Should children take antidepressants?
(This article was first printed in the December
2003 issue of the Harvard Mental Health Letter.
For more information or to order, please go
[2005 Note: Lately, highly publicized concerns
about the risk of suicide have led practitioners
to exercise particular caution. To read more,
go to the FDA information on antidepressant use in children, adolescents,
Concerns about the increasing use of antidepressant
drugs by children came into focus in 2003 when
health officials in the United States, Britain,
France, and Canada issued warnings that the popular
selective serotonin reuptake inhibitor (SSRI)
paroxetine (Paxil) might increase the risk of
hostility, mood swings, aggression, and suicide
in children and adolescents. The European and
FDA warnings were based on three clinical trials
involving patients under 18 with major depression,
in which 1%–2% of those taking a placebo
and 2%–3.5% of those taking paroxetine
showed potentially suicidal behavior. There were
no suicides in either group.
Soon afterward, the manufacturer of another
popular antidepressant, venlafaxine (Effexor),
issued a similar warning based on a study in
which 2% of children and adolescents taking the
drug reported thoughts of suicide, compared with
none receiving a placebo.
How serious is the risk, and are antidepressants
worth it? These drugs probably can be useful
for children, although the evidence is mixed
and conflicting. Several controlled trials favor
antidepressants, including paroxetine and fluoxetine
(Prozac), over a placebo. A 2003 study published
in the Journal of the American Medical Association compared
sertraline (Zoloft) with a placebo in children
ages 6–17 with major depression. In two
trials, the combined response rate was 69% for
sertraline and 59% for the placebo — a
modest but statistically significant effect.
But other studies have found no benefit from
paroxetine or sertraline. Fluoxetine is the only
drug now specifically approved for major depression
in children and adolescents, but any antidepressant
approved for adult patients can legally be prescribed
Small but significant numbers of children are
actually taking the drugs. For example, a study
based on data from 1998–99 found that 5%
of 200,000 children served by Medicaid in Connecticut
received at least one psychotropic medication.
Stimulants for attention deficit disorder were
the most commonly prescribed drugs, but one quarter
of children who received any psychoactive drug
received an antidepressant.
Rarely, antidepressants are given even to children
under five. Two-year records of prescriptions
for preschool children in Oregon indicated that
about 2% had diagnosed emotional or behavior
problems. Of those, 10% were taking psychotropic
medications and 1/8 of that 10% were taking antidepressants — about
one child in 5,000. Most of these children were
not simply depressed but had severe attention
deficit disorder, post-traumatic symptoms, or
developmental disorders including autism.
The number of American children taking antidepressants
may seem low, but it is much higher than in Europe,
and it is growing. A 2003 study of nearly one
million patients under 18 enrolled in two Medicaid
systems and a health maintenance organization
found that the number of prescriptions for antidepressants
increased between 1987 and 1996 — nearly
4 times in one organization, 6 times in the second,
and 10 times in the third. Patients under 18
now account for about 5% of antidepressant prescriptions.
The public is becoming concerned about possible
overmedication. Critics fear that physicians
are adopting chemical solutions to the emotional
problems of children because of pressure from
insurers and health maintenance organizations.
Under a federal law passed in 1997, pharmaceutical
companies owning the patent for a medicine can
win an extra six months of exclusive marketing
rights by testing its efficacy in children. The
law is beginning to have its intended effects;
that’s how the findings on venlafaxine
came to light. But there is little incentive
to do such research on drugs that are not patented.
And the FDA cannot require manufacturers of a
new drug to study its effects in children before
Most psychiatric drugs have not been adequately
tested in children, and some drug combinations
occasionally prescribed for children — particularly
stimulants and antidepressants — have not
been fully tested even in adults. We don’t
know enough about either the risks or the benefits
of these medications to say whether they are
being overused or underused.
Children’s bodies do not absorb and eliminate
drugs in the same way adult bodies do, and their
brains may be affected differently as well. A
child’s development could be detoured by
a misapplication of drugs. But depression and
other conditions for which the drugs are prescribed
may also have long-lasting deleterious effects
on psychological and social development and even
on brain structure and function. Both the risks
of medicating and the risks of not medicating
are likely to be greatest in the earliest years
Children’s adverse reactions are inadequately
monitored in everyday practice. Researchers who
study side effects in children sometimes ask
the wrong questions, or not enough questions.
The FDA has a voluntary program in which physicians
report severe and novel side effects. But the
more predictable and apparently milder side effects
may also be important, especially in the long
run — which is not illuminated by clinical
trials that rarely last more than a few months.
The American Academy of Child and Adolescent
Psychiatry has established a Pediatric Psychopharmacology
Initiative. A group of educators, child psychiatrists,
developmental psychologists, and pharmaceutical
company representatives will monitor controlled
trials, set consistent standards, and promulgate
guidelines for researchers and prescribing physicians.
They will work with the National Institute of
Mental Health to publish a review of these issues
and an ethical guide for investigators.
Meanwhile, the rule is caution in prescribing
antidepressants for children. They should be
neither a first choice nor a last resort. Experts
recommend close monitoring during the first few
weeks, when SSRIs in particular may cause akathisia,
a kind of irresistible agitation that may raise
the risk of violence and self-injury (see Harvard
Mental Health Letter, October and November
2000). For children with both attention deficit
disorder and depression, experts recommend trying
a stimulant first, because its effects can be
observed immediately. If depression persists
after that, either psychotherapy or an antidepressant
may be effective.
As for paroxetine, the FDA stresses that children
and adolescents who are taking it now should
not stop abruptly, because they may suffer a
discontinuation syndrome that includes dizziness,
nausea, tremors, and anxiety. Children can continue
to take the drug if it seems to be helping, but
they should be watched closely for side effects.
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