A pair of recent studies have independently come to the same conclusion on
the relationship between antidepressant prescribing and suicide rates. As
prescribing of medications—especially newer
antidepressants—increases, suicide rates go down.
Researchers at the UCLA David Geffen School of Medicine and the UCLA
Neuropsychiatric Institute completed an extensive review of data and
literature and concluded that suicide rates have declined steadily since the
introduction of newer reuptake inhibitor antidepressants in 1988. While not
proof, they said, the data strongly suggest that a direct relationship exists
and that most persons who did commit suicide did so because of untreated
In another analysis, researchers at the Center for Health Statistics at the
University of Illinois at Chicago (UIC) and Columbia University/New York State
Psychiatric Institute determined that increases in prescriptions for SSRIs and
other newer atypical antidepressants are associated with lower suicide rates
on a county-by-county basis across the United States.
The intricate analysis of National Vital Statistics data, provided by the
Centers for Disease Control and Prevention, linked that county-level suicide
data to county-level antidepressant prescribing data from IMS Health Inc., a
company that tracks prescription data worldwide.
The UIC/Columbia group concluded that "lower suicide rates both
between and within counties over time may reflect antidepressant efficacy,
compliance, a better quality of mental health care, and low toxicity in the
event of a suicide attempt by overdose."
"Our findings strongly suggest that... individuals who committed
suicide [while prescribed an antidepressant] were not reacting to their SSRI
medication," Julio Licinio, M.D., a professor of psychiatry and
endocrinology at UCLA and the lead author of the UCLA study, said in a written
statement. "They actually killed themselves due to untreated
The analysis, funded by grants from the National Institute of General
Medical Sciences and the Dana Foundation, appeared in the February Nature
Reviews Drug Discovery.
"The recent debate has focused solely on a possible link between
antidepressant use and suicide risk, without examining the question within a
broader historical and medical context," Licinio explained. "We
feared that the absence of treatment may prove more harmful to depressed
individuals than the effects of the drugs themselves."
Licinio and his colleague, Ma-Ling Wong, M.D., who are co-directors of the
Center for Pharmacogenomics and Clinical Pharmacology at the Neuropsychiatric
Institute, conducted an extensive database search of studies published between
1960 and 2004 on antidepressants and suicide. The resulting list of studies
ranged from population-based analyses of nearly 160,000 patients exposed to
multiple antidepressants to smaller clinical trials involving one drug and
only several hundred patients.
The researchers then developed a comprehensive timeline of key regulatory
events relating to the medications. They also generated charts tracking
antidepressant use and suicide rates in the United States.
Licinio said they were surprised by what they found.
"Suicide rates rose steadily from 1960 to 1988, when Prozac
[fluoxetine], the first SSRI drug, was introduced," he said."
Since then, suicide rates have dropped precipitously, sliding from the
eighth to the 11th leading cause of death in the United States."
Intriguingly, while the actual numbers of suicides steadily increased from
1960 until the late 1980s and then leveled off, the suicide rate (per 100,000
population) rose between 1960 and the 1970s. Suicide rates peaked in the early
1970s and then fluctuated until the late 1980s, when they began a steady
decline (see charts at right).
Licinio added that the pair reviewed several large European and U.S.
reports in which "researchers found blood antidepressant levels in less
than 20 percent of suicide cases." This, Licinio said, implies that the
vast majority of suicide victims either never received treatment or were not
compliant with prescribed treatment at the time of their deaths.
The second recent analysis, led by Robert Gibbons, Ph.D., of UIC's Center
for Health Statistics, and suicide researcher J. John Mann, M.D., a professor
of psychiatry at Columbia and chief of psychiatric research at New York State
Psychiatric Institute, was published in the February Archives of General
Their analysis was funded by grants from the National Institute of Mental
Health, with the assistance of a grant in aid from Pfizer Inc., to purchase
prescription data from IMS Health.
Gibbons and Mann found that, overall, there was no significant relationship
between antidepressant medications and suicide rates. However, within classes
of antidepressants, SSRIs and newer atypical antidepressants were associated
with lower suicide rates. In comparison, they found a significant association
between higher rates of prescribing for older, tricyclic antidepressants
(TCAs) and higher rates of suicide. In their analysis they adjusted for age,
sex, race, income, and county-to-county variability in suicide rates.
Even after adjustment, the relationship between TCAs and higher rates of
suicide persisted, leading Gibbons and Mann to suggest that "a high
relative prescription rate of TCAs is not simply an indicator of limited
access to quality mental health care, but indicative that choice of treatment
The UIC/Columbia team said that their results, along with several previous
studies, indicate that "suicidal behavior correlates with inadequate
prescription of antidepressants, and from 1978 to 1997, the proportion of the
outpatient U.S. population with depression that received at least one
antidepressant prescription increased from 37.3 percent to 74.5
Mood disorders, they noted, accounted for 45 percent of antidepressant
prescriptions in 1997 and 59 percent by 2000. "So, both the proportion
and therefore the impact of more prescriptions on mood disorders are likely to
have been sustained over this limited period of time for which we have
The authors of both reports assessed the limitations of the databases with
which they worked. Medication-usage estimates based on outpatient data are
simply estimates, they noted, and suicide data are affected by variables such
as suicide definition, qualifications of medical examiners, and whether all
suspected suicide deaths in a particular population were investigated.
Numerous variables also interact in clinical trial data, and any conclusions
regarding suicidal or harmful thoughts or behaviors tied to antidepressants in
clinical trials have been subjected to numerous questions (see related article
on page 1).
Yet these independently completed studies came to similar conclusions. In
particular, said Gibbons and Mann, "despite potential variability,
strong associations between antidepressant prescription rates and suicide
rates were observed. Since the associations were in opposite directions for
TCAs versus SSRIs and newer non-SSRIs, this variability is not producing
What is clear, the UIC/Columbia team concluded, is that "the findings
of this study relate to associations in the data and not to causation.
Randomized, controlled trials in high-risk patients are still
An abstract of "Depression, Antidepressants, and Suicidality:
A Critical Appraisal" is posted online at<www.nature.com/cgi-taf/DynaPage.taf?file=/nrd/journal/v4/n2/abs/nrd1634—fs.html>.
An abstract of "The Relationship Between Antidepressant Medication Use
and Rate of Suicide" is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/62/2/165>.▪
Arch Gen Psychiatry200562165