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This might help with regard to causation AND as to the question of suicide figures:

(Please bear in mind when trying to work the following out, that many studies were done EXCLUDING people who were (or had been) suicidal to try to avoid suicides negatively affecting clinical studies, and that in some studies perfectly healthy volunteers also became suicidal and some actually committed suicide, and that many trial participants were said ("coded") to have dropped out because of "nausea" but who actually dropped out because of suicidal acts).

1) From correspondence between a psychopharmacological expert to a regulatory agency:

"...Reports on these trials list patients who have committed suicide, and list those patients as being of a certain age and as having committed suicide at a certain point during the trial, when the patient in question has a very different age and the event in question happened at a completely different point during the trial".

"Miscoding of suicidal act as emotional lability."

" Lilly have resorted to treatment non-response and a range of other headings to code what happened." [re coding/mislabelling suicidal acts happening on clinical trials]

"...records on Prozac, Seroxat/Paxil and Lustral/Zoloft, you will find cases of homicidality coded as nausea for instance."

"Discontinuation of patients from studies for primary adverse effects such as nausea when in fact there has been a suicidal act;"

"But it is also worth adding specifically that this has been a feature of all trials of Zoloft/Lustral, Seroxat/Paxil and Prozac throughout, as far as I can make out... "

2) AMERICA'S LOST DREAM: Life, Liberty and the Pursuit of Happiness
By James W. Prescott, Ph.D.
(http://www.violence.de/prescott/appp/ald.pdf)

V. Depression and Suicide in Children and Youth of America
Depression and suicide are of epidemic proportions in America. Suicide has been the third leading cause of death in the youth age group of 15-24 years for the past generation (1979-1997) and is the fifth and sixth leading cause of death in the 5-14 year age group for the years 1979 and 1997, respectively. Tables 2 & 3 show that the suicide rates have doubled in the 5-14 year age group from 1979-1997. Table 4 gives the number of suicidal and homicidal deaths for the years 1979, 1994 and 1998 for the age groups of 1-4 years; 5-14 years and 15-24 years. The total number of suicidal deaths in these age groups for the years 1979, 1994 and 1998 are 5,398; 5,274 and 4,321, respectively. This represents an average of 4,999 suicide deaths per year for these years.

Given the average of 5,000 suicidal deaths per year, the estimated total number of suicidal deaths in these age groups from 1979-2000 is 105,000 children and youth who have committed suicide over this past generation. More children and youth (ages 5-24 years) have committed suicide in the past ten years than the total number of American combat lives lost in the ten year Vietnam War (est. 55,000 v 47,355), yet little or no public attention has been given to this reality and what it represents.

There are an estimated 60,828 suicides in the 25-44 year age group for the five years from 1994-1998 (12,166x5=60,828), an estimated total of 121,656 American lives lost to suicide for ten years in this age group that is more than double all the American lives lost in the ten year Vietnam War.

Table 5 gives the suicide rates as a percent of the homicide rates for these specific age groups and for the years 1979, 1994 and 1998. For the 5-14 year old age group, suicide rates, as a percent of homicide rates, have systematically increased from 1979 to 1998, as follows: 1979:36%; 1994: 60 %; 1998:73 %.

Suicidal death, relative to homicidal death, has dramatically increased for our children and youth in the 5- 14 year age group from 1979-1998. The question that remains unanswered is why do our children and youth prefer suicidal death to living in America, presumably the healthiest, wealthiest, and greatest nation of the world? Clearly, these dramatic increases in suicide rates over a single generation cannot be attributed to any changes in the human gene pool.

These statistics indicate that America is an unsafe nation to rear its children and this conclusion is also supported by the epidemic of depression that afflicts our children and youth, as evidenced by their massive psychiatric medication (Zito, et.al, 2000). Some 1.5 million prescriptions of the anti-depressant class of drugs called the serotonin re-uptake inhibitors (SRIs, e.g., Prozac) are given annually to children and youth and some 3 million prescriptions of Ritalin are prescribed annually. The problem of underestimating child/youth suicides in our society is as real as it is for child abuse homicides, previously cited (Herman-Giddens, et.al, 1999), where they found that child abuse homicides were underascertained by 62%. It is reasonable to project a similar or larger underestimation of suicidal deaths, given the higher societal and family shame and guilt that is associated with suicidal death, particularly of children and youth. Undoubtedly, many suicidal deaths are hidden in the accidental death statistics and are a greater problem than the current statistics indicate.

The pioneering study of Salk, et al (1985) found prenatal and perinatal stress factors in 81% of teen suicides that represented a 400% increased risk of suicide compared to the control subjects. The studies of the Jacobson group in Sweden also documented the role of perinatal trauma and obstetric medications on later adult behaviors of suicide, homicide and drug addictive behaviors, where increased risks for some of these behaviors was as high as 500% compared to control groups (Jacobson, et al, 1987,1988, 1990, 1998/ 2000). The study of Raine, et al (1994) found birth complications and maternal rejection predicting violent crime at 18 years of age, which adds additional evidence that prenatal/perinatal trauma contributes to adult behavioral disorders. The report of Levy (1945) that the trauma of circumcision can lead to homicidal and suicidal emotional states should not be neglected in the overall assessment of prenatal, perinatal and postnatal factors that contribute to child, teen and adult emotional-behavioral disorders.

VI. Psychiatric Medications of the Children and Youth of America.
Breggin (1994, 1995, 1998) has warned America about the effects of a Toxic Psychiatry upon the children and youth of America, which have gone unheeded. The psychiatric drugging of the children, youth and adults of America have become worse where there is little or no questions being asked by the psychiatric-political establishment as to why are all these psychiatric drugs are necessary. Breggin (2000) provides a framework for the prevention of the psychiatric drugging of the children and youth of America and a path to follow, if natural happiness is to become a reality, which is the true prevention of depression and violence.

Zito, et al (2000) have reviewed the prevalence of psychotropic medication use in children and youth; and in preschool-aged children from 1991-1995 from two state Medicaid programs and an HMO. They reported: The prevalence of psychotropic medication treatment for children and adolescents with emotional and behavioral disorders has significantly increased in the United States during the last few decades, particularly in the last 15 years. Specifically the 5 through 14-yearold age group has experienced a great increase in stimulant treatment for attention-deficit/hyperactivity disorder (ADHS), and the 15 through 19 -year- old age group has had sizable increases in the use of antidepressant medications (pp.1-2)... The rate of psychotropic medication prescribed for preschoolers in the MWM program increased substantially from 1991-1995. The increase was greatest for clonidine (28.2-fold), stimulants (3.0-fold), and antidepressants (2.2-fold). By contrast, neuroleptic use did not increase substantially during this time (p.4)... Methylphenidate (Ritalin) use according to age group in children and adolescents in the MWM program was most prominent for those aged 5-14 years... The largest methylphenidate increase (311%) was among 15 through19- year olds, whereas the 2 through 4- year-olds, like the 5-through 14 -year-olds, had a smaller but still substantial increase (169% to 176%) (pp.4-5)...

Several prominent trends characterized the use of psychotropic medications in preschoolers during the early to mid 1990s. Overall, there were large increases for all study medications (except the neuroleptics) and considerable variation according to gender, age, geographic region, and health care system. These findings are remarkable in light of the limited knowledge base that underlies psychotropic medication use in very young children. Controlled clinical studies to evaluate the efficacy and safety of psychotropic medications for preschoolers are rare. Efficacy data are essentially lacking for clonidine and the SSRIs and methylphenidate's adverse effects for preschool children are more pronounced than for older youths. Consequently, the vast majority of psychotropic medications prescribed for preschoolers are being used offlabel. (P.5).

Recall that this 5-14 year age group showed a doubling of suicide rates over the past twenty years (supra).

3) Lilly internal document

"Activation and sedation in fluoxetine clinical trials,"

http://i.cnn.net/cnn/2005/images/01/03/eli.lilly.pdf
Adobe acrobat reader required.

Amongst other very informative information in the document about 'activation' of agitation etc, on PAGE 3 of the document you'll see far higher suicidality figures with Prozac than with 4 'pre-SSRI' drugs its compared with under the heading:

"Percent of Total Reports (SUICIDALITY All Events) For Each Drug"

FLUOXETINE (Prozac) 3.7
Trazadone 0.2
Amitriptyline 0.8
Desipramine 0.3
Maprotiline 0.0

4) http://www.ahrp.org/risks/usSSRIuse0604.pdf

(PDF file, Acrobat Reader required).

On just 3 SSRIs: PROZAC, PAXIL (Seroxat) and ZOLOFT (Lustral) in one year alone:

"...Table 1 shows that, in 2002, 7.8 million Americans became new users of either Paxil,Prozac or Zoloft and therefore they faced a net risk of induced suicide that is not likely to be lower than 32/100K and very probably is higher than 104/100K.

Nevertheless, even using these cautionary rates, somewhere between 2500 and 8200 **excess** suicides may have occurred in 2002 alone due to these drugs..."

WITH REGARD TO THE PDF FILE under 3) (now confirmed by Eli Lilly that it IS there document)

The 1988 document indicated that 3.7 percent of patients attempted suicide while on the blockbuster drug, a rate more than 12 times that cited for any of four other commonly used antidepressants.

The document, which cited clinical trials of 14,198 patients on fluoxetine -- the generic name for Prozac -- also stated that 2.3 percent of users suffered psychotic depression while on the drug, more than double the next-highest rate of patients using another antidepressant.

In addition, the paper said that 1.6 percent of patients reported incidents of hostility -- more than double the rate reported by patients on any of four other commonly used antidepressants.

The trials reviewed in the document said that 0.8 percent of users of Prozac reported causing an intentional injury -- eight times the rate associated with any of the other antidepressants.

In the paper, titled "Activation and sedation in fluoxetine clinical trials," the authors said that the drug may produce nervousness, anxiety, agitation or insomnia in 19 percent of patients, and sedation in 13 percent of patients.

The paper, apparently produced by the drug company's marketing department, said "several suggestions may be helpful in presenting this information to physicians," including emphasizing that more patients on another class of antidepressants stopped taking their drugs than did those on Prozac..."

(Zoloft is in the same class - SSRIs - carrying the same side effects as Prozac.)

"...The 1988 document indicated that 3.7 percent of patients attempted suicide while on the blockbuster drug, a rate more than 12 times that cited for any of four other commonly used antidepressants.

The document, which cited clinical trials of 14,198 patients on fluoxetine -- the generic name for Prozac -- also stated that 2.3 percent of users suffered psychotic depression while on the drug, more than double the next-highest rate of patients using another antidepressant.

In addition, the paper said that 1.6 percent of patients reported incidents of hostility -- more than double the rate reported by patients on any of four other commonly used antidepressants.

The trials reviewed in the document said that 0.8 percent of users of Prozac reported causing an intentional injury -- eight times the rate associated with any of the other antidepressants.

In the paper, titled "Activation and sedation in fluoxetine clinical trials," the authors said that the drug may produce nervousness, anxiety, agitation or insomnia in 19 percent of patients, and sedation in 13 percent of patients.

The paper, apparently produced by the drug company's marketing department, said "several suggestions may be helpful in presenting this information to physicians," including emphasizing that more patients on another class of antidepressants stopped taking their drugs than did those on Prozac.

The 1988 document indicated that 3.7 percent of patients attempted suicide while on the blockbuster drug, a rate more than 12 times that cited for any of four other commonly used antidepressants.

The document, which cited clinical trials of 14,198 patients on fluoxetine -- the generic name for Prozac -- also stated that 2.3 percent of users suffered psychotic depression while on the drug, more than double the next-highest rate of patients using another antidepressant.

In addition, the paper said that 1.6 percent of patients reported incidents of hostility -- more than double the rate reported by patients on any of four other commonly used antidepressants.

The trials reviewed in the document said that 0.8 percent of users of Prozac reported causing an intentional injury -- eight times the rate associated with any of the other antidepressants.

In the paper, titled "Activation and sedation in fluoxetine clinical trials," the authors said that the drug may produce nervousness, anxiety, agitation or insomnia in 19 percent of patients, and sedation in 13 percent of patients.

The paper, apparently produced by the drug company's marketing department, said "several suggestions may be helpful in presenting this information to physicians," including emphasizing that more patients on another class of antidepressants stopped taking their drugs than did those on Prozac..."

In the paper, titled "Activation and sedation in fluoxetine clinical trials," the authors said that the drug may produce nervousness, anxiety, agitation or insomnia in 19 percent of patients, and sedation in 13 percent of patients.

Actually it turned out to be twice that, 38%. The wonders of statistics!! Neverdem posted it here. It is good article that touches on some of the "methods" used.

January 17, 2005
Dispute Puts a Medical Journal Under Fire
By BARRY MEIER

Last year was an especially bad one for the pharmaceutical industry, which experienced controversies over how drug studies are disclosed and the implosion of the painkiller Vioxx. Now, as a result of the recent publication of an article about the antidepressant Prozac, it appears that the staid, usually methodical world of medical journals could suffer its own black eye.

On New Year's Day, the British medical journal BMJ published a news article suggesting that "missing" documents from a decade-old lawsuit indicated that Eli Lilly & Company, the maker of Prozac, had minimized data about the drug's risks of causing suicidal or violent behavior.

Within days, the article was cited in hundreds of television and newspaper reports. An outraged Washington lawmaker demanded to know if Lilly had hidden the information from the Food and Drug Administration. While company officials refuted the article's assertions, it was still repeatedly cited. And last Thursday, Lilly spent about $800,000 to run full-page advertisements in 15 major publications to dispute the article.

The incident may prove to be a messy one for the BMJ, which is based in London and owned by the British Medical Association, a professional group. Much of the journal, formerly known as the British Medical Journal, is devoted to research reports about medical issues that are reviewed by experts. But the BMJ, like some other medical journals, also has a separate news section that prints articles like the recent one about Prozac. As it turns out, some of the Eli Lilly documents, which the BMJ said it received from an anonymous source, have been circulating for years. And, Lilly officials said, the BMJ and its reporter declined to provide the company with copies of the documents at issue prior to the article's publication.

The American freelance reporter who wrote the article, Jeanne Lenzer, declined to be interviewed, referring all questions to the BMJ. Officials there did not respond to written questions, but a spokeswoman, Emma Dickinson, said in an e-mail message on Friday that the publication "takes this issue very seriously" and will address Lilly's concerns after reviewing them.

The BMJ, which is considered a leading medical journal, may have little choice. While Lilly has not taken legal action, its lawyers have notified the publication that the company considers the article to be "inaccurate and defamatory," asserting that the records were not missing and that all their relevant data had been previously submitted to the F.D.A. Also, Lilly issued an analysis last week of the 52 pages of records that the BMJ had received, which the company said supported its claims. Lilly said it got the documents from a congressman who received them from the BMJ.

"You put something out on the newswire with the imprimatur of a medical journal and people think it is fact," said Dr. Alan Brier, the chief medical officer of Eli Lilly, which is based in Indianapolis.

The article's appearance follows the recent controversy over whether drug makers adequately disclosed the risks that antidepressants like Prozac posed to pediatric patients. And its comes as a South Carolina teenager faces trial for murder as an adult on charges that he killed his grandparents when he was 12. The teenager, Christopher Pittman, has acknowledged the crime, but his lawyers have based his defense on the argument that he became violent after taking the drug Zoloft, an antidepressant similar to Prozac.

It was in a little-noticed article written by Ms. Lenzer in the Dec. 11 issue of the BMJ about the Pittman case that she first mentioned that the publication had received "a set of documents that mysteriously went missing from a U.S. mass murder case ten years ago."

That article did not go into specifics. But in her article on Jan. 1, Ms. Lenzer wrote that the documents in question were connected to a Prozac-related lawsuit that grew out of a shooting rampage in 1989 by a Kentucky man, Joseph Wesbecker, that left nine people dead, including Mr. Wesbecker.

Lawyers representing the victims sued Lilly, asserting that Mr. Wesbecker's killing spree was caused by Prozac, a drug he had been prescribed just before the crimes. During the 1994 trial of the case, Lilly pointed to Mr. Wesbecker's long history of severe psychological problems and said that Prozac was safe.

To combat those assertions, plaintiffs' lawyers introduced hundreds of Lilly documents. They argued that the records showed that Lilly had fully disclosed to the F.D.A. in the late 1980's the potential of Prozac to produce suicidal thinking or acts of violence, including all the reviews by drug regulators in Germany of the issue at that time. Lilly disputed that.

The jury found in favor of Lilly. But a legal controversy over the trial later erupted when it was revealed that plaintiff lawyers and Lilly lawyers had reached an undisclosed financial deal just before the case went to the jury to effectively settle by agreeing not to appeal the verdict.

A Lilly spokesman, Phil Belt, said that Ms. Lenzer, who lives in Kingston, N.Y., first contacted the company on Dec. 13, a few days after her article about the Pittman case appeared.

Mr. Belt said Ms. Lenzer asked where a published report about the data in a specific 1988 internal Lilly report had appeared. At that time, she also requested an interview with the company's chief executive, Sidney Taurel, to discuss what she described as "missing" Lilly documents, Mr. Belt said.

Mr. Belt said the company told Ms. Lenzer that Lilly needed to see the records at issue before it proceeded. He added that Ms. Lenzer later told Lilly that she could not do so, saying that the source of the documents was anonymous.

As the Christmas and New Year's season approached, Mr. Belt said that Ms. Lenzer told Lilly officials that they could pick up the issue after the holidays.

At some point in December, however, Ms. Lenzer or her editors apparently sent the documents it had received to Congressman Maurice Hinchey, Democrat of New York, and to the F.D.A. And a few days before New Year's, the BMJ distributed Ms. Lenzer's article to other news organizations with the provision they could not write about it until its publication date on Jan. 1 - a practice known as an "embargo."

That article carried the headline, "FDA to Review 'Missing' Drug Company Documents," which caught the attention of other news organizations. Mr. Belt said that when Lilly became aware of the embargoed news release, it tried to reach editors at BMJ but was unsuccessful. Both Ms. Lenzer and the BMJ did not respond to written questions about the publication's interactions with Lilly, including why the documents were not shown to the drug maker.

The only Lilly document specifically mentioned in the BMJ article was a 1988 report that stated that 38 percent of depressed patients taking Prozac during clinical trials experienced side effects like agitation, insomnia and nervousness, a rate twice that of those taking a placebo.

Such side effects, which are sometimes referred to as "activation," reflect the fact that some depressed patients who take Prozac and drugs like it often experience a surge of physical energy well ahead of psychological recovery. Some experts have long expressed concerns that such reactions can be so severe in a few patients that they may ultimately act on suicidal or violent impulses.

For procedural reasons, the 1988 Lilly memo itself was not introduced as evidence in the Wesbecker case, said Nancy Zettler, one of the two plaintiffs' lawyers involved. But Ms. Zettler said that one of her expert witnesses, Dr. Peter Breggin, testified extensively about its contents at that trial.

Ms. Zettler said that she was so perplexed by the BMJ article that she contacted Ms. Lenzer after it appeared. "Her original article made it seem like we had deep-sixed some of this stuff and I was curious," she said.

Both Ms. Zettler and Paul Smith, the other plaintiffs' lawyer in the Wesbecker case, said that Ms. Lenzer did not contact them prior to the article to talk about the records or ask for others from that case.

Another plaintiffs' lawyer who has used Lilly documents in other lawsuits, Arnold Vickery, also said he did not discuss the records with Ms. Lenzer prior to her report. Mr. Vickery and another lawyer are representing Christopher Pittman.

Dr. Breggin has written articles arguing against the use of Prozac and other drugs and has mentioned the 1988 Lilly memo in his writings; he is scheduled to be an expert witness in the Pittman case.

Several pages sent to the BMJ were not produced by Lilly but are photocopies of slides produced by an F.D.A. official who presented them at a 1991 public hearing that reviewed the possible suicide risks of Prozac. After its review, that agency panel decided not to issue any additional warnings.

Ms. Zettler said she still thinks the issue of what Lilly told the F.D.A. in the mid-1980's about Prozac's potential risks is unsettled. But after more than 15 years of the drug's use, numerous lawsuits and public reviews, it may also be largely moot.

As a result of the recent controversy about the potential suicide risks posed by antidepressants to children and teenagers, the F.D.A. last week sent out final new labeling language about those dangers to all makers of such drugs, including Lilly.

A spokeswoman for the agency, which is still reviewing the records sent to BMJ, said that it had not yet found anything new in them. Ms. Dickinson, the publication's spokeswoman, said that it was reviewing Lilly's rebuttal to its article.