Selective Serotonin Reuptake Inhibitor anti-depressants (S.S.R.I.'s) hit the market in 1988. Immediately, reports of intense suicidal thoughts and actions while taking these drugs began to flood into the F.D.A.. Despite the reports, and data indicating a higher rate of suicides from those using the drugs than from those using placebos, it took about twenty years for the F.D.A. to issue a warning about the risk.
The warning was considered a victory to many who had lost loved ones to S.S.R.I. drugs. Public perception was that the F.D.A. had stood up to Big Pharma and forced reluctant S.S.R.I. manufacturers to issue an appropriate warning. Thereby, solidifying the perception of the F.D.A.'s role as advocate for the public.
However, this perception has been shattered by a recent federal court ruling that exposed a dirty little secret that the F.D.A. likely hoped would never come to light. In Dobbs v. Wyeth Pharms., the court determined that the F.D.A. repeatedly prevented at least one S.S.R.I. manufacturer from issuing a suicide-related warning for fear that it might "reduce the use of anti-depressants and thereby undermine the benefit of their use in treating depression."
The ruling stems from a lawsuit brought by the widow of a man who was believed to have committed suicide as a result of taking Effexor. The lawsuit accused Wyeth Pharmaceuticals of failing to properly warn patients that Effexor may increase the risk of suicide.
In its defense, Wyeth presented evidence that it had, on three separate occasions, attempted to institute a more "extensive suicide warning", but the F.D.A. had refused to approve each proposed warning.
Wyeth's first attempt occurred on September 25, 2002, when it submitted to the F.D.A. the results of seven Effexor pediatric studies, accompanied by a proposed label alteration describing the rate of suicidality events for children. The F.D.A. rejected Wyeth's proposed label alteration, which would have warned parents of the risk to their children, and then it directed Wyeth to only add the label change proposed by the F.D.A.. The F.D.A. added, "we do not feel that it would be useful to describe these negative trials in labeling, since this may be misinterpreted as evidence that [Effexor] does not work in this population."
The second attempt occurred in August 2003, when Wyeth amended its product label to caution patients about increased reports of "suicide related adverse events such as suicidal ideation and self harm" in pediatric patients.
The F.D.A. ordered Wyeth to remove the language included in the enhanced label warning and to substitute F.D.A. language that was applicable to all S.S.R.I.'s at that time. According to the F.D.A., it did so because it did "not believe that a causal association has yet been definitively established." Never mind that Wyeth's own internal studies (from the manufacturer) indicated sufficient cause for a warning.
Undeterred, Wyeth made a third and final attempt to include a warning about suicide on its drug label. It revised the language contained within its warning, and asked the F.D.A. to allow Effexor's label to continue to include a pediatric precaution.
On May 13, 2004, the F.D.A. ordered the removal of Wyeth's warning. By that time, the F.D.A. had finally admitted that sufficient evidence existed to support a warning about medically-induced suicides, but it required that Wyeth, and all other S.S.R.I. manufacturers adopt the specific language dictated by the F.D.A. rather than use the warnings proposed by the manufacturers.
The whole affair was managed like a public relations campaign, whereby the F.D.A. was presented as the organization leading the charge for labeling that would protect children; when in fact, it was actually the agency that had always suppressed such information, while essentially operating a protection racket for select pharmaceutical companies for roughly 20 years.
Other S.S.R.I. manufacturers have attempted to escape liability by arguing that the F.D.A. would not have permitted them to issue suicide warnings prior to 2004. However, those claims ultimately failed because the manufacturers could not establish that they had made any effort to issue a warning. Wyeth is the first to conclusively prove that the F.D.A. blocked a proposed warning.
As a result, the federal court dismissed the failure to warn claim against Wyeth. However, the case was permitted to proceed, due to additional claims.
Whose Side is the F.D.A. On?
To Wyeth's credit, it is the only S.S.R.I. manufacturer to propose a suicide warning prior to the issuance of the Black Box warning in 2004. Wyeth is also the only S.S.R.I. manufacturer to list "homicidal ideation" as an adverse event on its product label. All other S.S.R.I. manufacturers are vehemently opposed to the issuance of such warnings.
By rejecting Wyeth's proposed warning, the F.D.A. was serving the interests of the other S.S.R.I. manufacturers. Had Wyeth succeeded in issuing a warning for Effexor, other S.S.R.I. manufacturers would have been forced to follow suit.
The F.D.A.'s purported concern that the warning "may be misinterpreted as evidence that [Effexor] does not work in [children]" was nothing more than a smoke screen. S.S.R.I.'s have never been approved for, nor shown to be any more effective than placebos in treating children, with the exception of Prozac. (Prozac's effectiveness is only slightly above that of placebos.) However, despite these facts, millions of children continue to be prescribed S.S.R.I. drugs "off label."
The F.D.A was not so concerned about the public misinterpreting the lack of efficacy within this class of drugs, as it was with the public discovering their lack of efficacy.
The primary concern for S.S.R.I. manufacturers, and F.D.A. officials with financial ties to S.S.R.I. manufacturers, was the effect that an honest suicide warning would have had on pediatric prescription rates. Fewer children being prescribed S.S.R.I.'s would have meant less profits for the drug companies, and less lucrative drug approvals.
As it turns out, the F.D.A.'s fears were prophetic. According to a Medco analysis, the rate of children who received anti-depressant prescriptions fell about 16% in the months following the issuance of the Black Box warning.
In the end, the F.D.A. saved S.S.R.I. manufacturers millions, if not billions of dollars by delaying the issuance of a suicide warning. It also cost countless children their lives.
When it comes to S.S.R.I.'s, the F.D.A. has repeatedly chosen Big Pharma interests over the safety of the public; profits over people.
Perhaps the most ironic and heartbreaking aspect of the story is that parents who had lost their children to S.S.R.I.'s actually broke down in tears, and thanked F.D.A. officials for issuing the F.D.A. Black Box warning in 2004.
Well orchestrated, indeed.
Dobbs v. Wyeth Pharms., 2011 U.S. Dist. LEXIS 79140 (case no. CIV-04-1762-F)