According to Mr Finkelstein, the evaluation of serious adverse events during the original clinical trials showed the risk of suicide was known and a major concern. In the letter to Dr Katz, he pointed out that an FDA reviewer specifically stated in December, 1992:
Serious adverse events may limit the drug's widespread usefulness. Depression, while it may not be an infrequent occurrence in the epileptic population, may become worse and require intervention or lead to suicide, as it has resulted in some suicidal attempts during clinical trials.
In fact, in the clinical trials, Neurontin was attributed to four people actually attempting suicide, two more having depression with suicidal ideations, and 22 participants reporting depression so severe it required pharmacologic intervention. Most alarming was that 19 of the 78 participants who reported depression had no prior history of depression.
"Clearly," Mr Finkelstein told Mr Katz, "the FDA did not approve this drug with any expectation of use beyond the approved indication."
Documents that surfaced in litigation also show that the FDA was aware of the off-label marketing scheme eight years before the DOJ settlement. In July, 1996, FDA official, Lesley Frank, wrote to Parke-Davis and said in part:
Parke-Davis may be promoting Neurontin for 'off-label' uses ... in printed promotional materials, in detail or sales presentations to physicians, and through the use of company-solicited physician participation in a series of teleconferences.
These promotions of Neurontin for off-label uses included, but were not limited to, its use in chronic pain, bipolar disorders, and other psychiatric conditions. As you are aware, Neurontin's only approved indication was for adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy.
The documents show that after 11 months, Parke-Davis sent a written response denying all the allegations and the FDA accepted the denials and the matter was dropped.
In reality, $430 million was chickenfeed to Pfizer, considering that at the time of the settlement, Neurontin sales were up 32% from 2003, and the 2004 sales were expected to exceed the $2.7 billion mark set in 2003. In actuality, the settlement amounted to only about 15% of the gross sales of Neurontin in 2003.
By 2002, a full 94% of Neurontin sales were for off-label use and according to the August 16, 2004, USA Today, when Pfizer settled the lawsuit, the Wall Street firm Lehman Bros estimated that 90% of the sales were still off-label.
At the time, Pfizer issued a statement that said the illegal practices took place before Pfizer acquired Warner-Lambert. However, sales figures clearly show that Pfizer was still reaping the benefits of the illegal promotion of Neurontin at the time of the settlement.
"Although Neurontin is prescribed for scores of off-label indications," Attorney Braslow reports, "since 2000 off-label use continues to be most common in the areas where the company focused its illegal marketing efforts such as bipolar disorder, peripheral neuropathy and migraine headaches."
"This increase," he points out, "is most likely a direct result of sales representatives and leading physicians, who were paid by the company recommending its use for these conditions."
According to Attorney Pogust, "there are no scientific studies that support Neurontin's use for pain disorders."
"But as a result of the company's previous promotional activities," he says, "tens of thousands of patients who could use other pain killing drugs whose effectiveness has been established, are given Neurontin."
"These prescriptions for pain," Mr Pogust notes, "are still being written, as a direct result of past illegal promotional activities."
Psychotherapy and especially alcohol also up suicide risk?
There is evidence (Bridge JA, et al, 2005) that cognitive and behavioral therapies also increase suicide risk to about the same level as prescription drugs.
I look forward to Ms Pringle's articles on this little psychotherapy secret.
And let us not forget that alcohol is involved in 30-50% of completed suicides (in some eastern European countries it is as high as 90%). Yet breweries and distilleries are not required to put black-box warnings on their products. It is time this scandal was exposed.
by
slothman (0 articles, 0 quicklinks, 0 diaries, 1 comments)
on Tuesday, February 20, 2007 at 6:14:40 PM
