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Evidence Summary: Using SSRI Antidepressants and Other
Newer Antidepressants to Treat Depression in Young People: What are the issues and what is the evidence? headspace is funded by the Australian Government under the
Promoting Better Mental Health – Youth Mental Health Initiative
Section A:
Evidence Summary:
Using SSRI Antidepressants and Other Newer Antidepressants to Treat Depression in Young People: What are the issues and what is the evidence? Why is there so much debate on this issue?
severe depression (not mild depression) when psychological therapy has not been effective, is not available or is refused Concerns about using Selective Serotonin Reuptake or if symptoms are severe (16). The guidelines state that Inhibitors (SSRIs) in young people centre on two issues. First, prescription must occur in the context of an ongoing SSRIs might be less effective than first thought for treating therapeutic relationship and management plan. adolescent depression. Second, SSRIs might be associated Guidelines also recommend close monitoring of symptom with worrying side-effects. The latter concern first emerged severity and adverse effects, including the onset or increase in in light of evidence indicating an increase in suicidal ideas suicidal thinking especially in the first 4 weeks of commencing and behaviours among people aged 12-18 years who were medication, and that there be a protocol in place for prescribed SSRIs for the treatment of depressive illnesses (1-4). This led to a ‘black box warning’ in the United States cautioning clinicians about using this class of medication for young people aged up to 24 years. In Australia, no Are SSRIs and Newer Antidepressants
antidepressant (including any SSRIs) is currently approved by effective for young people? What is
the Therapeutic Goods Administration (TGA) for the treatment the evidence?
of major depression in people aged less than 18 years (5). As a result of the warnings and associated publicity, SSRI Additional evidence is available since the publication of prescription rates were observed to decline among young the Australian guidelines in 2011. The results of a recently people in many countries (6). However, an association published Cochrane systematic review (15) show modest has recently been drawn between these declining rates of effects of antidepressants compared with placebo in prescriptions and an increased suicide rate over the same improving depression. The rates of remission while on an period of time (6). One study has shown that there has been antidepressant were 448 per 1000 compared to 380 per 1000 no increase in psychotherapy referrals to compensate for the decreasing prescription rates (7), suggesting that there has Despite the evidence supporting fluoxetine (and more recently been a reduction in interventions generally for young people escitalopram has received FDA approval), the Cochrane with depression, rather than SSRI prescriptions specifically. review showed the effects for these medications were similar There continues to be strong debate on this topic, to others included in the review2. The overall reduction in with many clinical researchers arguing that SSRIs are depression severity scores on the Children’s Depression Rating essential for treating depression in this age group, Scale-Revised (CDRS-R) was 5.63 lower for fluoxetine and 2.67 (8-12) while others claim the contrary (13-14). What further for esciptalopram compared with those on placebo (from a complicates this issue is the potential for bias to be introduced possible range of 17-113) and unlikely to indicate significant into this debate if only positive findings from SSRI drug trials clinical change for the majority of young people. For fluoxetine, are published in peer-reviewed journals, which was certainly the number needed to treat for an additional beneficial outcome (NNTB)3 of remission is 6. Rates of remission were not significantly improved on escitalopram compared with placebo. Across all SSRIs, the NNTB4 is 15.
What are evidence based guideline
recommendations for the use of medication? What kinds of patients were included in the

Current international clinical practice guidelines highlight trials that were included in the review?
fluoxetine as the only SSRI with approval from the USA Food and Drug Administration (FDA) (17,18). The FDA has also It is important to note that the majority of clinical trials have recently approved escitalopram. In Australia, guidelines excluded young people with more severe forms of depression, published in 2011 by beyondblue and the National Health including those with comorbid mental health disorders and Medical Research Council indicate that fluoxetine should (including substance use disorders) and those with suicidal only be considered for young people with moderate to ideation or deliberate self-harm. The extent to which SSRIs 1. Rates of remission are based on the median remission rate in the placebo groups post intervention.
2. Newly available data for duloxetine on the www.clinicaltrials.gov website were not available at the time of the Cochrane update.
3. NNTB is based on an assumed control risk for a group of moderately depressed young people (based on the median remission rate in the placebo group).
4. Overall NNTB calculated in the same manner as point 3 above.
Evidence Summary: Using SSRI Antidepressants and Other Newer Antidepressants
are effective for treating depression in these patients, who Overall, a stepped model approach is recommended commonly present in specialist clinical settings, is unknown. for the treatment of depression in young people (17,18), There is very little research evidence to guide practice for this whereby clinicians consider commencing treatment with a psychological therapy, such as CBT or IPT. This is especially the case for young people with mild depression. In cases of What is the evidence regarding the risks
moderate to severe depression, SSRI medication might be of using SSRIs?
considered within the context of comprehensive management of the patient, which includes regular careful monitoring for The results of several systematic reviews (4,10,15) the emergence of suicidal ideation or behaviour (17). demonstrate that there is an increased risk of both suicidal ideation and suicidal behaviour for young people treated with Irrespective of the treatment chosen, it is essential that there an SSRI compared with those receiving placebo. Across all is close monitoring of the young person’s symptoms, and any SSRIs, the risk of a suicide related outcome for those taking side effects if medication is prescribed. This also helps to form antidepressants was 58% higher (risk ratio 1.58, 95% CI 1.02 to the basis of ongoing collaborative discussions with the young 2.45), compared with those taking placebo. This equates to an person and their families and supporters where appropriate, increased risk in a group with a median baseline risk from about further treatment options for those who do not respond 25 in 1000 to 40 in 1000 (15). For fluoxetine, the number to initial treatment (including the use of increasingly complex needed to treat for an additional harmful outcome (NNTH)5 of suicidal ideation/behaviour is 32. Across all SSRIs, the NNTH6 is 66. No deaths have been reported that are Keeping up with new findings?
There are a number of sources of up-to-date What does all this mean about treating a
information about the effectiveness of interventions for young person with depression?
treating depression. The Centre of Excellence in Youth Mental Health will continue to update information about There is evidence that fluoxetine is modestly effective for effective interventions for youth mental health disorders reducing symptoms of depression in young people. Balanced www.headspace.org.au/what-works
against these findings are the even greater risks of not For more information, the beyondblue Clinical Practice treating depression, be it pharmacological or psychological. Guidelines: Depression in Adolescents and Young Adults There is a clear imperative to engage young people who are experiencing a depressive disorder in good clinical www.beyondblue.org.au/index.aspx?link_id=6.1247
care. Clinicians can consider a range of evidence-based interventions, including those that are relatively simple. For Other useful sites include:
example in the recent ADAPT trial, which compared fluoxetine with fluoxetine plus cognitive behaviour therapy (CBT), 21% The Cochrane Library - Australian Access of young people accepted into the trial responded to a www.cochrane.org.au
brief psychosocial intervention and subsequently had to be excluded from the study before randomisation (19). Trials such The Centre for Evidence Based Mental Health as ADAPT demonstrate that a high level of ‘standard care’, cebmh.warne.ox.ac.uk/cebmh/cebmh.htm
which might or might not include medication, is sufficient for The York Centre for Review and Dissemination many young people, including those experiencing moderate www.york.ac.uk/inst/crd
to severe depression (19-21). There is also evidence that psychological therapies, such as CBT and interpersonal For more general information about principles and practice therapy (IPT) can be effective for some young people, of evidence based medicine go to: The Centre for Evidence Based Medicine in Oxford www.cebm.net.
5. NNTH is based on an assumed control risk for a group of young people with moderate severity of suicidal ideation/behavior (based on the median rate in the 6. Overall NNTH calculated in the same manner as point 5 above.
Evidence Summary: Using SSRI Antidepressants and Other Newer Antidepressants
Section A:
* This evidence summary replaces the previous “Evidence Summary: Using SSRI Antidepressants to Treat Depression in Young People: What are the Issues and What is the Evidence?”. It contains updated content and trial data, and is current as of December 2012.
References
1. Hetrick, S. E., McKenzie, J. E., & Merry, S. N. (2010). The use of SSRIs 13. Moncrieff, J., & Kirsch, I. (2005). Efficacy of antidepressants in in children and adolescents. Current Opinion in Psychiatry, 23, adults. British Medical Journal, 331, 155-159.
14. Jureidini, J. N., Doecke, C. J., Mansfield, P. R., Haby, M. M., 2. Goodyer, I. M., Wilkinson, P., Dubicka, B., & Kelvin, R. (2010). Forum: Menkes, D. B., & Tonkin, A. L. (2004). Efficacy and safety of The use of selective serotonin reuptake inhibitors in depressed antidepressants for children and adolescents. British Medical children and adolescents: commentary on the meta-analysis of Hetrick et al. Current Opinion in Psychiatry, 23(58-61).
15. Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN. Newer 3. Hebebrand, J., March, J., & Herpertz-Dahlmann, B. (2010). generation antidepressants for depressive disorders in children Commentary on ;Forum: use of antidepressants in children and and adolescents. Cochrane Database of Systematic Reviews 2012, adolescents’. Current Opinion in Psychiatry, 23(62-67).
Issue 11. Art. No.: CD004851. DOI: 10.1002/14651858.CD004851.
4. Hammad, T. A., Laugren, T., & Racoosin, J. (2006). Suicidality in pediatric patients treated with antidepressant drugs. Archives of 16. McDermott, B., Baigent, M., Chanen, A., Fraser, L., Graetz, B., Hayman, N., et al. (2011). beyondblue Expert Working Committee 5. Australian Adverse Drug Reactions Advisory Committee. Use (2010) Clinical practice guidelines: Depression in adolescents of SSRI antidepressants in children and adolescents. Updated and young adults. Melbourne: beyondblue: the national statement 15 October 2004. http://www.tga.gov.au/adr/adrac_ssri.
17. American Academy of Child and Adolescent Psychiatry. (2007). 6. Gibbons, R. D., Brown, C. H., Hur, K., Marcus, S. M., Bhaumik, Practice parameter for the assessment and treatment of children D. K., Erkens, J. A., et al. (2007). Early evidence on the effects of and adolescents with depressive disorders. Journal of the regulators’ suicidality warnings on SSRI prescriptions and suicide in American Academy of Child Adolescent Psychiatry, 46, 1503–1526.
children and adolescents. American Journal of Psychiatry, 164(9), 18. National Institute for Clinical Excellence (2005). Depression in Children and Young People: Identification and management in 7. Libby, A. M., Brent, D. A., Morrato, E. H., Orton, H. D., Allen, R., & primary, community and secondary care. Leicester, UK: The British Valuck, R. J. (2007). Decline in Treatment of Pediatric Depression After FDA Advisory on Risk of Suicidality With SSRIs. American 19. Goodyer, I., Dubicka, B., Wilkinson, P., Kelvin, R., Roberts, C., Byford, Journal of Human Genetics, 164(6), 884-891.
S., et al. (2007). Selective serotonin reuptake inhibitors (SSRIs) and 8. Brent, D. A. (2004). Antidepressants and pediatric depression – the routine specialist care with and without cognitive behavior therapy risk of doing nothing. New England Journal of Medicine, 351(16), in adolescents with major depression: randomized controlled trial. British Journal of Psychiatry, 335(7611), 142 Epub.
9. Cheung, A. H., Emslie, G. J., & Mayes, T. (2005). Review of the 20. Clarke, G., Debar, L., Lynch, F., Powell, J., Gale, J., O’Connor, E., efficacy and safety of antidepressants in youth depression. Journal et al. (2005). A randomized effectiveness trial of brief cognitive of Child Psychology and Psychiatry, 46(7), 735-754.
behavioral therapy for depressed adolescents receiving antidepressant medication. Journal of the American Academy of 10. Dubicka, B., Hadley, S., & Roberts, C. (2006). Suicidal behavior Child and Adolescent Psychiatry, 44(9), 888-898.
in youths with depression treated with new-generation antidepressants: meta-analysis. Br J Psychiatry, 189, 393-398.
21. TADS Team. (2007). The Treatment for Adolescents with Depression Study (TADS): Long-term effectiveness and safety outcomes. 11. Wagner, K. D. (2005). Pharmacotherapy for major depression in Archives of General Psychiatry, 64(10), 1132-1144. children and adolescents. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29, 819-826.
22. Watanabe, N., Hunot, V., Omori, I. M., Churchill, R., & Furukawa, T. A. (2007). Psychotherapy for depression among children and 12. Whittington, C. J., Kendall, T., Fonagy, P., Cottrell, D., Cotgrove, A., adolescents: a systematic review. Acta Psychiatrica Scandinavica, & Boddington, E. (2004). Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet, 363(9418), 1341-1345.
Acknowledgements
headspace (The National Youth Mental Health Foundation) is
headspace Evidence Summaries are prepared by the Centre of
funded by the Australian Government Department of Health Excellence in Youth Mental Health. The series aims to highlight for and Ageing under the Promoting Better Mental Health – Youth service providers the research evidence and best practices for the care of young people with mental health and substance abuse problems. The content is based on the best available evidence that has been For more details about headspace visit www.headspace.org.au
Copyright 2013 Orygen Youth Health Research Centre This work is copyrighted. Apart from any use permitted under the Copyright Act 1968, no part may be reproduced without prior written permission from Orygen Youth Health Research Centre. ISBN: 978-0-9872901-8-2 (Online): 978-0-9872901-9-9 Clinical consultants:Dr Christopher Davey National Office
p +61 3 9027 0100 f +61 3 9027 0199
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Evidence Summary: Using SSRI Antidepressants and Other Newer Antidepressants

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