As 2004 gets underway, antidepressant medications are on the
pharmacologic equivalent of orange alert. Safety concerns raised anew in
mid-2003 shadow the skyrocketing use of selective serotonin reuptake
inhibitors in children and adolescents.
Last June, the Food and Drug Administration advised U.S. physicians
that America’s most prescribed antidepressant, the SSRI Paxil,
should not be used in children and adolescents under age 18 due to a
possible increased risk of suicidal thoughts and attempts. The agency
recommendation followed close on the heels of a similar action in
Britain.
By late October, however, the FDA, had, in its own words,
“backed off a little bit.” It issued a public health advisory
stating that the agency had grown “increasingly skeptical”
that there was any link between antidepressant use and the risk of
suicide in children and teenagers.
The danger may be officially downgraded in February, when the
agency is set to hold a public discussion with outside experts who are
reviewing data from controlled studies of SSRIs in children and case
reports of suicide attempts. A preliminary review of 20
placebo-controlled trials of the drugs in over 4,000 children found no
completed suicides, although case reports of suicide attempts have
appeared in medical journals and the press. The FDA finds such reports
“difficult to interpret in the absence of a control group, as these
events also occur in untreated patients with depression.”
Specialists around the country believe that in contrast to a ban
imposed by British regulators, the FDA is already charting a nuanced
approach to medication availability, one that grapples with the difficult
realities of depression and its treatment at a stage in life when
impulsive behavior is at its height.
Suicide is the eleventh leading cause of death for all Americans.
It is the third leading cause of death for those aged 15 to 24.
“And the number one cause of suicide in young adults is untreated
depression,” emphasizes John Greden, M.D., chairman of psychiatry
at the University of Michigan and head of its depression center, the
nation’s first. According to the National Institute of Mental
Health, depression affects up to 2.5% of children and about 8% of
adolescents in the U.S.
In the year ending September 2003, some $10.6 billion worth of
prescriptions were written for the SSRI antidepressants. An unknown but
growing number of those were for youngsters between the ages of 12 and
18.
In January 2003, Prozac became the only SSRI approved by the FDA
for use in children 8 to 18 with major depression; psychopharmacologists
believe, however, that all the serotonin reuptake inhibitors act
similarly enough that safety and effectiveness proved for one can be
presumed of all. Many of the SSRIs have been studied and approved for use
in children with obsessive-compulsive disorder and other anxiety
conditions.
The latest concerns with SSRIs stem less from clear evidence of
risk than a paucity of placebo-controlled studies proving benefit against
depression in children. In strong contrast to the situation with adult
depression, the number of studies of antidepressants in children can be
counted on one’s fingers. It took an act of Congress in 1997, with
the provision of financial incentives to pharmaceutical manufacturers, to
encourage them to study their own drugs in children.
The current alarm was tripped when three unpublished studies failed
to demonstrate any benefit of Paxil versus placebo in depressed children.
Child psychiatrists are quick to put that in perspective. “Ten
years ago, we were still debating whether kids could be depressed,”
says Robert Kowatch, M.D., professor of psychiatry and pediatrics at
Cincinnati Children’s Hospital and Medical Center. “The early
studies we did were not well designed.”
Timothy Wilens, M.D., associate professor of pediatric psychiatry
at Harvard, elaborates. “Only recently have psychiatrists become
familiar with ways to assess childhood depression.”
What’s more, many observers believe that a variety of
responses “got lumped into the ‘adverse reaction’
category.” According to Wilens, the primary problem is the
emergence of “fleeting suicidal ideation.” He emphasizes that
no actual suicide “events” have been tied to such
reactions.
What is clear is that a number of people have transient reaction to
medications. It could be manic activation. It could be activation of some
psychotic features. In his own study, Wilens says, “we didn’t
find any de novo suicidal ideation. The drugs are probably triggering
panic and other reactions interpreted as suicidal ideation.”
Clinically, Kowatch says, there a 2% risk of any adverse effect.
“Most of the time a kid who shows up in a psychiatrist’s
office with depression has been through psychotherapy. He or she is
failing in school and is suicidal. We’re willing to take that risk.
Nine out of ten will do well with an antidepressant, though not
necessarily the initial one tried. I may have to switch to find the right
one.”
Kowatch contends that American psychiatrists are more comfortable
with SSRIs and medications in general than are their British
counterparts. “There is a cultural difference; they are still
debating whether depression appears in children.”
Tags:
alert safety,
antidepressant medications,
case reports,
cause of death,
childhood depression,
control group,
controlled trials,
depression,
impulsive behavior,
leading cause of death,
medical journals,
nuanced approach,
safety concerns,
serotonin reuptake inhibitors,
ssri,
SSRIs,
stage in life,
suicidal thoughts,
suicide,
suicide attempts,
untreated patients
