My oncologist told me about this today when we were discussing the FDA. His words "it is totally corrupt".  I worked at the National Cancer Institute and said what he saw there between the originations what horrible to see. I read today 60% of the FDA is now funding by drug companies.

This drug was said to help neuropathy and there was zero proof!  How this got out was a Harvard intern doing a study at the FDA ran across this info and sent a whisper blower email up the change of command until some one did something.

Now many times has this happened? 

Flalady

The Food and Drug Administration has asked the makers of all epilepsy drugs to re-examine their clinical trial data in response to claims that one of the medicines, Pfizer's Neurontin, boosts the risk of suicide.

Word of the FDA action came in response to a petition filed last May by personal injury attorney Andrew Finkelstein, who has been urging the agency to warn doctors that the commonly prescribed drug Neurontin can lead to severe depression and suicide.

Neurontin, with $2.7 billion in sales last year, has been prescribed to more than 10 million people since it was put on the market in 1994. Although it was formally approved for patients suffering from epilepsy and later for pain related to a skin disorder, it has since been prescribed for illnesses ranging from psychiatric disorders to back pain.

Finkelstein bases his claims on the FDA's own records as well as 318 suicides and about 2,000 suicide attempts among families he represents.

The FDA's inquiry comes as it tries to repair its image as the guardian of drug safety after a series of controversies over its response to warnings about serious side effects linked to several other blockbuster medicines.

The probe of epilepsy drugs is similar to the FDA's examination last year of a class of widely prescribed antidepressants, including Paxil. That inquiry eventually resulted in strong warnings that antidepressants could increase suicide risks. But the case damaged the FDA's credibility when families and their lawyers accused the agency of suppressing a report by one of its own experts.

The agency came under fire again for its handling of drug safety concerns when Merck & Co. suddenly withdrew its widely sold painkiller Vioxx in September due to cardiovascular risks that experts had been urging the FDA to act on for years.

The FDA, in a letter Finkelstein shared with The Chronicle, said it is now requesting that Pfizer and 13 other manufacturers reanalyze the results of their controlled clinical trials for signs of suicidal thoughts and actions. According to the National Society for Epilepsy, there are at least 23 prescription drugs that are approved for the treatment of epilepsy. But an FDA spokeswoman said she could not supply the names of the other drugs subject to the inquiry.

Pfizer received the letter last month and said it will comply with the FDA request but denied that Neurontin increases the risk of suicide.

"Pfizer maintains an extensive program for tracking and reporting medical events associated with the use of Neurontin, as we do for all our medicines,'' said company spokesman Bryant Haskins. "The comprehensive data -- including clinical trial results -- that we've submitted to the FDA over the past decade refute any suggestion that Neurontin causes depression, suicidal thoughts or suicidal behavior.''

Finkelstein sees the FDA's response to his petition as part of a pattern of agency delays when serious potential drug risks arise. The attorney wants the FDA to include a prominent suicide warning on Neurontin's label. He also thinks it should ask an independent expert to analyze the drugmakers' data and demand disclosure of any trials the manufacturers haven't published.

In addition, he wants the agency to alert doctors that it is now investigating the possible suicide risk, to encourage heightened monitoring of Neurontin patients.

"I think they're taking modest steps when they're confronted with what could be a very significant issue,'' Finkelstein said.

A top FDA official said the agency had been looking into possible suicide links with "mood stabilizers'' like Neurontin for some time before Finkelstein's petition was filed, based on lessons the agency learned from the antidepressants case.

"We'd like to get an answer to the question: Can it make your mood worse?'' said Dr. Robert Temple, associate director for medical policy at the FDA's Center for Drug Evaluation and Research.

But Temple said the FDA will not issue advisories to doctors during the six months that the manufacturers have to review their data, unless the agency finds significant signs of a suicide danger. "So far, we have not,'' he said.

Neurontin has already been the focus of one of the recent drug company scrapes that have trained a harsh light on the industry. Neurontin is FDA- approved only for epilepsy and pain associated with a skin disorder, but it is widely prescribed for back pain, psychiatric illnesses and other conditions --

that is, so-called off-label uses not approved (but not forbidden) by the

FDA.

That huge off-label market resulted from illegal promotional tactics such as treating doctors to luxury trips, government prosecutors charged last year. They won a $430 million settlement and guilty pleas from the drug's former manufacturer, now a unit of Pfizer, which is the world's largest drug firm.

In spite of that, as well as findings by expert pharmacologists that Neurontin has little value in most off-label uses, the drug's revenues rose in 2004. So the FDA's finding on Finkelstein's safety claims could affect millions of Americans.

Finkelstein is the managing partner of a multibranch law firm based in Newburgh, a small city beside the Hudson River north of New York City. He filed his petition to the FDA after he found that 25 people taking Neurontin had committed suicide between 1998 and mid-2003, according to MedWatch, an FDA program that receives voluntary alerts from doctors and others. This "passive surveillance'' system is estimated to capture about a tenth of actual side- effect cases.

Finkelstein said his law firm then did what he thinks the FDA should be doing: It actively searched for other cases. When the firm placed ads asking if patients displayed suicidal behavior on Neurontin, it received thousands of calls. Finkelstein said he weeded out people who had ever attempted suicide before taking the drug.

Among the more than 2,300 families he represents are the Richardsons of San Jose. Lori Richardson's husband, Timothy, committed suicide in 2003 at the age of 34, leaving behind a young son and daughter. Richardson said her husband's personality changed after he started taking Neurontin in 2000 for pain from spinal fusion surgery that repaired a work injury. The tall commercial plumbing division manager -- introverted and a meticulous planner -- became agitated, aggressive and impulsive, she said.

"He knew it,'' Richardson said. "He would tell the doctors, 'I'm not like I always have been.' ''

Doctors prescribed antidepressants. Timothy Richardson also received the narcotic-based painkiller Vicodin and developed an addiction, his wife said. Financial pressures and caring for the couple's two children were other stresses, she acknowledges. But she suspects Neurontin was a crucial factor in his intentional overdose.

Finkelstein said all the suicide cases he found involved people taking Neurontin for off-label uses, with about 50 percent given it for pain-related problems like migraines or back aches. He said the FDA has not done enough to curb off-label prescribing of Neurontin, particularly for psychiatric illnesses like bipolar disorder, where depression is already a factor. The lack of a suicide warning on the drug's label is an indictment of the drug regulatory system, he said.

"It's structured to benefit sales to pharmaceutical companies rather than to provide necessary information to prescribing physicians and their patients, '' said Finkelstein.

Pfizer says Finkelstein's petition is a ploy to bolster his clients' lawsuits against the company. Haskins, the company spokesman, said the data don't support Finkelstein's demand for a prominent "black box'' warning on Neurontin's label -- the FDA's most stringent enforcement action short of banning a drug.

"It's simply irresponsible to promote the false impression that a causal link exists between the use of Neurontin and suicide,'' said Haskins.

Although suicide is not listed in the warnings section of Neurontin's FDA label, other parts of the 29-page document note that symptoms like depression, anxiety, psychosis, and a category dubbed "suicidal'' have cropped up among adults and adolescents in various clinical trials, and may be related to Neurontin.

The "suicidal'' symptom was listed as infrequent, occurring in 1 out of 100 to 1 out of 1,000 patients. At that rate, for every million patients on the drug, 1,000 to 10,000 people might experience the side effect. However, some of the studies were not placebo-controlled, so any causal effect of the drug would be hard to quantify.

Finkelstein wants the label information updated to include completed suicides. He sees further proof that Neurontin boosts suicide risks in an FDA document turned over to him in litigation against Pfizer.

In 1992, an FDA official who reviewed the marketing application submitted for Neurontin by Parke-Davis, its original manufacturer, noted that a small fraction of clinical trial participants with epilepsy became seriously depressed while on the drug, and two attempted suicide.

"Depression, while it may be not 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,'' wrote the FDA reviewer, Dr. Cynthia McCormick. That might limit the drug's usefulness, she concluded.

But McCormick, now a private consultant, said she had deferred to the judgment of much more experienced FDA reviewers who also evaluated Neurontin in 1992. The data did not prove that the drug was responsible for the suicide attempts, she now says.

"This is not an unexpected event in the population it was approved for,'' said McCormick, who did a brief consulting assignment for Pfizer about a year ago.

Finkelstein said he had offered the FDA information from his clients' case reports early last year and was flabbergasted when he was told to hire a pharmacology expert to provide the FDA with a risk analysis. That's the FDA's job, Finkelstein said, not a lawyer's.

The FDA official who responded to Finkelstein's petition in an April 12 letter said he had asked the attorney to hire an expert because the agency would have had difficulty evaluating whether Neurontin played a role in the suicides.

Other factors, like the various different medications taken by the patients, and the fact that many suffered from psychiatric illnesses that carry inherent suicide risks, would complicate the analysis, wrote Dr. Russell Katz, director of the FDA's Division of Neuropharmacological Drug Products.

Assessing drugs for suicide risks is not easy even in controlled clinical trials, Temple said. Suicides are rare enough that even a large trial might not show a significant difference between those on the drug and on a placebo.

Many of the trials the manufacturers will be reviewing were not designed to assess suicide risk, Temple said. But the FDA might find hints of a risk. In a trial of one epilepsy drug, he said, 1.1 percent of participants committed suicide versus 0.4 percent on placebo. If those hints add up, the FDA might take action, Temple said.

If Neurontin appears to boost suicide risks, the agency might advise doctors to restrict its off-label use, Temple said. But he said it's too early to predict the outcome of the epilepsy drug probe.

sweetlady2,

I'm so happy you stood up for what you believed in.  I just wish we had more doctor's who would do the same.

Flalady