Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration

Identification of an association between antidepressant drug use and
suicidal thinking and behavior in some adolescents in 2004 (1), and the
regulatory public health warnings that followed (2), sparked a debate in
the clinical community regarding the potential for discouraging
appropriate use of antidepressant drugs, with the unintended consequence
of eventually exposing more patients to the suicide risk associated with
untreated depression (3). Indeed, depression is a major risk factor for
suicide in adolescents and suicide is the third leading cause of death in
this age group (4). These concerns were strengthened by an uptick in the
U.S. rate of adolescent suicide, reported annually by the Centers for
Disease Control and Prevention (CDC), which occurred in 2004 (3).
Significant decreases in the level of antidepressant drugs prescription
for pediatric patients following the regulatory actions were also reported
(2,5). Promotional spending for antidepressant drugs, which may represent
one of many possible factors influencing prescribing, also declined
significantly from the first quarter of 2004 to the first quarter of 2007
(2).

Given the reported decline in antidepressant drug prescription, it is
important to have a second look at the national trends in youth suicide.
Six years later, we present recently released data from CDC to update the
clinical community on the overall trend of rates of suicide among
adolescents. Figure-1 shows that, in spite of the observed continued
decline in use of antidepressant drugs among adolescents in the same time
frame (2,3,5), the rate of suicide decreased in the same age groups after
the unexplained increase of 2004. In 2007, the most recent year with
available data, the rates were the lowest reported in 25 years.

The findings reported in this letter underscore the limitation of
using ecological population-based approaches and especially of relying on
a single year's data to draw strong conclusions and raise what may turn
out to be premature concerns. Caution should always be exercised in
interpreting data based on this type of evidence. Ecological data could
not establish a cause-and-effect association between antidepressant drug
prescribing and suicide rates, nor could such data determine if the
changes in antidepressant prescribing were due to depression not treated
with drugs, or prescribing of fewer antidepressants for other conditions.
While it is important to be vigilant for unintended consequences of
regulatory actions on drug availability and utilization, ecological data
may not be the best guide to whether drugs are being used appropriately in
a given patient population.

References:

1- Hammad TA, Laughren T, Racoosin J. Suicidality in Pediatric
Patients Treated with Antidepressants. Arch Gen Psychiatry 2006; 63:332-9.

2- Pamer C, Hammad TA, Yu Te, Kaplan S, Rochester G, Governale L,
Mosholder AD. Changes in US antidepressant and antipsychotic prescription
patterns during a period of FDA actions. Pharmacoepidemiology and Drug
Safety 2010; 19:158-174.

3- Gibbons RD, Brown CH, Hur K, Marcus SM, Bhaumik DK, Erkens JA,
Herings RMC, Mann JJ. Early Evidence on the Effects of Regulators'
Suicidality Warnings on SSRI Prescriptions and Suicide in Children and
Adolescents. Am J Psychiatry 2007; 164:1356-63.

4- Olfson M., Shaffer D, Marcus SC, Greenberg T. Relationship between
antidepressant medication treatment and suicide in adolescents. Arch Gen
Psychiatry 2003; 60: 978-82.

5- Libby AM, Orton HD, Valuck RJ. Persisting Decline in Depression
Treatment After FDA Warnings. Arch Gen Psychiatry 2009;66(6):633-9