Executive Summary. FDA, 2001 (http://www.fda.gov/cder/foi/esum/2004/20415SE5_011_Mirtazapine%20MO%20ReviewFIN.pdf) (accessed 16 Dec 2007).
41 Rynn, MA, Findling, RL, Emslie, GJ, Marcus, RN, Fernandes, LA, D'Amico, MF, Hardy, SA. Efficacy and safety of nefazodone in adolescent with MDD (Abstract NR57). In Proceedings of the 155th Annual Meeting of the American Psychiatric Association (in Philadelphia, PA, May 18–23): New Research. American Psychiatric Press. 2002.
42 Wagner, KD, Ambrosini, P, Rynn, M, Wohlberg, C, Yang, R, Greenbaum, MS, Childress, A, Donnelly, C, Deas, D. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 2003; 290: 1033–41.
43 Wagner, KD, Robb, AS, Findling, RL, Jin, J, Gutierrez, MM, Heydorn, WE. Randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Am J Psychiatry 2004; 161: 1079–83.
44 Beecham, SmithKline. A Randomized, Multicenter, 8-Week, Double-blind, Placebo-controlled Flexible-dose Study to Evaluate the Efficacy and Safety of Paroxetine in Children and Adolescents with Major Depressive Disorder (29060/701). GSK. 2001 (www.gsk.com/media/paroxetine/depression_701_full.pdf) (accessed 16 Dec 2007).
45 Moher, D, Cook, DJ, Eastwood, S, Olkin, I, Rennie, D, Stroup, DF. Improving the quality of reports of meta-analyses of randomized controlled trials: the QUOROM statement. Lancet 1999; 354: 1896–900.
46 Baldessarini, RJ, Drug therapy of depression and anxiety disorders. In Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th edn (eds Brunton, LL, Lazo, JS, Parker, KL): 429–59. McGraw-Hill, 2005.
47 DerSimonian, R, Laird, N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–88.
48 Begg, CB, Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088–111.
49 Egger, M, Davey-Smith, G, Schneider, M, Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–34.
50 Altman, DG. Confidence intervals for the number needed to treat. BMJ 1988; 317: 1309–12.
51 Jadad, AR, Moore, RA, Carroll, D, Jenkinson, C, Reynolds, DJ, Gavaghan, DJ, McQuay, HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 112.
52 Spitzer, R, Endicott, J, Robins, E. Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders, 3rd edn. New York State Psychiatric Institute, Biometrics Research Division, 1978.
53 Fawcett, J, Barkin, RL. Efficacy issues with antidepressants. J Clin Psychiatry 1997; 58 (suppl 6): 32–9.
54 Janicak, PG, Davis, JM, Preskorn, SH, Ayd, FJ. Treatment with antidepressants. In Principles and Practice of Psychopharmacology, 3rd edn: 214325. Lippincott/Williams & Wilkins, 2001.
55 Khan, A, Detke, M, Khan, SR, Mallinckrodt, C. Placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis 2003; 191: 211–8.
56 National Institute for Clinical Excellence. Depression in Children and Young People: Identification and Management in Primary, Community and Secondary Care (CG28). NICE, 2005 (http://www.nice.org.uk/nicemedia/pdf/cg028fullguideline.pdf).
57 Hazell, P, O'Connell, D, Heathcote, D, Robertson, J, Henry, D. Efficacy of tricyclic drugs in treating child and adolescent depression: meta-analysis. BMJ 1995; 310: 897901.
58 Hazell, P, O'Connell, D, Heathcote, D, Henry, D. Tricyclic drugs for depression in children and adolescents. Cochrane Database of Systematic Reviews, issue 2. Update Software, 2002.
59 Jureidini, JN, Doecke, CJ, Mansfield, PR, Haby, MM, Menkes, DB, Tonkin, AL. Efficacy and safety of antidepressants for children and adolescents. BMJ 2004; 328: 879–83.
60 Courtney, DB. Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: systematic review of published randomized controlled trials. Can J Psychiatry 2004; 49: 557–63.
61 Whittington, CJ, Kendall, T, Fonagy, P, Cottrell, D, Cotgrove, A, Boddington, E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published vs. unpublished data. Lancet 2004; 363: 1341–5.
62 Cheung, AH, Emslie, GJ, Mayes, TL. Review of the efficacy and safety of anti-depressants in youth depression. J Child Psychol Psychiatry 2005; 46: 735–54.
63 Ryan, ND. Treatment of depression in children and adolescents. Lancet 2005; 366: 933–40.
64 Tonkin, A, Jureidini, J. Wishful thinking: antidepressant drugs in childhood depression. Br J Psychiatry 2005; 187: 304–5.
65 Raz, A. Perspectives on the efficacy of antidepressants for child and adolescent depression. PLoS Med 2006; 3: e9.
66 Baldessarini, RJ, Faedda, GL, Hennen, J. Risk of mania with serotonin reuptake inhibitors vs. tricyclic antidepressants in children, adolescents and young adults. Arch Pediatr Adolesc Med 2005; 159: 298–9.
67 Zito, JM, Safer, DJ, dosReis, S, Gardner, JF, Boles, M, Lynch, F. Trends in prescribing of psychotropic medications to preschoolers. JAMA 2000; 283: 1025–30.
68 Zito, JM, Safer, DJ, dosReis, S, Gardner, JF, Magder, L, Soeken, K, Boles, M, Lynch, F, Riddle, MA. Psychotropic practice patterns for youth. A 10-year perspective. Arch Pediatr Adolesc Med 2003; 157: 1725.
69 Delate, T, Gelenberg, AJ, Simmons, VA, Motheral, BR. Trends in the use of antidepressants in a national sample of commercially insured paediatric patients, 1998 to 2002. Psychiatr Serv 2004; 55: 387–91.
70 Birmaher, B, Ryan, ND, Williamson, DE, Brent, DA, Kaufman, J, Dahl, RE, Perel, J, Nelson, B. Childhood and adolescent depression: review of the past ten years. Part I. J Am Acad Child Adolesc Psychiatry 1996; 35: 1427–39.
71 Birmaher, B, Ryan, ND, Williamson, DE, Brent, DA, Kaufman, J. Childhood and adolescent depression: review of the past 10 years. Part II. J Am Acad Child Adolesc Psychiatry 1996; 35: 1575–83.
72 Harrington, R, Whittaker, J, Shoebridge, P, Campbell, F. Systematic review of efficacy of cognitive behavior therapies in childhood and adolescent depressive disorder. BMJ 1998; 316: 1559–63.
73 Timimi, S. Rethinking childhood depression. BMJ 2004; 329: 1394–7.
74 Biederman, J, Faraone, SV, Baldessarini, RJ, Flood, J, Meyer, M, Wilens, T, Spencer, T, Chen, L, Weber, W. Predicting desipramine levels in children and adolescents: a naturalistic clinical study. J Am Acad Child Adolesc Psychiatry 1997; 36: 384–9.
75 Wilens, TE, Cohen, L, Biederman, J, Abrams, A, Neft, D, Faird, N, Sinha, V. Fluoxetine pharmacokinetics in pediatric patients. J Clin Psychopharmacol 2002; 22: 568–75.
76 Wolraich, M, Felice, ME, Drotar, D. Classification of Child and Adolescent Mental Diagnoses in Primary Care: Diagnostic and Statistical Manual for Primary Care, Child and Adolescent Version (DSM–PC). American Academy of Paediatrics, 1996.
77 American Academy of Child and Adolescent Psychiatry. Practice parameters for assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry 1998; 37 (suppl 10): 63–83S.
78 Birmaher, B, Heydl, P. Biological studies in depressed children and adolescents. Int J Neuropsychopharmacol 2001; 4: 149–57.
79 Hrobjartsson, A, Gotzsche, PC. Is the placebo powerless? Analysis of clinical trials comparing placebo with no treatment. NEnglJ Med 2001; 344: 1594–602.
80 Kaufman, J, Martin, A, King, RA, Charney, D. Are child-, adolescent-, and adult-onset depression one and the same disorder? Biol Psychiatry 2001; 9: 9801001.
81 Martin, A, Kaufman, J, Charney, D. Pharmacotherapy of early-onset depression. Update and new directions. Child Adolesc Psychiatr Clin N Am 2000; 9: 135–57.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×
Type Description Title
PDF
Supplementary materials

Tsapakis et al. supplementary material
Supplementary Table S1-S3

 PDF (56 KB)
56 KB
PDF
Supplementary materials

Tsapakis et al. supplementary material
Supplementary Table S1-S3

 PDF (56 KB)
56 KB
PDF
Supplementary materials

Tsapakis et al. supplementary material
Supplementary Table S1-S3

 PDF (56 KB)
56 KB
UNKNOWN
Supplementary materials

Tsapakis et al. supplementary material
Supplementary Material

 Unknown (481 bytes)
481 bytes

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Efficacy of antidepressants in juvenile depression: meta-analysis

  • Evangelia M. Tsapakis (a1), Federico Soldani (a2), Leonardo Tondo (a3) and Ross J. Baldessarini (a4)
Submit a response

eLetters

Re: Antidepressants in depressed adolescents: to prescribe or not to prescribe?

Evangelia M Tsapakis, Clinical Research Fellow and Honorary Specialist Registrar in General Adult Psychiatry
20 October 2008

We agree with Menon (1) that, in clinical practice, many depressed juvenile patients almost certainly are under-diagnosed, reluctant to accept treatment, under-treated or leave treatment prematurely, and that competent clinical help, especially other than use of antidepressants, forsuch patients and their families is hard to find. However, the proposition (1) that antidepressants may have similar effects at all ages is inconsistent with our findings of quite limited, and perhaps inversely age-dependent, efficacy of antidepressants, as a class, as well as a lack of statistically significant differences between older and modern agents (especially of TCAs vs. SRIs), and the powerful influence of study-size onconclusions about “significance” of separation of antidepressants from placebos (2).

A timely and pressing question is whether antidepressant treatment alters suicidal risks. Depression and suicide are strongly associated, but prediction of suicidal behavior, even in depressed individuals, is very difficult, and evidence concerning relationships of antidepressant treatment to suicidal behavior, although consistent in randomised clinical trials, remains controversial (3,4). Whether or not youth suicide rates will consistentlyincrease or decrease, remains to be seen, and to be sorted out from high internationalvariation in yearly suicide rates and poor documentation of attempts (3).

For now, it seems an inescapable conclusion that clinicians are left to their own clinical judgment about using antidepressants for young individuals diagnosed with major depressive disorder. Furthermore, disbelief that modern antidepressants show relatively modest effects compared to placebos, and failed to separate statistically from older agents (2), paired with the repeated, and the poorly documented assertion that some modern antidepressants work well in clinical practice seems to avoid the issues. We considered various ways in which even randomized, controlled trials may be misleading, including selection of atypical or mildly ill outpatients or use of inadequate doses of antidepressants (2), as well as current controversy about how to diagnose and quantify changes in affective disorders in children and adolescents (5). Nevertheless, it is difficult to simply dismiss and ignore the findings of the research that has been done to test the efficacy of antidepressants in juvenile depression (2).

References

1Menon, K. Antidepressants in depressed adolescents: to prescribe ornot to prescribe? Br J Psychiatry 2008 [e-publ 21 August].

2Tsapakis EM, Soldani F, Tondo L, Baldessarini RJ. Efficacy of antidepressants in juvenile depression: meta-analysis. Br J Psychiatry 2008; 193: 10–7.

3Baldessarini RJ, Tondo L, Strombom I, Dominguez S, Fawcett J, Oquendo M, Licinio J, Valuck R, Tollefson G, Tohen M: Analysis of ecological studies of relationships between antidepressant utilization andsuicidal risk. Harv Rev Psychiatry 2007: 15: 133–45.

4Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006; 63: 332–3.

5Henry C, Demotes-Mainard J. SSRIs, suicide and violent behavior: isthere a need for a better definition of the depressive state? Curr Drug Saf 2006; 1: 59–62.
... More

Conflict of interest: None Declared

Write a reply

Antidepressants in depressed adolescents: to prescribe or not to prescribe?

Krishna Menon, Specialty Doctor
21 August 2008

I read with great interest the results of the meta analysis on the efficacy of antidepressants in juvenile depression published in the July,2008 of the British Journal of Psychiatry. Despite the possible heterogeneity among some of the studies included in the study, the results, if accepted by the psychiatric fraternity, could lead to further reduction in the use of antidepressants in the child & adolescent population. The use of antidepressants in this group has already decreasedby 33% since the CSM warning against the use of most antidepressants in children & adolescents (1). Although the NICE guidelines on the treatment of depression among children and adolescents states that medication should only be used in conjunction with psychological interventions, the provision of psychological therapies remain thin on theground in most parts of the country, which means that medication is often the only option available to clinicians for treatment of severe depression.

Although purely pharmacological treatment would be the least desirable option in depression and research evidence on the efficacy for antidepressants for depressants in all age groups is either mixed or at best shaky, depending on which side of the debate one is on (2), most clinicians would agree that many patients with significant depression do improve on antidepressants. Although it is too early to judge whether reduction in antidepressant prescribing resulting from the CSM warning hasresulted in an increase in depressive morbidity among children & adolescents in the UK, disturbing evidence is already emerging from the United States, Canada and the Netherlands (3) on an increase in completed suicide among children and adolescents, which seems to coincide with the reduction in antidepressant prescribing following warnings by regulatory agencies. In a retrospective study done in Canada, a significant reductionin antidepressant prescribing, accompanied by a statistically significant increase in suicide among children and adolescents (RR 1.25, 95% CI 1.08–1.44; annual rate per 1000 = 0.04 before and 0.15 after the warning) was noted in the 2 years following issuance of the warning(4)

Given the well established link between depression and suicide, one can only conclude that clinicians may be under treating depression in children and adolescents since the emergence of concerns in relation to antidepressants. I feel clinicians should use their own clinical judgementand take into account local resources before making decisions on the course of treatment in juvenile depression. This would help one maintain the right balance between evidence based practice and what's best for individual patients, especially in an area of practice were research evidence is often ambiguous and contradictory.

References:

1)Benji T Kurian, Wayne A Ray, Patrick D Arbogast et al Effect of regulatory warnings on antidepressant prescribing in children & adolescents. Arch Pedia Adolsec Medicine Vol 161 (No 7) July 2007

2)Joanna Moncrieff,Irving Kirsch Efficacy of antidepressants in adults. BMJ 2005;331:155-157 (16 July), doi:10.1136/bmj.331.7509.155

3)http://pn.psychiatryonline.org/cgi/content/full/43/10/14

4)Laurence Y. Katz, Anita L. Kozyrskyj, Heather J. Prior et al Effectof regulatory warnings on antidepressant prescription rates, use of healthservices and outcomes among children, adolescents and young adults. Can Med Assc Journal April 8, 2008; 178 (8). doi:10.1503/cmaj.071265
... More

Conflict of interest: None Declared

Write a reply

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *