By Steven Daviss, MD
[Summer 2007; Vol. 33, No. 3; Pg. 5, 14]
Neil
Sandson asked me to take over the Psychopharmacology Column in which he focused
mostly on drug interactions and metabolism. This area is one of my
interests, as well, but I plan to broaden the discussion, which may take us into
other areas, including standard prescribing practices, managing side effects,
FDA actions, and policy and legislative issues around medications. Please
let me know about specific issues you would like to see discussed in this column
by emailing me at: sdaviss@comcast.net.
The
FDA recently announced that "In December 2006, FDA's Psychopharmacologic
Drugs Advisory Committee agreed that labeling changes were needed to inform
health care professionals about the increased risk of suicidal thinking and
behavior in younger adults using antidepressants. The committee also noted that
product labeling needed to reflect the apparent beneficial effect of
antidepressants in older adults and to remind health care professionals that the
disorders themselves are the most important cause of suicidal thinking and
behavior." The new labeling will soon be released by all
antidepressant drug manufacturers.
These
changes should have a significant impact on depression management, particularly
in primary care practices. The warning language in the black box will now
indicate, "Antidepressants
increased the risk compared to placebo of suicidal thinking and behavior (suicidality)
in children, adolescents, and young adults in short-term studies of major
depressive disorder (MDD) and other psychiatric disorders... Short-term
studies did not show an increase in the risk of suicidality with antidepressants
compared to placebo in adults beyond age 24; there was a reduction in risk
with antidepressants compared to placebo in adults aged 65 and older. Depression
and certain other psychiatric disorders are themselves associated with increases
in the risk of suicide. Patients of all ages who are started on antidepressant
therapy should be monitored appropriately and observed closely for clinical
worsening, suicidality, or unusual changes in behavior. Families and caregivers
should be advised of the need for close observation and communication with
the prescriber."
What
is ground-breaking about this new language is the fact that a black box
warning--for the first time--advises that there is a DECREASED risk of an
adverse event. The Advisory Committee had recommended even stronger
language to indicate the "protective effect" of antidepressants
against suicidal thoughts and behaviors for older folks, particularly seniors.
The final version will be more obtuse, however, putting the data in the form of
a chart. The chart will indicate, by age group, the number of
additional--or fewer--episodes of "suicidality" per 1000 treated cases
(compared with placebo), as follows:
<18 14 additional cases
18-24 5 additional cases
25-64 1 fewer cases
>64 6 fewer cases
Some
of the possible explanations discussed at the December meeting for the biphasic
nature of the data (higher risk when younger, lower risk when older) included
induction of mania, late maturation of frontal lobes so impulsivity and
experience improve as you get older, and greater tolerance for uncomfortable
affect with age. The committee also felt it was very important to
emphasize the need for close follow-up when treating people of any age with
depression. There was concern that it could sound like older people don't need
to be followed as closely due to this "protective effect".
There
will also be additional language to address the emergence of the so-called
"activation syndrome". The language will advise prescribers to
tell family members and caregivers to "monitor
patients for the emergence of agitation, irritability, unusual changes in
behavior, and the other symptoms described above, as well as the emergence
of suicidality."
This
emphasis on close observation may lead to a loosening of managed care
restrictions about the frequency of outpatient follow-ups. There is also
an emphasis on communication with the family, which is always a good practice.
An unintended consequence may be increased liability if documentation in the
medical record lacks such communication.
Psychiatrists
already practice these important elements of depression monitoring--frequent
follow-up, monitoring for symptom changes and adverse effects, and obtaining
collateral information sources. The most important benefit of the FDA's
labeling changes may eventually be the widespread adoption of these principals
by primary care physicians. "Take this pill and return in a
month," may become a thing of the past.
The
FDA acknowledged concern about telling doctors how to practice, and crossing the
line into federal regulation of the practice of medicine. However, it was
pointed out that when the stakes are high enough, as with clozapine, the FDA has
had no trouble advising things like frequency of monitoring lab tests. Telling
prescribers that people with depression starting antidepressants should be
followed at least weekly at first should be no different.
Notable
quotes from the Advisory
"Maybe
we don't need a black box on Antidepressants. Maybe we need a black box on
Depression."
"How
many will die with the black box? How many will die without it?"