Neither aggregate suicide rates nor the individuals who commit suicide, are predictable, and no intervention has ever been proven effective against an individual taking his / her own life.
But suicide—or rather the marketing of suicide prevention—has become a Big Business . Depressed sales of antidepressants (in the wake of FDA’s required Black Box label warnings about an increased risk of drug-induced suicidality) pose a threat to that business. Depressed sales may be the (unacknowledged) catalyst for numerous studies whose scientific method may be dubious but whose conclusions support the drugs’ benefit as a suicide prevention salvo.
The authors of an article in PLoS Medicine claiming that Prozac “may have contributed to the prevention of as many as 33,600 suicides since the drug was introduced,” declare that “no competing interests exist" . Both the claims are challenged below.
The conundrum for industry and psychiatry is lack scientific evidence to support the safety and effectiveness of these drugs: First, the exceedingly high placebo effect (80%) demonstrated in controlled clinical trial data submitted to the FDA  ; and second, severe adverse effects—including a twofold increased risk of suicidal behavior—now acknowledged on the drugs’ label. These negative facts have led psychiatrists whose career is invested in the drugs to turn to epidemiological data  . But such studies are not valid to answer the clinical question: is the risk / benefit ratio of antidepressants favorable for patient use?
Furthermore, a legitimate epidemiological study in the Journal of the American Medical Association  compared U.S. suicide statistics during a 10 year period (between 1990-1992 and 2001-2002). The finding: "Despite a dramatic increase in treatment, no significant decrease occurred in suicidal thoughts, plans, gestures, or attempts in the United States during the 1990s." The authors note: "There are approximately 3000 suicide ideators per 100 000 population and 500 suicide attempters per 100 000 population in the United States each year compared with only 14 suicide completers per 100 000 population." Since increased treatment did not reduce suicide thoughts, gestures and attempts–which are far more prevalent than completed suicides–one cannot justifiably attribute the 6% drop in completed suicides during that 10 year period to the increase in treatment.
Nevertheless, UCLA psychiatrists, led by Dr. Julio Licinio, make precisely that claim: “Our findings strongly suggest that these individuals who committed suicide were not reacting to their SSRI medication. They actually killed themselves due to untreated depression. This was particularly true in men and in people under 30. My concern is that when people don’t get the treatment they need, the suicide rate is going to go up again" .
Those claimed findings are refuted by a case control study (2006) conducted by Drs. Mark Olfson and David Shaffer , prominent Columbia University psychiatrists who endorse the use of these drugs. Their study, however, confirmed the risk whose denial for over a decade has been the cause of a contentious debate. Their findings, they noted, validated FDA’s warnings:
“Children and adolescents treated with an antidepressant medication were significantly more likely to attempt suicide than those who were not treated with an antidepressant drug.” Furthermore, Drs. Olfson and Shaffer confirmed that “Children and adolescents who were treated with an antidepressant drug were significantly more likely to complete suicide than children who were not treated with an antidepressant drug (OR, 15.62; 95% CI, 1.65-infinity)”
In their latest much publicized epidemiological study published in PLoS Medicine, June 2006 , the UCLA authors noted that FDA’s required “black box warning” on antidepressant labels made it "timely to examine temporal trends in suicide and to study the potential impact of antidepressants on mortality caused by self-harm." They examined U.S. Census and CDC statistics since 1960, comparing the suicide rate before introduction of Prozac (1988) and after that date until 2002. From these statistics they extrapolated a relationship between increased use of SSRI antidepressants and reduced suicide rates since 1988. But aggregate epidemiological studies such as this are scientifically least valid to prove a cause and effect relationship resulting in an individual’s action.
Indeed, the authors acknowledge that “causal associations cannot be established with this type of observational data.” However, the conclusion they drew provided Eli Lilly with a widely publicized marketing pitch: “for the entire US population, a direct, inverse correlation exists between suicide rates and fluoxetine, and that treatment with fluoxetine (or possibly all SSRIs) for depression and other mood disorders may have contributed to the prevention of as many as 33,600 suicides since the drug was introduced”  http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030190 .
Their widely publicized claimed findings published in peer reviewed journals—by authors who “declared that no competing interests exist"—were clearly of great commercial value to manufacturers. Many in the media proceeded to broadcast the “good news.”     . United Press International medical reporter, Lidia Wasowicz, did not.
It isn’t often that a reporter seriously questions the validity of academic researchers’ claims about a causal relationship between use of antidepressant drugs and fluctuating suicide rates–Wasowicz does just that (below). She notes: “Numbers may never lie, but they rarely tell the whole truth.” She then shows how different studies assessing similar uncontrolled population data have led investigators to make speculative assessments and draw inconsistent conclusions.
When pressed by UPI reporter, Lidia Wasowicz about his scientifically inaccurate claim suggesting a causal connection, Dr. Licinio acknowledged: "you can’t say suicide rates went down because of antidepressants."
No competing interests exist?
Dr. Julio Licinio has been (is ?) the UCLA coordinator for the International Society of Pharmacogenomics (ISP) and editor of its journal, Pharmacogenomics. Notwithstanding the ISP website claim: "The International Society of Pharmacogenomics is an independent body without any affiliation to institutions, and without direct institutional/administrative ties to any companies," ISP listed the following current sponsors in 2003: Eli Lilly, Novartis, Pfizer, Wyeth, and Desert Pacific Healthcare Network. http://18.104.22.168/isp/la2003program.asp
In 2003, following ISP first meeting (October 2002, Paris), Dr. Licinio informed ISP members in a Newsletter how he actively sought funding for the ISP:
"I was able to obtain annual company sponsorships from GSK (which gave us $15,000 for the period 2002-2005 thanks to the generosity of Allen Roses), Eli Lilly (which gave us $5,000 for 2002) and Pfizer (which will give us $7,500 for 2003). Note that in $5,000 I requested annual unrestricted contributions from industry for $5,000 per year. I increased those amounts to be $7,500. This increase was due to the fact that as I look into the details of putting this meeting together, I see the actual costs of things, and the need to secure more funds. Also note that ISP now offers companies two types of corporate memberships: Founding Regular ($7,500 per year) and Founding Gold ($15,000 per year)." http://www.pharmacogenomicsociety.org/site/ISP-newsletter1.pdf#search=%22julio%20licinio%20ISP%20pfizer%22
According to RxPG News  Dr. Licinio, who moved from UCLA to The University of Miami Leonard M. Miller School of Medicine, “accepted an offer to consult for Eli Lilly after this research was accepted for publication.”
1. TeenScreen https://www.ahrp.org/cms/content/view/106/52/ ;
Screening for Mental Health (SMH) https://www.ahrp.org/cms/content/view/97/29/ ;
JED Foundation, a pharmaceutical industry front, operates as a suicide prevention program on college campuses, see: https://www.ahrp.org/cms/content/view/171/55/
2. Michael S. Milane, Marc A. Suchard, Ma-Li Wong, Julio Licinio. “Modeling of the Temporal Patterns of Fluoxetine Prescriptions and Suicide Rates in the United States,” PLoS Medicine, June 2006. http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030190
3. Irving Kirsch, Thomas J. Moore, Alan Scoboria, and Sarah S. Nicholls The Emperor’s New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration, Prevention & Treatment Volume Five July 15, 2002. Target article with 9 commentaries.
4. Joanna Moncrieff and Irving Kirsch Efficacy of Antidepressants in Adults, BMJ, 2005;331:155-157.
5. Olfson M, Shaffer D, Marcus SC, Greenberg T. Relationship between antidepressant medication treatment and suicide in adolescents. Archives of General Psychiatry. 2003 Oct;60(10):978-82, p. 979.
6. Julio Licinio quoted by WebMd, Suicide Rate Down Since Prozac, Feb. 2, 2005 http://www.cbsnews.com/stories/2005/02/02/health/webmd/main671167.shtml
Licinio and Ma-Li Wong, Nature Reviews Drug Discovery, February 2005; vol 4: pp 165-171.
7. Trends in Suicide Ideation, Plans, Gestures, and Attempts in the United States, 1990-1992 to 2001-2003 Ronald C. Kessler, PhD, Patricia Berglund, MBA, Guilherme Borges, PhD, Matthew Nock, PhD, Philip S. Wang, MD, DrPH. JAMA. 2005;293:2487-2495
8. Mark Olfson, Steven C. Marcus David Shaffer. Antidepressant Drug Therapy and Suicide in Severely Depressed Children and Adults: A Case-Control Study Arch Gen Psychiatry. 2006;63:865-872
Sample press coverage of PLoS article:
9. CBS News. Suicide Rate Down Since Prozac Feb. 2, 2005 http://www.cbsnews.com/stories/2005/02/02/health/webmd/main671167.shtml
10. Maggie Fox Depression drug suicide link challenged Reuters Wednesday, 14 June 2006 http://www.abc.net.au/science/news/health/HealthRepublish_1662666.htm]
11. US suicide rate drops as antidepressant prescriptions rise Jun 14, 2006, Reviewed by: Dr. Ankush Vidyarthi, RXPG News http://www.rxpgnews.com/medicalnews/healthcare/usa/article_4452.shtml
12. Jim Rosack Suicide Rates Began to Drop With Advent of SSRIs
Psychiatric News April 1, 2005 Volume 40 Number 7, p. 29.
123. An Extensive Database Search on Antidepressants and Suicide. Science Today, University of California radio, August 1, 2006 http://www.ucop.edu/sciencetoday/pages/archive/transcripts/2006/sci953.html
Contact: Vera Hassner Sharav
Ped Med: Can Rx’s cut suicide risk?
By LIDIA WASOWICZ
UPI Senior Science Writer
SAN FRANCISCO, Aug. 23 (UPI) — Some studies suggest as antidepressant use goes up, suicide rates among teens come down — but critics contend this does not prove the medicines save lives.
One review of records dating back to 1960 showed following a 28-year climb that peaked at nearly 13 self-inflicted deaths per 100,000 men and women in 1988 — the first year of a treatment revolution instigated by the introduction of the antidepressant Prozac — the suicide rate started descending. It hit rock bottom at 10.5 per 100,000 in 2002, the last year covered by the study.
Numbers may never lie, but they rarely tell the whole truth.
Who’s to say, for example, the decline noted in the analysis was not due to some other factor, such as the more-or-less simultaneously enacted legal restrictions on access to guns — the weapon of choice for suicide, question critics like patient rights advocate Vera Hassner Sharav.
"You can’t say they (suicide rates) went down because of antidepressants," Licinio acknowledged, "but it’s hard to make a case that antidepressants are causing suicidality because the suicide rate is going down."
Here again, upon closer inspection, uncertainty bedevils any definitive conclusions.
The investigators did not separately examine suicide rates in minors, which do not uniformly reflect the general trends.
Consider the twists and turns the tale takes when you take a look at government statistics broken down by age.
True, the federal figures show between 1980 and 1992, the number of suicides declined in the under-25 demographic as a whole, from 5,381, or 5.7 per 100,000 individuals, to 5,007, or 5.4 per 100,000.
However, during the same period, the rate shot up, by a solid 28.3 percent, from 8.5 to 10.9 per 100,000, among teens 15 to 19 — and by a mind-blowing 120 percent, from 0.8 to 1.7 per 100,000, among children 10 to 14.
It was not until 1994 that the rate in minors began to dip, reaching 7.4 per 100,000 for those 15 to 19 in 2002, the lowest rate for this age group since the 1970s.
Across college campuses, the number of young people seriously contemplating, attempting or committing suicide appears to be inching up.
In a 2004 poll of 1,865 students at four large universities, 24 percent said they had considered ending it all before graduation. That’s a strikingly higher number than the 8.5 percent reported in a similar 2001 study and 9.5 percent noted in a 2000 analysis.
A similar disparity was found in the rates of suicide attempts, reported by 5 percent of the students in the 2004 survey — disturbingly higher than the 1 percent and 1.5 percent, respectively, so inclined in the two earlier investigations.
"This is one of the most significant findings of this study," lead author John Westefeld, counseling psychology professor at the University of Iowa College of Education, wrote in his conclusion.
However, the findings may simply reflect students’ increased willingness to report attempts, he added.
"The reality is we don’t know the answer to these questions," said Richard McKeon, the government’s special expert on suicide prevention.
"(There are) some people who feel the youth suicide rate peaked in the late 1980s, then plateaued, then began to come down modestly in the 1990s," he noted.
"Some people … argue this may be due to increased utilization of antidepressants, especially SSRIs. Others disagree," McKeon added. "We don’t know for sure what’s responsible for those changes in suicide rates."
Whatever the reason, McKeon said, "I think it’s prudent clinical practice that children who are put on high-risk kinds of antidepressants need to be carefully followed, especially in the days after they’re prescribed."
Key questions remain even after the completion of what many in the field consider the most important report published to date on the treatment of depression in teens, dubbed TADS.
The Treatment of Adolescent Depression Study found among the 439 participants, ages 12 to 17, a type of psychotherapy known as cognitive-behavior therapy combined with Prozac quelled symptoms of depression more effectively than either treatment alone or than a sugar pill.
The strategy teaches problem-solving and helps fight negative thoughts. On its own, neither the drug nor the talk therapy worked better than the placebo. However, all three treatments proved superior to the sugar pill in subverting suicidal notions.
Although the investigators found no close ties between suicide attempts and SSRI use, they did note a much higher rate of "harm-related events" in the Prozac-taking patients than in the other groups.
These included self-cutting, though not necessarily with the intent to die, suicidal ideas and destructive thoughts or acts aimed at people or property.
Another study, a government-sponsored survey of 9,708 men and women 18 to 54 that compared U.S. suicide data between the periods 1990-1992 and 2001-2003, further muddied the picture of the drugs’ effectiveness in preventing suicidal behaviors.
The report, published in the Journal of the American Medical Association, provided antidepressant antagonists with ample ammunition to press forward with their questions about the drugs’ ability to stop users from considering, planning or attempting suicide.
The authors from Harvard University, Brigham and Women’s Hospital, University of Michigan and the Mexican Institute of Psychiatry concluded. "Despite a dramatic increase in treatment, no significant decrease occurred in suicidal thoughts, plans, gestures or attempts in the United States during the 1990s."
They expressed uncertainty about the role, if any, the drugs played in defusing death-inviting despair during the decade studied.
"Completed suicides decreased by about 6 percent during this period," they wrote. "The increase in treatment might have played a part in this trend, although county-level analysis shows no overall association between amount of treatment, as indicated by per-capita number of antidepressant prescriptions, and the suicide rate."
"If increased treatment did play a part in the decrease in the suicide rate, then why did we not see a comparable decrease in suicide-related behaviors?" the study authors wondered.
"Randomized controlled trials find only modest effects of treatment in reducing suicidality, even with optimal regimens," they concluded.
They recommended increasing outreach to untreated suicidal individuals and improving the effectiveness of treatments.
Next: Out-of-bounds treatments.
(Editors’ Note: This series on depression is based on a review of hundreds of reports and a survey of more than 200 specialists.)
UPI Consumer Health welcomes comments on this column. E-mail Lidia Wasowicz at firstname.lastname@example.org
See other articles in this UPI series:
Ped Med: Antidepressant use needs watching < (August 21, 2006) — Whatever the views on treating sad adolescents with antidepressants, everyone agrees all minors taking the pills should be closely watched for signs … > full story <http://www.sciencedaily.com/upi/index.php Ped Med: Drug warning sparks debate <http://www.sciencedaily.com/upi/index.php > (July 18, 2006) — It’s been nearly two years since a strong warning of increased risk of suicidal thoughts and behaviors was slapped onto antidepressant labels, … >
Ped Med: Depression treatment choices <http://www.sciencedaily.com/upi/index.php <http://www.sciencedaily.com/upi/index.php ?feed=Science&article=UPI-1-20060712-15132000-bc-pedmed-depression-14.xml> > (July 12, 2006) — When it comes to treating depression, it’s a matter of different strokes for different folks, specialists say. No remedy will suit all … > full story <http://www.sciencedaily.com/upi/index.php >
Ped Med: The anti-depressant dilemma <http://www.sciencedaily.com/upi/index.php > (June 21, 2006) — With the older tricyclic anti-depressants generally deemed unsuitable for the young and depressed, treatment of this age group most often relies on … > full story <http://www.sciencedaily.com/upi/index.php >
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