Chapter 47 The Draft

Am working on the draft of my story – it’s hard to try to encapsulate so much information. It’s also difficult to make so much corruption seem believable. Dr. Mercola presented an interview with Dr. Golomb in his latest newsletter, however, that supports much of what’s gone on with triazolam is widespread now, though perhaps not to the extent of the corruption involving triazolam.

Anyway – here’s the draft of the first part:

In 1969, Upjohn developed a new kind of benzodiazepine (the class of drug Valium, Xanax belong to) it hoped would be its dream drug in more ways than one. It was a sleeping pill with a very short half-life – it got out of the bloodstream fast (usually) and so it didn’t leave you groggy or hung over the next day. When the company’s pre-market trials, however, predicted nightmare rather than dream results, the company cooked the books to try to make that illusional dream seem a reality.

After harming more than a few human guinea pigs, before and after the drug came on the market, Upjohn’s tactics soon came out of the dream world and into the light.

The drug was SO dangerous and SO decidedly so, and so well documented to be so, you’d think it’d be history by now, wouldn’t you? But it’s not.

Though the deadly sleeping pill HALCION died in the UK and a few other countries in the early 1990s and had a near death experience in America soon afterward, it has been resurrected, revived, and is now basking in the glowing ads of “sleep sedation” dentists all over the country, better known now by its generic name, TRIAZOLAM.

Dentists promoting its use who got their training from an organization called DOCS, will likely not even bother to mention its less lethal name on their websites or in their ads.
They’ll more than likely inform you that “sleep dentistry,” more accurately labeled “oral conscious sedation,” is just so easy and safe – you just “take two little pills” and “forget you even had an appointment.” To find a DOCS dentist one simply needs to google “trained with some of the world’s top sedation dentists” or “rapidly becoming __’s leading sedation dentistry.”

MSNBC, rather than informing the public of the drug’s true nature and deadly, controversial past, for the most part got with the DOCS program, titling it’s piece on oral conscious sedation, “Pop Some Pills; Sleep Through Your Dental Appointment.”

John Coleman of Missouri went to sleep during his March, 2007 appointment and never woke up again. My daughter, less than half Coleman’s weight, was given half the dose he got, and she has never been the same person since. As a matter of fact, she has exhibited just about every symptom Cees van der Kroef observed in the late 70s in his patients in the Netherlands, where the drug was first marketed (along with Belgium). Our lives have been anything BUT a dream since.

Van der Kroef, a respected psychiatrist who worked with insomniac patients (whom dental researchers promoting triazolam like to refer to as psychiartric patients, to insinuate they were psychotic before they took the drug), had naturally offered this new drug to his patients with sleep issues, because of its short half-life and claims of being safer than other, long-lasting benzodiazepines (benzos).

M. N. G. Dukes, Vice Chairman of Netherlands Committee for the Evaluation of Medicines (CEM) at the time, later wrote that one of van der Kroef’s patients, a middle-aged lawyer, was so changed by the drug’s effects that she asked the doctor if he had given her LSD. The list of symptoms van der Kroef reported to the Netherlands’ CEM were not a surprise, said Dukes, because the agency was getting some of those reports as well, and since van der Kroef was already preparing to publish his paper in CEM’s journal, Excerpta Medica, on July 6th, 1979, the agency felt his action, along with their report to Upjohn of “preliminary impressions” would be sufficient. (M.N.G. Dukes, ed. “Side Effects of Drugs annual 4.” Amsterdam, Oxford, Princeton: Excerpta Medica, 1980.)

The Amsterdam press, in the meantime, got a hold of van der Kroef’s report and publicized his findings. “Conclusions intended for the modest nine-point type (“’…a highly toxic hypnotic, which can rapidly induce major psychiatric disorders…’”) were magnified into headlines,” said Dukes, creating a phenomenal response from the public, which resulted in an accumulation of over 1,000 adverse reaction reports within the following weeks.
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The current promoters of triazolam as the perfect dental sedation drug, love to repeatedly characterize this kind of publicity in the “lay press” as being responsible for almost all reports of serious adverse effects, along with “junk science” and something the victim did to cause the problem coming in second and third. Never, in the triazolam supporters’ advertisements ( and they are just that, more than they are honest scientific study or discourse), is there any honest admission of the severity and frequency of the reported and well-studied adverse effects of this drug.

They fail to point out that the U.S. got a huge amount of serious adverse reports as well, many more than they got for other benzo drugs and before any bad publicity appeared in the American press. But these promoters fail to point out a lot of facts about this drug – and they consistently and repeatedly distort any “evidence” of safety. Specific examples of this assertion will follow below, but first back to the chronology.

The symptoms van der Kroef reported were soon published in Britain’s Lancet (September 8, 1979), They were quite unique in their number and bizarre quality and are as follows, as the Lancet reported them:

Severe malaise
Depersonalisation
Derealisation
Paranoid reactions
Acute and chronic Anxiety
Continuous fear of going insane
Depression and Deterioration of existing depressions
Hyperaesthesia, especially for sound, but also for smell, taste and light
Sometimes hypoaesthesia for he same stimuli
Nightmares
Restlessness
Inability to concentrate
Verbal and Physical aggression
Conflicts with entourage
Severe suicidal tnedencies
Hypnagogic hallucinations
Impulse actions
Amnaesia
Dysphagia, accompanied by nasty taste
Painful tongue and mucous membranes
Dry mouth
Loathing of food
Rigid feeling in the throat and emaciation up to 2 ½ stone (28 lbs)
Cervical pains
Headaches that are often extremely sensitive to sound
Pressure on the ears
Numb and cold feeling in fingers and toes, extending to the distal parts of the extremities
Tingling feeling
Muscular cramps and paralyses, often at the sinistral side
Catonically impaired motor functioning
Reading complaints and blurred vision
Dysfunctonal speaking and writing
Sweating

Van der Kroef added that the symptoms usually (apparently not always), “…disappear within a couple of days after stopping triazolam; sometimes there are withdrawal symptoms, such as rapidly mounting panic and heavy sweating.” He also pointed out that the side effects he listed “…appear in patients who are takng other drugs and in those who are not and in patients who have never had psychiatric treatment as well as in those with a psychiatric history. Patients with this syndrome, “ he added, “may be admitted on suspicion of brain tumour or schizophrenia. They impress the observer as seriously ill and the patients themselves often feel desperate and have to fight an almost irresistible impulse to commit suicide. I know of one patient who did commit suicide.”

Van der Kroef’s letter to the Lancet ended by saying “The Netherlands Centre for Monitoring of Adverse reactions to durgs has received several reports of patients with similar features while on triazolam and the centre issued (July 16) a letter to Dutch doctors, dealing with this matter.”

The importance of van der Kroef’s observations should not be taken lightly. It was later conceded by the U.S. and other countries that it was the 1 mg and even .5mg and higher doses that were the cause of these types of problems (if they conceded their existence at all), and that lowering the dose would settle any concerns.

The 1 mg dose, however, seems to be the most popular now among dentists, whom several admitted privately on a dentaltown forum, which I copied as evidence, that they want their patients knocked out or asleep, making it very clear that they were opposed to the ADA or anyone else restricting their ability to use triazolam and use it any way they wished to use it. After all, some of them reasoned, there’s a reversal agent, Flumazenil, that will take care of any over-dosing problems. They “reason” this, not even considering the serious dangers of the drug to some people at ANY DOSE, the more likely possibility of serious side effects at the doses they are using, and the risk of seizures caused by Flumazenil. One dentist from Alaska openly claimed to use Flumazenil on his patients whether they needed it or not. Flumazenil, he explained, has a very short shelf-life, therefore he’d “rather use it on his patients than throw it out.” I reported him to the Alaska dental board, saying that I wanted to know the outcome of their investigation. I haven’t heard a word yet.

But, I’m getting ahead of the story again.

Regardless of all the complaints it received after van der Kroef’s report, the Netherlands’ CEM didn’t seem to want to ban the drug altogether and instead offered Upjohn the opportunity to reduce the dose to a maximum of .25 mg. But Upjohn didn’t want to take the cut in its profits and refused the deal. So The Netherlands banned the drug, at least for a while.

Even though Britain felt the report was not too relevant to their own public health situation, (Britain had approved no more that .25 mg , while The Netherlands had allowed up to 1 mg), it did want and ask for Upjohn’s reassurance that the drug was safe and effective at the doses it was marketing in the UK.

Upjohn was certainly worried about all of this, and acccording to former PR manager Bruce Berger and others, it went into serious damage-control mode immediately.

Beginning with van der Kroef, who had not, nor had he intended to publish a study – he was merely doing his duty by reporting observed adverse effects – Upjohn began the discredit game: Van der Kroef’s observations were “anecdotal.” His patients had “psychiatric” problems in the first place. He didn’t accurately report the dose-effect relationship, they said, and on and on.

As Dukes put it, “Before…one subjects Dr. van der Kroef to criticism such as this, it is prudent to realize that very little adverse reaction reporting is indeed entirely watertight; go back into the history of practolol, thalidomide, or clioquinol and you will find that the initial clues which led to the identification of some drug-induced dramas were distilled from fragmentary impressions and vague suspicions in comparison with which the triazolam paper is a monument of well-documented observation.”

Furthermore, Upjohn’s criticisms of van der Kroef and his report are more than hypocritical when viewed in the light of what would be revealed in the decades to come.

Enter University of Edinburgh’s Dr. Ian Oswald, so respected in his field of study, sleep therapy, that Upjohn had initially sought him out to be on the Upjohn team (Steve Reed, Houston Chronicle). After Halcion came on the UK market, Oswald, like van der Kroef, was naturally inclined to give his patients the opporunity to benefit from the drug’s sleep-inducing quality – which no one denies is evident – at least for a brief initial period. But he, too, began noticing serious adverse effects. He told me by phone in January this year that it made some of his patients “permanently psychotic.” Oswald, along with Kirsten Adams, conducted his own studies of the drug, which found overall, as he noted in a letter to the British Journal of Medicine in 1993, that Halcion “…caused anxiety, panics, depression, paranoid reactions, and weight loss in 40 subjects compared with 40 who received pacebo and 40 who received lormetazepam,” another benzo.

In the letter Oswald added that: “No refereed publication describing research that has repeated the conditions of our research—the design, dose used, subjects averaging mid-50s in age, a trial of over two weeks’ duration—has failed to come to conclusions like our own, except a paper by Bliwise et al. Bliwise et al studied only seven subjects and the power of the design was only 0-26, which means that, as Raskin (of Upjohn) has testified, this research sponsored by Upjohn was three times more likely to miss the truth than to find it.” Oswald also pointed out that his research results “…were confirmed by the Food and Drug Administration’s analysis in 1992 of the unpublished results of Upjohn’s own research on triazolam.”

The reason Oswald knew about Raskin’s testimony, by the way, was because he had been previously retained as an expert witness in a case against Upjohn brought by Ilo Grundberg and her daughter, Janice Gray. In 1987 Grundberg had been taking Halcion for about a year when the dosage was raised to .5 mg. One night after taking the drug, she shot her elderly mother in the head eight times, killing her. After being acquitted of murder charges, based on evidence that she had been under the influence of Halcion when she shot her mother, Grundberg and her daughter sought compensation from Upjohn because of its failure to warn consumers of the risks of psychiatric effects.

In preparation for his testimony, Oswald asked to see raw data on Upjohn’s premarket trials. In one of these, called Protocol 321 (P321), Oswald discovered significant “errors” in the recording of psychiatric symptoms, reported by previously healthy subjects taking the drug. The discovery significantly altered the reported safety of the drug and brought under scrutiny Upjohn’s ethics. As soon as Upjohn became aware that this evidence would be made public if the trial proceeded, it settled and sealed all evidence from public scrutiny.

Oswald, however, didn’t shut up about it. He instead told the NY Times that Upjohn’s entire premarket process had been a fraud. Upjohn, whom internal memos later revealed was looking for a public fight, chose Oswald as its target, first calling his methods “junk science,” and then suing him for slander. Oswald countersued for the “junk science” remark, and the juryless trial took place in London in 1994. Though Judge May couldn’t or wouldn’t flat-out conclude that what Upjohn characterized as “transcription errors” was intentional fraud, he did say the company had employed “cutthroat” tactics in its PR campaign for Halcion. And the trial served to publicize the facts if not the fraud regarding it’s premarket trials of the drug. As University of Sussex researcher John Abraham later documented, only a very few of the 5000 subjects Upjohn claimed took the drug, actually took it more than a couple of days. Furthermore, many dropped out early because they could not take the serious side effects.

And there were more problems with Upjohn’s studies that the UK didn’t even know about at the time they’d asked Upjohn to reassure them of Halcion’s safety and effectiveness. One trial, conducted by Dr —- in Mississippi, had been disqualified by the FDA in 198-, because the __ had not even given the drug to anyone participating in the study. Upjohn, presenting this very study’s “results” as “evidence” for Halcion’s suitability as a sleeping pill to the UK’s CSM, didn’t bother to point out that “minor” detail – that it indeed was a total fraud.

And though the FDA did NOT disqualify all the questionable studies of another of Upjohn’s paid investigators, it was revealed in a 1994 Houston Chronicle report by Steve Reed that Dr. Fabre had recruited recovering alcoholics as subjects for his studies, this fact substantiated by an internal Upjohn memo statement, quoted by Reed.

As part of its damage control PR, responding to the van der Kroef threat, Upjohn had handsomely paid a few top scientists to meet in Boston with company officers with the goal of helping Upjohn dispell any “myths” about dangers associated with Halcion’s use. Upjohn did not tell this group about the “transcription errors” in their P321 trials report. Led by the father of psychiatric drug therapy, Frank Ayd, they all signed a letter published in the Lancet soon after van der Kroef’s appeared, backing Upjohn and Halcion’s safety. Ayd, however, later recanted saying he never would have signed it had he known of the “errors” at the time. But P321’s revelations didn’t stop at least one of these Upjohn “stooges,” David Greenblatt, currently a prestigious researcher with Tufts university, from leading a “study,” apparently on Upjohn’s behalf, presenting itself as an evaluation of the 45 “clinical trials” conducted by Upjohn in the pre-market phase of the drug’s development. Dr. Fabre’s so-called studies are among those included in Greenblatt’s evaluation, which concludes in its summary, that out of over 3000 subjects taking Halcion, “serious adverse effects were not reported.”

Greenblatt’s “evaluation” is notable for a number of reasons. Despite the fact that it is so flawed as to make it of little more use than an advertisement for Halcion, it nevertheless served to help superficially substantiate the drug’s safety as far as the FDA and the Institute of Medicine were concerned, and, more recently, with the drug’s plummeting popularity as a sleeping pill, Greenblatt’s ”evaluation” was cited by NIH”s Raymond Dionne and Charles Berthold in their own JADA published paper, which pretty much kicked off and cinched the “safety” of triazolam for use as a dental sedative. Dionne quotes only what Greenblatt exposes in his summary, failing to point out the conditions of that conclusion asserting the absence of any serious side effects. What Greenblatt admits later in his paper, but leaves out of the summary, is that ONLY one effect per subject was reported, and it was only the first effect mentioned.

Since the first effect nearly everyone experiences after taking a sleeping pill is either drowsiness, dizziness, relaxation, or decreased motor control (all CNS effects), these are the effects that got reported. Halcion’s now well-known rebound and psychiatric effects were left unreported, since they were not the first effects experienced and were the type of effects that always appeared the next day or days after taking the sleeping pill. The entire premise of Greenblatt’s evaluation was not only flawed; it was fraud – true “junk science.”

And yet Greenblatt had the unmitigated gall, just a couple of weeks ago to write me in an email that any reports of serious adverse effects related to triazolam “reflected junk science.” Along with this absurd lie, he attached a file of that 1984 evaluation of his, to substantiate his claim, I assume, apparently thinking I was as stupid as those who cite it as evidence of safety or that I was as corrupt as he is. I wrote him back to ask if this evaluation included those studies that had been shown to be either seriously flawed or full of “errors.” And I also asked him, concerning the statement in his summary – “not reported by whom, the subjects, the investigator, or you?”

He responded that he had nothing more to say about that study. I guess not.

But I’m getting way ahead of the story now.
Despite all of Upjohn’s efforts and money, the UK wasn’t buying what it was selling and banned the drug in 1991, even before Oswald’s trial publicly exposed damning Upjohn memos regarding the incident. As Claire Dyer reported in the British Medical Journal’s March 12, 1994 edition, during that trial “A 1991 memo from a junior executive on an in-house inquiry into protocol 321 was read out to Upjohn’s acting chief executive, Ley Smith, by Oswald’s counsel, Geoffrey Shaw QC. It reads: ‘There are some real concerns because of some manipulation of data by one of our people and . . . the involvement of this individual in other product submission.’ Smith replied: ‘I think manipulation of data is a bad choice of words’.” Again, I guess so.
According to Abraham, the UK’s ____ noted the following problems with the drug:

And in the end, the UK said it never would have approved the drug in the first place, had it known true results of P321.

Back in the U.S. however, Paul Leber, Halcion’s defender, especially since he was mostly responsible for it’s being on the market in the first place. Despite serious concerns expressed by other FDA medical staff, he had resisted efforts to have the drug banned in America. Comparing the two countries’ regulatory processes, Abraham and Sheppard explain a decade later that, in the UK, the one who approves the drug is not the one in charge of its on-going regulation, while in the U.S. the same person plays both roles of approver and regulator, creating a kind of conflict of interest in the sense that in the US the person responsible for removing a dangerous drug would, in a way, put into question his own decision to market it in the first place. But Abraham and Sheppard, well aware of what happened to Oswald, and being Brits themselves and not covered by US freedom of speech rights, tread very lightly on this subject, pointing out clearly, within their paper, that they weren’t pointing any fingers.

I, however, am not a Brit, and furthermore, after what triazolam has done to me and my daughter, I have nothing for anyone to sue over. So I intend to speak my mind, and I suggest there is far more to Leber’s actions than simply a concern over his reputation.
I suggest and court memos regarding his handling of Prozac support, that Leber consistently acted as more of a friend to the pharmaceutical industry than as a protector of American public health. Memos from Eli Lilly______ regarding a Prozac case, clearly show Leber’s questionable integrity in his response to premarket trials showing high numbers of suicides associated with the drug’s use. Specifically Leber

So, in the U.S. life or death by Halcion came down to Paul Leber, who now works for the phamaceutical industry. Ultimately the FDA, whose JOB it is to protect “…the public health by assuring the safety, efficacy, and security of human and veterinary drugs…” (see FDA website), is responsible for destroying my daughter’s life and killing John Coleman and others.
So what is our recourse. Just sit here and take it – spend hours of what’s left of our lives trying to get a lawyer to take our case – searching and pleading even to get a malpractice case filed against the dentist – the fall guy in the whole scenario? And even if we find someone to go after the little guy, what lawyer in America has enough money or the agility with a slingshot to take on the FDA?
Even before the drug came on the US market, one of FDA’s doctors, Teresa Wu, had serious reservations about allowing it. Then after it did, she expressed more serious concerns about all the adverse reactions being reported. In 1987, Edward O. Bixler at Penn State’s Sleep Research and Treatment Center reported findings from a comparison of rates of reported adverse drug reactions among patients taking flurazepam, temazepam, and triazolam (all benzos), based on data collected thorugh the FDA’s spontaneious reporting system. The rates “…were controlled for the number and size of new prescriptions for each drug.” Bixler noted that “Hyperexcitability and withdrawal effects were greatest for tirazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates of other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs.”
Interestingly Bixler, who would soon, along with other honest doctors, call for a banning of the drug, conducted studies now being cited as evidence of triazolam’s suitability and safety as a dental sedative, one reason being that the dental industry is promoting the amnesia effect as an asset – it’ll make you forget you had a dental procedure – failing to point out that the amnesia associated with triazolam has been known to make a person forget what they did for hours following one dose.
. And it wasn’t only the general public reporting these reactions. As early as 1985, Q.R. Regestein and P. Reich published a paper in the Journal of Clinical Psychiatry (46:280-3), showing problems in six patients treated for insomnia with triazolam, beginning at .5 mg. “Although this treatment effectively controlled the patients’ insomnia,” the authors noted, “all patients experienced an increased level of anger and agitation.” One patient “developed visual hallucinations,” and another “…had three incidents of bizarre behavior.”
However, it wasn’t reported until September, 1989, that the FDA was “…looking into a ‘relatively high’ number of reports about unwanted side effects from the drug Halcion, the world’s most widely prescribed sleep medication,” an Orlando Sentinel report said, adding that the FDA would review reports “…to determine why more adverse reactions have been reported for Halcion, made by The Upjohn Co., than for other such drugs.” The article added that spokesmen at the FDA “…were unable to say what the reported symptoms are.”
Obviously, the FDA didn’t want to admit how dangerous and serious they were, because certainly they were able to disclose the information Bixler had already reported. The Orlando paper, however, didn’t let them get away with this attempt at secrecy, adding that “…when Halcion was approved, the agency was aware of a variety of adverse effects including confusion, agitation, hallucinations, amnesia and bizarre behavior.”
And if there’s one word one would choose to characterize my daughter’s behavior since she was overdosed with triazolam, that word would most definitely be “bizarre.”
A day after this report was published in the Orlando Sentinel, another followed, saying the agency’s advisory committee had “…recommended a stronger warning to doctors on the possibility of amnesia in patients taking …Halcion…. The panel also recommended that the FDA prepare an informaton packet that doctors can give their patients that take sleeping pills of the same class as Halcion.” So here you see how the spin works. They admit only to amnesia and then try to make it appear that Halcion is just like others in its class – a far cry from the actual results of that FDA comparison as Bixler had summarized it, and as it actually was.
By this time Ilo Grundberg in Utah had already been acquitted of killing her mother, while under the drug’s influence, and she and her daughter had initiated a lawsuit against Upjohn for 21 million for not warning the public of these deadly risks. So in light of these deadly risks, FDA’s “possibility of amnesia” warning in 1989 looks even more ridiculous.

Tags: Corruption of FDA documented, exposed, Part I, Triazolam story