Treatment of major depressive disorder in children and adolescents: Most selective

serotonin reuptake inhibitors are no longer recommended

Author(s): Paul Ramchandani
Source: BMJ: British Medical Journal, Vol. 328, No. 7430 (3 January 2004), pp. 3-4
Published by: BMJ
Stable URL: http://www.jstor.org/stable/41708248
Accessed: 05-12-2017 02:02 UTC

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 Editorials

We are grateful for the assistance of Peter Suber and Jan

contrast, a model where publishers charge for value
added by others (the researchers) will be found out-Velterop
as in compiling the contents of the box.

Reed Elsevier is beginning to discover. Indeed, it could

TD is a member of the national advisory committee of PubMed
even be argued that some publishers subtract rather
Central and a signatory of the Bethesda Statement on Open
than add value- because the minimal value they add is
Access Publishing. TD and RS are employed by the BMJ
more than undone by their Balkanising medical
Publishing Group, which depends on the traditional subscrip-
tion model for a substantial proportion of its revenue.
research, making systematic reviews, for example, diffi-
cult and expensive.
All change is resisted. Three things seem necessary
1 Turner N. PLOS Biology. BMJ 2004;328:56.
for resistance to be overcome and change to happen: a PO, Eisen MB, Varmus HE. Why PloS became a publisher. PLoS
2 Brown
'burning platform," a vision of something better, and Biol 2003 October;l(l):e36 D01:10.1371/journal.pbio.0000036
"next steps." The burning platform has been present3 for
Delamothe T, Godlee F, Smith R. Scientific literature's open sesame? BMJ
2003;326;945-6.
a long time among librarians but now has spread to 4aca-
Goldsmith C, Larsen K. Reed Elsevier's net jumped on solid subscription
demics, particularly in the United States. The vision ofsales. Whll Street Journal Online 21 February 2003 (accessed 22 Dec 2003).
5 Gooden P, Owen M, Simon S, Singlehurst L. Scientific publishing: knowledge
something better arrived with the internet The "next is power, www.econ.ucsb.edu/ ~ tedb/Journals/morganstanley.pdf (accessed
step" is now provided by the idea of authors paying. The 19 Dec 2003).
result, we predict, will be the rapid achievement of6 the
Economic analysis of scientific research publishing: a report commissioned
by the WeUcome Trust. London: Wellcome, 2003. www.wellcome.ac.uk/
dream of open access to scientific research. scipublishing (accessed 22 Dec 2003).
7 Velterop J. Public funding, public knowledge, publication. Serials
Tony Delamothe web editor bmj.com 2003;16:169-74. www.uksg.org/serials.asp (accessed 22 Dec 2003).
Richard Smith editor BMJ 8 Buder D. Who will pay for open access? Nature 2003;425:554-5.

Treatment of major depressive disorder in children

and adolescents
Most selective serotonin reuptake inhibitors are no longer recommended

1 in 10. It is also the only drug labelled for use in mzgor

chairman of the Committee on Safety of depressive disorder in children in the United States.
On Medicines chairmanMedicines10 December of in the
in the United the 2003
Kingdom, advisedUnited Committee Professor Kingdom, Gordon on Safety advised Duff, of The new advice raises several questions, two of
that most of the antidepressant drugs in the selective which are addressed here. Firstly, how should we treat
serotonin reuptake inhibitor group should not be used depressive disorder in children and adolescents now?
to treat major depressive disorder in children and ado- Secondly, are there lessons to be learnt from the way in
lescents under the age of 18 years.1 This is the main cat- which these events have unfolded?
egory of medication used in the treatment of Depressive disorder is a common and debilitating
depression in children and adolescents, and the condition. It costs approximately 9bn ($16bn; 13bn)
announcement will have taken many young people in England each year,3 and worldwide is the fourth
who take these drugs, their parents, and doctors by sur- most important cause of disability.4 Key symptoms are
prise. Although the advice only applies to the United low mood, loss of energy, and loss of enjoyment Many
Kingdom, it mirrors concerns that are also being other symptoms can occur including suicidal thoughts.
considered by the US Food and Drug Administration.2 It becomes increasingly common through adoles-
The new advice follows the review of data from cence.5 In recent years the number of prescriptions for
clinical trials by an expert working group, convened antidepressant medication in this age group has
initially because of concerns that selective serotonin
grown, although the use of these drugs is beyond the
reuptake inhibitors may increase the risk of suicidalscope of the product licence. About half of the
thoughts and self harm in young people. The group estimated 40 000 young people under the age of 18
concluded that the balance of risks and benefits was years using antidepressants in the United Kingdom are
unfavourable for three of the selective serotonin currently taking one of the newly "contraindicated"
reuptake inhibitors (sertraline, Citalopram, andantidepressant
escita- medications.1
lopram) and that there was insufficient evidence Fortothose children and adolescents currently taking
support the use of a fourth, fluvoxamine. oneThe
of these antidepressants for depressive disorder,
committee had earlier advised that two other the most important advice is that they should not sud-
antidepressants (paroxetine and venlafaxine) denlyshould
stop taking their medication. This may result in
not be used to treat depression in this age group. Some
withdrawal effects and will increase the risk of relapse
of the data on which this decision was based had not of depression. Seeking medical advice is crucial- it may
previously been released to the committee. be that the current medication is continued or that it is
Fluoxetine is now the only selective serotonin gradually withdrawn or replaced.
reuptake inhibitor for which the committee considers For those children and adolescents newly present-
the balance of risks and benefits to be favourable, ing with depression the situation is different
Symptoms of depression are common, particularly in
although it cautions that the drug is likely to be benefi-
BMJ 2004;328:3-4 adolescence,
cial in only a minority of patients- the figure quoted is and often resolve without psychological

BMJ VOLUME 328 3 JANUARY 2004 bmj.com 3

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Editorials

or medical intervention. The diagnosis of depressivefluoxetine10"12 seems marginal on the basis of the avail-
disorder requires careful assessment If treatment isable evidence. Independently funded research into the
indicated several options remain. Psychological treat- effectiveness of treatments for depression is needed.
ments, including cognitive behaviour therapy, have Concerns also remain about the way in which data
been used extensively, and several randomised trialsfrom trials about serious adverse effects of some
attest to its efficacy in mild or moderately severeantidepressant drugs, held by the pharmaceutical
depression.6 Where available, psychological treatmentscompanies concerned, seem not to have been
previously released to the Committee on Safety of
are often used as a first line treatment, particularly in
younger adolescents and children. However, little Medicines. A more robust system, requiring full disclo-
evidence exists to support their use in young peoplesure of information, is urgently required.
with more severe depression, and here pharmacologi- Paul Ramchandani MRC fellow
cal treatments may be important Section of Child and Adolescent Psychiatry, University of Oxford
Fluoxetine remains an option, and it is probably Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX
(paul.ramchandani@psych.ox.ac.uk)
now being used as the first line pharmacological treat-
ment in most patients. It can have problematic adverse holds a special training fellowship in health services research
PR
funded by the UK Medical Research Council and is an honorary
effects, including restlessness and agitation. The otherconsultant child and adolescent psychiatrist
selective serotonin reuptake inhibitors may still be used
Competing interests: None declared.
in some circumstances under specialist supervision.
The other main category of antidepressant drugs is1 Committee on Safety of Medicines. Use of selective serotonin reuptake
inhibitors (SSRIs) in children and adolescents with major depressive dis-
the tricyclic drugs. Their use has declined since the order (MDD). www.mhra.gov.uk/ (accessed 16 Dec 03).
introduction of the selective serotonin reuptake inhibi-2 Food and Drug Administration. Reports of suicidality in pediatric
patients being treated with antidepressant medications for major depres-
tors and particularly since a systematic review in 1995 sive disorder (MDD). FDA Talk Paper T03-70 (27 October 2003)
concluded that they seem to be no more effective than (www.fda.gov/bbs/topics/AN SWERS/2003/ANS0 1 256.html) (accessed
12 Dec 03).
placebo in the treatment of depression in children and 3 Thomas CM, Morris S. Cost of depression among adults in England in
adolescents.7 A more recent Cochrane systematic review 2000. Br J Psychiatry 2003;183:514-9.
4 Murray CJ, Lopez AD. Regional patterns of disability-free life expectancy
showed that they may offer some benefit for adolescents and disability-adjusted life expectancy: global burden of disease study.
with depression but not for pre-pubertal children.8 Lancet 1997;349:1347-52.
5 Meitzer H, Gatward R, Goodman R, Ford T. Mental health of children and
These drugs are associated with clinically important adolescents in Great Britain. London: Stationery Office, 2000.
adverse effects, and most are toxic in overdose. 6 Harrington R, Whittaker J, Shoebridge P, Campbell F. Systematic review
of efficacy of cognitive behaviour therapies in childhood and adolescent
What are the lessons to be learnt from the way in
depressive disorder. BMJ 1998;316:1559-63.
which these events have unfolded? The dramatic 7 Hazell P, O'Connell D, Heathcote D, Robertson J, Henry D. Efficacy of tri-
cyclic drugs in treating child and adolescent depression: a meta-analysis.
issuing of the guidance by the Committee on Safety of
BMJ 1995;310:897-901.
Medicines is likely to lead to considerable uncertainty
8 Hazell P, O'Connell D, Heathcote D, Henry D. Tricyclic drugs for depres-
and some difficulty for many patients and doctors. sion in children and adolescents. Cochrane Database Syst Rev
2003;(4):CD0023 1 7.
Although the guidance is clear cut, the decisions
9 WagnerhaveKD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MD,
been based on relatively few studies. The dearth of of sertraline in the treatment of children and adolescents
et al. Efficacy
with major depressive disorder; two randomised controlled trials. JAMA
research means that a high proportion of the 40 000
2003;290:1033-41.
children and adolescents taking antidepressants 10 Simeon
in the JG, Dinicola VF, Ferguson HB, Copping W. Adolescent
depression: a placebo-controlled fluoxetine study and follow-up. Prog
United Kingdom are likely to use fluoxetine in the
Neuropsychopharmacol Biol Psychiatry 1990;14:791-5.
future on the basis of randomised trials involving a few
1 1 Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody
T, et al. A double-blind, placebo-controlled trial of fluoxetine in children
hundred people, the largest of which was funded by the
and adolescents with depression. Arch Gen Psychiatry 1997;54:1031-7.
company that makes the drug. The difference in effec-
12 Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E,
et al. Fluoxetine for acute treatment of depression in children and
tiveness between sertraline (subject of the new adolescents;
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from the Committee on Safety of Medicines9)Child andAdolesc Psychiatry 2002 ;4 1 : 1 205- 1 5.

Choice and responsiveness for older people in the

"patient centred" NHS
New community care regulations mean that older people may not be able to choose
where they are treated

From January 2004 local authorities will be fined

patient centred NHS driven by the principles by the NHS for failing to arrange social care services
According h. patienth. ofofchoice
choiceandcentred to the and
competition will health
improveNHS competition driven secretary, by the will John principles improve Reid, a for patients who are no longer appropriately situated
equitable access to health care in particular for the in an acute hospital bed. Under the provisions of the
poor and disadvantaged. The patient, and not the pro- Community Care Act social service departments will
vider, will be king while NHS provision will still be pro- have a minimum of two days to assess the needs of a
vided on the basis of equal treatment for equal need. patient and arrange a suitable package of care-
But it is difficult to reconcile this vision of choice and whether this be at home or in other forms of
accommodation- or face a fine of 100 ($177; 142)
equity with the Community Care (Delayed Discharge)
Act, which comes into force in January 2004. for every day the patient remains in hospital. If on
BMJ 2004;328:4-5

4 BMJ VOLUME 328 3 JANUARY 2004 bmj.com

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