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In Reply to: Re: Glad to see yours and Josephs story posted by Skep on February 18, 2006 at 22:53:42:
I think you'll find this interesting also.
PROZAC'S CLINICAL TRIALS
How did a drug with such potentially dangerous side effects make it into the marketplace? One reason is that the clinical trials for Prozac were flawed, according to documents released under the Freedom of Information Act. Consider:
* Eli Lilly told physicians involved in the trials to record a variety of adverse reactions, including suicidal ideation, morbid thoughts, agitation, sadness and insomnia, as "symptoms of depression," rather than as separate effects. In a review of Prozac, FDA Efficacy Reviewer J. Hillary Lee stated, "Note: the exhortation [by Lilly] to exclude experiences caused by depression may have altered the relative frequencies of many adverse experiences. Each investigator would have had his own idea of what depressive experiences might comprise resulting in a lack of generality from one investigator to the next. Not surprisingly, many antidepressants and ansiolytic agents do produce adverse reactions which are known to be symptoms of depressions (e.g., insomnia, nausea, anxiety, tension, restlessness) leading to a possible underrepresentation of these effects."
* Tony DiCicco, an FDA Consumer Safety Officer, said the studies conducted by Eli Lilly to demonstrate Prozac's efficacy and safety were badly flawed. He stated, "This agency has discovered a flaw in the experimental design and execution of the fluoxetine studies. In the main efficacy trials, patients who were not doing well could be dropped out at the end of the second week and switched to fluoxetine (after breaking the blind and determining if the patient was on imipramine or placebo)... This led to the situation where an end point analysis would compare patients' scores after six weeks of treatment...leading to a biased comparison."
Meanwhile, the FDA's original efficacy review of Prozac found that the drug was no more effective than a placebo. The FDA, for reasons that are not clear, told Eli Lilly to reevaluate the drug based on fewer variables. The manufacturer did so, reducing the number of variables by two-thirds, and issued a new evaluation of Prozac's effectiveness. The FDA approved this new evaluation.
In fact, the FDA appears to have looked the other way in regard to several problems before Prozac's release. The FDA discovered in 1986 that Eli Lilly had withheld information about the onset of psychotic episodes on at least 52 patients during the drug's clinical trials. Yet no actions were taken against the manufacturer or Prozac. Documents also show that Eli Lilly and the FDA knew of 15 suicides that occurred during the drug's clinical trials, even though the Prozac label said that three people died during the trials.
Dr. Breggin, for his part, believes strongly that Prozac should not have been approved by the FDA for a variety of reasons.82 Among them:
* Eli Lilly hand-picked doctors to conduct studies of Prozac, and these doctors ignored evidence of its stimulant properties. Patients who became agitated received sedatives such as Klonopin, Ativan, Xanax and Valium, a procedure that Dr. Breggin says invalidates the studies. After all, the use of sedatives means that any effects on the patients were not caused by Prozac alone. As Dr. Breggin argues, "Basically, the FDA should have said, 'We're approving Prozac in combination with addictive sedatives.'"
* The number of people tested during Prozac's clinical trials is far fewer than the manufacturer claims. Eli Lilly has stated that 11,000 people took part in the clinical trials for the drug, including about 6,000 who took Prozac. But Dr. Breggin shows in his book that a mere 286 people completed the four- to six-week-long trials on which Prozac's approval was based.83 Eli Lilly has never challenged this information. "They've had me under oath in court, and they haven't contested a single word I've written in the book," Dr. Breggin says.
* The tests excluded people who were suicidal, psychotic or suffering from other mental and emotional disorders. These, of course, are the very types of people who would later be prescribed Prozac. Although Eli Lilly has not studied how many Prozac users have attempted suicide or committed suicide, adds Dr. Breggin, it could easily do so even today.
"One of the easiest things to study is whether your patients are alive or not. It's much easier to study that than whether they've gotten over their depression. That's a hard thing to judge. How do you know if somebody is feeling better or not feeling better? It's very complicated."
Evidence presented in the trial of Joseph Wesbecker also indicates that Eli Lilly knew that Prozac users had a much higher rate of attempted suicide than did patients taking placebos or other drugs. Dr. Breggin has testified as a medical expert in the trial of Wesbecker, who killed eight people, wounded a dozen others and then killed himself while he was taking Prozac.
Would a manufacturer sell an unsafe drug, and would the FDA approve it? Dr. Breggin says the answer is "yes" because psychiatry is a part of the medical industrial complex, which looks to market its products and services just like any other industry.
The fact is, hundreds of approved drugs later have major new warnings added to their labels or are withdrawn from the market. About 16 other drugs got the green light during the time that Prozac was approved, and nine of these have since had major changes to their labels. The FDA informs doctors, but not the public, that the approval of a drug does not mean it is safe.
Meanwhile, a drug's dangerous side effects may not be recognized during the testing stage because the FDA's individual studies usually consist of small groups of patients. For example, if 40 groups of 100 patients are tested (for a total of 4,000), the scientists may not notice a reaction in one patient.
THE FDA PANEL
Another problem is that FDA doctors may have close affiliations with drug companies. Dr. Breggin points out that Paul Leber, who approves psychopharmacological drugs at the FDA, is "a friend to Prozac." A statement in some of Eli Lilly's material even noted the relationship. Also, one doctor who voted in favor of the drug received payment from Eli Lilly to makes speeches about the drug's benefits and safety. "Dozens of doctors are getting paid by Lilly and doing clinical research for them. Nonetheless, they think they can sit fairly in judgment about whether Prozac is harmful or not," says Dr. Breggin.84
Furthermore, when the FDA convened a panel in late 1991 to review concerns about Prozac and violence, eight of the 10 panel members were psychiatrists. The livelihood of these professionals depends, in part, on the prescription of antidepressants such as Prozac, which raises questions about their objectivity in reviewing the safety of prescription drugs.
In fact, the FDA disclosed before the panel hearing that a number of the members had financial conflicts of interest because they had received grants from various manufacturers of antidepressants. One member even had grants pending from Eli Lilly; the CCHR also discovered that this member did not disclose his engagement to speak at seminars funded by Eli Lilly or two pending grants from antidepressant manufacturers. He had received some $4 million worth of research grants from such manufacturers in the eight years preceding the Prozac hearing.
In the end, nearly all of the panel members either had conflicts of interest or belonged to the psychiatric profession. The panel voted 10 to zero that there was no evidence proving that antidepressants were linked to violent or suicidal thoughts and behaviors.
According to the critics, the FDA panel did not acknowledge the importance of the "rechallenging" process in its review of Prozac. With rechallenging, patients who have experienced side effects which subside when they stop taking a drug begin taking it again to see if the same negative effects reoccur. If they do, the side effects in question can be closely linked to the drug.
Dr. Martin Teicher, the Harvard researcher, told the FDA panel of at least eight patients who had been rechallenged with Prozac and experienced violent, suicidal thoughts, establishing a connection between the drug and these effects. Dr. Teicher said that rechallenging could provide more definitive data about a drug, and more quickly, than do clinical trials, but the panel was not interested in the findings. What's more, when Dr. Teicher asked to present slides correlating Prozac with violent, suicidal thoughts, the panel refused to see them. It did, however, allow slide presentations that defended Prozac.
REFERENCES
82. Breggin interview, op cit.
83. Breggin, Talking Back to Prozac, p. 45-6.
84. Breggin interview, op cit.
