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
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
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
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
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’,
which might or might not include medication, is sufficient for
The York Centre for Review and Dissemination
many young people, including those experiencing moderate
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
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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
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Clinical consultants:Dr Christopher Davey
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