Psychiatr News September 1, 2006
Volume 41, Number 17, page 2
© 2006 American Psychiatric Association
New Data Add to Puzzle About Antidepressant, Youth-Suicide Link
Jim Rosack
With new research pointing to a link between antidepressants and suicidal
actions in youth, clinicians struggle to find significance in the
findings.
A new report suggests that child and adolescent Medicaid patients who have
been treated for major depression in an inpatient setting and are prescribed
antidepressants may be at a significantly increased risk of a serious suicide
attempt or death in the 60 days following discharge, compared with similar
patients who are not prescribed antidepressant medications.
The relevance of the study is, however, open to interpretation in part due
to limitations of the study design, which did not rule out the possibility
that those taking antidepressant medication were more severely ill than those
not receiving medication.
"These findings," said the report's lead author, Mark Olfson,
M.D., M.P.H., a professor of psychiatry at Columbia University College of
Physicians and Surgeons and a researcher at the New York State Psychiatric
Institute, "serve to reinforce some of the concerns that have been
raised [regarding an association between antidepressants and suicidality] and
really emphasize the importance of paying close attention to changes in mood
and actions of severely depressed young people as they start antidepressant
medication."
For several years now, researchers have been striving to answer the
question of whether the possible association between antidepressant
medications and increased risk of suicidality in children and adolescents
extends beyond less-severe expressions of suicidal thoughts or behaviors to
serious suicide attempts requiring medical intervention—or ultimately to
suicide deaths.
Numerous reports have postulated that the expression of suicidal thoughts
and/or behaviors—such as those now addressed by the labeling mandated by
the Food and Drug Administration (FDA) accompanying all antidepressant
prescriptions—is a different phenomenon than serious suicide attempt and
completed suicide. Yet, it is still not clear whether the reported association
of the medications with FDA-defined suicidality crosses the hypothesized
divide between the two phenomena.
National Case-Control Sample
The study, which appeared in the August Archives of General
Psychiatry, analyzed data from the Centers for Medicare and Medicaid
Services' (CMS) national Medicaid Analytic Extract Files (MAEF). The MAEF
includes comprehensive claims data for Medicaid beneficiaries in all 50
states.
The work was funded by grants from the National Alliance for Research on Schizophrenia and Depression, the Agency for Healthcare Research and Quality, the American Foundation for Suicide Prevention, and a private foundation, the Carmel Hill Fund.
"This was a case-control study of children and adults in Medicaid in
which we completed four different analyses. We looked at two outcomes each, in
both adults and kids, using the same criteria for both groups," Olfson
told Psychiatric News.
Using the Medicaid claims data, Olfson and his colleagues started with a
study population of all patients aged 6 to 64 who had one or more
hospitalizations for the treatment of a depressive disorder between January 1,
1999, and December 31, 2000. They then narrowed the sample by excluding
patients who were pregnant, had bipolar disorder, schizophrenia, other
psychoses, mental retardation, or dementia/delirium. Finally, they refined the
cohort further to those beneficiaries who filled at least one prescription for
any medication during the two-year study period.
Suicide Attempts Defined
Cases were defined by a diagnostic claim for a suicide attempt that
occurred within 60 days following discharge from a hospital for the treatment
of major depression. The suicide attempt was further defined as a
self-inflicted injury or intentional overdose of medication serious enough to
result in treatment in either an emergency department or inpatient
setting.
A total of 784 cases with suicide attempts were then matched to 3,635
controls. Each case was matched to up to five control subjects based on date
of discharge from an inpatient stay for the treatment of major depression.
Matching was also based on age, sex, race/ethnicity, and state providing their
Medicaid services.
For suicide deaths, cases were defined as a death within 60 days of
discharge from a hospitalization for major depression. Date and cause of death
were cross-referenced between the Medicaid database and death certificate data
from the National Center for Health Statistics National Death Index. A total
of 94 cases with completed suicide were matched, using the same matching
criteria as used for suicide attempts, with 435 controls.
Finally, the study population of 4,948 cases and controls was divided into
two groups: those aged 18 and younger, and those aged 19 to 64.
Similar but unexpected Findings
Within the defined cases and controls, Olfson and his
colleagues—including noted suicide expert David Shaffer, M.D., chief of
the Division of Child Psychiatry at Columbia University Medical Center, New
York State Psychiatric Institute, and New York Presbyterian
Hospital—first looked for any association between suicide attempt and
whether the patient had been prescribed and dispensed an antidepressant
medication. Then they repeated the analysis for those who died by suicide.
In the adult group, Olfson's team found no significant association between
the medications and suicide attempts or suicide deaths. However, in the child
and adolescent group, antidepressants were significantly associated with both
suicide attempts and completed suicide.
Olfson and his colleagues found that patients in their study population who
filled prescriptions for antidepressant medications following an inpatient
stay for major depression were 1.52 times more likely to make a serious
attempt at suicide (263 cases matched with 1,241 controls) than similar
patients who were not prescribed antidepressants.
Patients who filled antidepressant prescriptions following an inpatient
stay were 15.62 times more likely to die by suicide (8 cases matched with 39
controls) than similar patients not prescribed antidepressant medications.
While the study's findings are similar to those found by other researchers,
Olfson said, he expected to find no real association between the medications
and suicide attempts or deaths in either children or adults.
Finding Meaning Is Difficult
Olfson is quick to note that case-control, observational studies have
significant limitations, often making it difficult to determine what the
findings really mean.
"There's always the nagging doubt with studies like this," he
said, "that even within this defined population of patients following
hospitalization for depressive disorder, those receiving antidepressant
medications may well have simply been more severely ill."
Olfson and his team did not have any data indicating the severity of
individual patients' symptoms, he noted. Severity was inferred by the
necessity for inpatient treatment for major depression. By limiting the
analysis to events within the first 60 days following discharge, Olfson added,
"in theory, all of the patients were in the same period of their
recovery from that index hospitalization."
David Fassler, M.D., an APA trustee and child and adolescent psychiatrist,
said the study "should be interpreted with caution. The methodology
doesn't allow us to draw definitive conclusions in either direction from the
results."
There are many intervening variables, Fassler told Psychiatric
News, that could explain the results, including the possibility that
patients with more severe symptoms were more likely to receive antidepressant
medications.
While numerous studies have found associations between antidepressants and
suicidality, Olfson noted there is no clear indication of what factors might
help clinicians predict which patients prescribed the medications might be at
increased risk versus which patients aren't at risk.
"There is a feeling among clinicians that a personal history or
family history of suicide attempt, or bipolar disorder, can increase risk of
future suicidal thoughts, behaviors, and actions," Olfson said. Also
helpful, and possibly predictive, is the patient's or family members' response
to antidepressant medications, especially in the first few weeks and months of
treatment.
"But, bottom line, I don't think at this point the research has done
much to give us clear a priori risk factors," Olfson concluded.
"Clearly, more research needs to be done to establish these or other
indicators as true risk factors."
"Antidepressant Drug Therapy and Suicide in Severely Depressed
Children and Adults" is posted at
<http://archpsyc.ama-assn.org/cgi/content/abstract/63/8/865>.
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