Fluoxetine - AKA Prozac
Paroxetine - AKA Aropax, Seroxat, Paxil
Study ID -
29060/356
A double-blind, multicentre study to compare paroxetine and fluoxetine in the treatment of patients with major depressive disorder with regard to antidepressant efficacy, effects on associated anxiety and tolerability.
Snapshot was taken 3rd September 2018
Study ID -
29060/356/_1
Extension phase for a double-blind, multicentre study to compare paroxetine and fluoxetine in the treatment of patients with major depressive disorder with regard to antidepressant efficacy, effects on associated anxiety and tolerability.
Both studies appear on the GSK Study Register website, the second study is a continuation (extension) of the first.
As you can see, both studies were double-blind, which means neither the patient or investigator knew what drug they were taking/prescribing. After the trials have been completed, GSK can break the code and find out on which drug the adverse events occurred. In this case, one suicide in the paroxetine group and one in the fluoxetine group; no suicide attempts in the paroxetine group, and; two in the fluoxetine group, one of which was a completed suicide. In both groups, there was one suicide each, both were women.
According to recently obtained documents from the Therapeutic Goods Administration (TGA), the #356 trial reported 7 suicide attempts* (2 of which were completed suicides). However, there is no mention of the 5 attempted suicides on the GSK Study Register website, at least not for paroxetine. They do, however, cite two suicide attempts for patients taking fluoxetine during the trial, one of which was a completed suicide.
*Further, more documents show that there were in fact 9 suicide attempts in Study #356, however, there is no mention of this on the GSK Study Register website.
Masking the suicide attempts
GSK report that there were 6 subjects with non-fatal serious adverse events (SAEs) in the paroxetine group and 10 in the fluoxetine group. A total of five (2 paroxetine, 3 fluoxetine) are in the Drug Abuse (Overdose) category.
Drug overdoses
Could these be deemed as attempted suicides or were the overdoses unintentional? If, indeed, they were attempts at ending one's own life, then why is it not reported as such? Well, according to recently obtained documents, no suicide attempts were made by overdose.
Therapeutic Goods Administration (TGA)
Who are the TGA?
The TGA is Australia's regulatory authority for therapeutic goods. They carry out a range of assessment and monitoring activities to ensure therapeutic goods available in Australia are of an acceptable standard. They are the American equivalent of the FDA and British equivalent of the MHRA.
The Previously Unseen Documents for Study ID - 29060/356
These were obtained under the Freedom of Information Act and forwarded to me by 'Kathy' who runs the
Australian Antidepressants Class Action & Awareness Facebook page. Kathy copied me in on a lot of the correspondence between herself and the TGA. The process of obtaining the following documents took a considerable amount of time; I'd estimate the best part of a year. Kathy's tenacity and doggedness paid off.
After initially requesting payment for the documents, the TGA apparently had a change of heart and released many documents pertaining to Study #356, most of which make for very interesting reading. Before I publish them, it's important you understand the reasons why there are many redactions (black-outs) in the documents. According to the Australian Freedom of Information Act 1982, there are a number of exemptions where certain information may be redacted. They include: protecting patient privacy; irrelevant material; documents disclosing trade secrets or commercially valuable information and; documents subject to legal professional privilege.
Human Research Ethics Committees (Australia)
It may be unethical for a researcher to continue a trial if:
(a) there are or have been substantial deviations from the trial
protocol;
(b)
side effects of unexpected type, severity, or frequency are
encountered
National Statement on Ethical Conduct in Research Involving Humans
You'll hear more about the Human Research Ethics Committees (HREC) in the documents below.
First off, the two suicides...
32-year-old female
Causality: "Possible"
Outcome: Death, maybe drug
46-year-old female
Causality: "Possible"
Outcome: Death, maybe drug
Attempted Suicides
According to the study posted on the GSK website, there were only two suicide attempts, both of which occurred in the fluoxetine group. One of these was fatal. However, the documents obtained from the TGA say something quite different. There is a contradiction as to exactly how many suicides attempts occurred. Firstly, according to a Paroxetine Clinical Study Meeting, Dr Sykes claimed there were 9 reported suicide attempts, two of which were completed suicides.
The study meeting, according to the document, was held on Friday the 26th of November, 1993
However, 4 months prior to Dr Sykes' claims, GSK, then SmithKline Beecham, sent a letter to all investigators involved in the trial. They stated,
"...we have now received reports of 7 suicide attempts (including two deaths) for the 356 study comparing paroxetine to fluoxetine."
The letter, below, goes on to state how confident they are that,
"the number of suicide attempts in this study is within that expected as a consequence of the depressive illness per se."
In other words, it wasn't the drug, it was the illness.
In between these two letters, we have a document from a Professor (dated September 1993). The letter was sent to the Research Ethics Committee.
GSK had made contact and told him about the suicides and suicide attempts. Here it gets interesting because it gives us the number of those enrolled (63). The Professor states, "...there have been seven suicide attempts including two deaths in the first 63 patients included in this Australian multicentre study." (11.11%)
The letter,, signed off by an Associate Professor at the School of Psychiatry, goes on to say how he had researched data and had found no evidence that either paroxetine or fluoxetine increase suicide rate or ideation in depressed patients. Remember, this was 1993 - no lawsuits had yet revealed the extent of those who had died or attempted suicide on paroxetine, or indeed Prozac.
In November 1993, the Research Ethics Committee ceased enrollments for the study because of the "reported cases of suicidal gestures'. A review of the attempted suicides was needed before #356 could proceed.
#356 was halted and, it seems, an independent review of the study took place one year later. The independent review clarifies that there were actually nine suicide attempts, two of which were successful. In all, according to the review, there were 100 patients enrolled. The review, however, found no reason why the study shouldn't continue. (Attempted suicides = 9%)
Of the 91 patients who did not attempt suicide, the review states, "26 either withdrew or were withdrawn prematurely from the trial." No reason is given for this.
According to the review, no suicide attempts were made by means of a drug overdose.
Comment
Where are these missing suicide attempts? Why are they not reported on the GSK Study Register website?
There were 7 suicide attempts when 63 patients were enrolled (11.11%) . Surely this figure should have raised a red flag?
There were 9 suicide attempts when 100 patients were enrolled (9%) . Even this figure is astronomically high.
Investigators and review panels didn't really have much to go on back in 1993/94, apart from, of course, GSK's own information and published literature that was mainly ghostwritten by PR companies hired by GSK.
From the early onset of this study, GSK made it abundantly clear to investigators (prescribers) that there was no supporting evidence that suggested paroxetine could induce suicidal ideation. The study was double-blind so the patients and investigators didn't know what drug was being used.
Today, on the GSK Study Register website we see that since the study completion, GSK broke the code (so they could see what patient took what drug). They admit to having one suicide in the paroxetine group and one in the fluoxetine group. What they don't do, and they've had 25 years to rectify, is show us what drug caused the suicide attempts. According to the findings, we see no attempts in the paroxetine group and 2 (one completion) in the fluoxetine group. This would suggest that they also broke the code for the suicide attempts but only showed 2 (both in the fluoxetine group) when the documents obtained from the TGA show that there were 7 attempts when 63 patients were enrolled and 9 attempts when the enrollment reached 100.
The 356 Study that sits on the GSK website today doesn't really raise any red flags in its current format. With documents I've published today should we have a need to be concerned?
It is unknown in what group the non-fatal suicide attempts occurred. For all we know they could have all occurred in the fluoxetine group. I'm unsure why GSK have omitted such important data but I can speculate.
It leaves me wondering that if such a trial was carried out today, would the review board still claim there is no link between either paroxetine or fluoxetine and suicidal ideation?
Since the year of this #356 study (1993) GSK has paid $390 million for suicides or attempted suicides said to be linked to paroxetine. This has included an average of $300,000 to resolve 300 attempted suicide cases and an average of $2 million for 150 suicide cases. (
Source)
The most recent paroxetine suicide case involves former corporate lawyer Stewart Dolin, whose life ended when he jumped in front of a Chicago Transit Authority train on July 15, 2010, while taking a generic version of Paxil. On April 20, 2017, an Illinois federal jury
found GSK liable for Stewart Dolin’s death and ordered the pharmaceutical company to pay $3 million to Wendy Dolin. However, on August 22, 2018, the Seventh Circuit Court of Appeals
overturned the verdict claiming,
"GSK had presented sufficient evidence time and again through the proceedings – before, during and after trial – to demonstrate it had no control of the drug labeling at the center of the case. Therefore, they said, the lawsuit should have been dismissed." Further, they added, "Court judges erred when they allowed to go to trial a lawsuit brought by Stewart Dolin's widow (Wendy Dolin)"
By 2000, Eli Lilly had reportedly paid more than $50 million to settle more than 30 Prozac (fluoxetine) lawsuits related to murders or suicides. There were also undisclosed settlements. While Prozac suicide lawsuits spiked in the 1990s, Lilly faced less litigation after the drug lost patent in 2001 and generics flooded the market. An FDA-required black box warning for suicide ended all “failure to warn” lawsuits. (
Source)
Bob Fiddaman
Special thanks to 'Kathy' of the
Australian Antidepressants Class Action & Awareness Facebook Group
Kathy is also an administrator for the
Australians For Safe Medicines Facebook page.
She is now in the process of requesting suicide information from Venlafaxine trials in Australia.
