Guest guest Posted March 29, 2003 Report Share Posted March 29, 2003 Fri, 28 Mar 2003 16:50:00 -0500 WC Douglass Hard to swallow Daily Dose March 28, 2003 ************************************************************** A conspiracy of greed? Everyone's blue nowadays, it seems. In the last 15 years, the number of people seeking treatment for depression in the U.S has nearly doubled -- now 25 million per year. That's bad news -- but what's worse is that according to recent research, 90% of these people left their doctors' offices with a prescription for antidepressants. What we're dealing with here is a two-part problem: First, a dramatic rise in the incidence of depression; and second, the increasing reliance on drugs as the preferred treatment option. Of course, I've got some theories about why depression is running rampant these days, but I'll have to tell you about them in the next Daily Dose. What I want to talk about now is one reason why prescription drugs have become the treatment of choice -- and it's downright frightening... In these days of HMOs and group health plans, if you have insurance, your health care is usually funneled through a " primary care physician " (PCP) whose responsibility it is to diagnose the problem and -- if he can't treat it -- to refer you to a specialist. But in the case of depression, instead of referring patients to qualified therapists, the PCP often dashes off a prescription for a month's worth of antidepressant drugs. Sure, I'm skeptical of psychotherapy, but it beats harmful drugs -- and the vicious cycle of dependency they bring, with no real hope of a lasting cure. This " band-aiding " of depression symptoms could be doctors brainwashed by drug company propaganda into believing antidepressants are the best course of action. Or it could be that these PCPs are directed by the insurance companies to prescribe expensive, addictive drugs in place of other therapies. Neither reality is best for the patient, but one can be blamed on ignorance -- and the other only on a conspiracy. In either event, large forces with much to gain financially are influencing our doctors toward treatments that may not be the best course of action for you. Makes you wonder exactly what the drug company/insurance industry relationship is, doesn't it? It certainly doesn't seem to revolve around your good health... And that's enough to make anyone depressed. (I'll have more to say about antidepressants in the next Daily Dose, about what works and what's worthless.) ************************************************************** Statin drugs cause mental " static " I know I've mentioned cholesterol drugs a lot in the last year or so, both in Real Health and in the Daily Dose. But new research findings keep cropping up almost daily, it seems, that tell us new things about these harmful patent medications -- and their " benefits. " For instance, research unveiled at last fall's meeting of the American Heart Association revealed that a commonly prescribed " statin " drug for lowering cholesterol might actually impair patients' brain function -- even so far as to affect their ability to perform everyday tasks, like drive a car. The study pinpointed measurable decreases in attention span and psychomotor reflex speed among the subject group when compared to the un-medicated control group... But here's the really incriminating part: Those patients who experienced the greatest decreases in blood cholesterol also suffered the greatest levels of impairment! Interesting, huh? I mention these findings to you now because I know the mainstream press will never pick up the story -- but also because some medical authorities estimate that in the very near future, half of the adult U.S. population could be taking cholesterol-lowering medications. That's right -- if conventional doctors and the " drug thugs " have their way, every other one of us will be stumbling around in a statin stupor! But what's not clear is whether the impairment is caused by the drugs themselves -- or the lack of cholesterol... I suspect it's the latter. Why? Because low cholesterol levels have been linked to numerous other health issues directly related to the brain -- things like violent behavior, depression, mood swings, stroke risk and other problems. Maybe now, we should add " impaired brain functioning " to that list. I've said it before, and I'll say it again now: Unless your cholesterol climbs over 300, forget about it -- even the " ratio " of LDL to HDL that so many conventional doctors make such a fuss about. For heart health, concentrate instead on DHEA, testosterone (for both men and women), and homocysteine levels. And be sure to supplement with plenty of folic acid, B vitamins, and CoQ10, too... Just leave the statin drugs alone -- unless you're suffering from an excess of IQ or terminal euphoria. It's not easy being blue, William Campbell Douglass II, MD ************************************************************** Copyright ©1997-2003 by www.realhealthnews.com, L.L.C. 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Guest guest Posted April 24, 2003 Report Share Posted April 24, 2003 SSRI-Research , JustSayNo wrote: Hard to Swallow Read the ads and you'll think relief from the black cloud of depression is just a pill away. But if you consult the scientific record and look at the medical trials the pills have gone through, you'll see a much scarier story. http://www.washingtonian.com/health/hardtoswallow.html By Thomas J. Moore Thomas J. Moore is the author of four books about health and medical care. His book, Prescription for Disaster, (published by Simon & Schuster, 1998) focuses on the risks of the most widely used prescription drugs. " Prozac seemed to give social confidence to the habitually timid, to make the sensitive brash, to lend the introvert the social skills of a salesman. " So writes psychiatrist Peter Kramer in his book Listening to Prozac. Such glowing accounts have helped make antidepressants such as Prozac, Paxil, Zoloft, Effexor, and Serzone among the best-selling drugs in the world. Yet here, in similar language, is how Johns Hopkins psychiatrist Kay Redfield Jamison describes an episode of mania in An Unquiet Mind, a memoir of her long battle with mental illness: " Shyness goes, the right words and gestures are suddenly there, the power to captivate others a felt certainty. There are interests found in uninteresting people. " These statements are so strikingly alike because both describe a serious mental illness, no matter how attractive Kramer makes it sound. During manic episodes, the habitually timid may attack a police officer; armed with new social confidence, an introverted woman may brazenly solicit men in a bar. A serious episode of mania typically ends in a locked psychiatric ward. In fact, according to their manufacturers, Prozac, Paxil, Zoloft, Effexor, Serzone, and other antidepressants may trigger mania, or less severe hypomania. Fortunately, mania is an infrequent side effect of drugs for depression. What is distressingly common, though, is the tendency of both doctors and patients to overestimate the benefits of these drugs while ignoring their risks. How does the hype about antidepressants compare to the scientific record? The drugs are touted as effective for the vast majority of depressed patients. Yet they routinely fail to produce a measurable benefit in clinical testing. Prozac especially is claimed to be relatively free of side effects. Yet in reports to the Food and Drug Administration, Prozac has been linked to more serious adverse reactions than any other drug in America over the past decade. And other antidepressants are little safer. Antidepressants are said to be non-habit-forming. Yet in the first large study, more than one out of three patients experienced withdrawal effects. The safety of antidepressants is supposedly proven by the fact that they have been taken by more than 20 million Americans. Yet virtually no meaningful research has been conducted on their long-term risks. The danger of suicide is widely cited as a reason to treat depression with these drugs. Yet there is no evidence that antidepressants prevent suicide--and dark hints that they may even encourage it. With antidepressants, side effects are more common than success stories. Here is what a patient named Greg had to say about Zoloft: " Side effects? Just about all of them. The ones that stick around? Dry mouth, some hot flashes. I still get unusual cases where I'll wake up at three in the morning sweating. I have drowsiness and difficulty focusing for the first five hours after taking a dosage. " (Greg's comments and those of some of the other patients quoted in this article were obtained through the Internet. To protect privacy, last names have been omitted.) The fact is that antidepressant drugs are overrated by many consumers and doctors, overprescribed because of aggressive marketing, and among the most toxic drugs in widespread use as measured by the number, variety, and severity of adverse effects. What's more, millions of Americans who think they can testify to the benefits of antidepressants are being misled by their own feelings. Doctors, if they rely on their clinical experience, are similarly deceived. Why? Because in the treatment of depression, the placebo effect is very large. Scientific testing shows that roughly two out of three people who report a " marked " improvement on an antidepressant drug would have done equally well on a harmless placebo--and they wouldn't have to suffer such side effects as sexual dysfunction, anxiety, insomnia, sweating, and nausea. An objective appraisal of antidepressants would be easier if global pharmaceutical companies didn't depend so heavily on their sales. Take Eli Lilly: Last year, Prozac accounted for about 30 percent of its total sales and probably an even larger share of its profits. Like tobacco and beer companies, the pharmaceutical industry spends more for advertising and promotion than for manufacturing or research. This means billions are available to polish the image of products--and to combat critics. For the facts about antidepressants, the best place to look is the Food and Drug Administration. By law, drugs have to be extensively tested before being marketed. The tests are evaluated by FDA doctors, chemists, and statisticians. This article focuses on two of the newest drugs for depression, Serzone and Effexor, because--as new drugs--they ought to be tested to high standards and might offer advantages over Prozac, now in its tenth year. But what does the record say? An examination of the risks and benefits of a drug must begin with a look at the medical problem it is intended to combat. Those who have not personally experienced major depression should not underestimate the severity of the disorder. Few afflictions are so capable of causing suffering. Here's how Charlotte Brontë described an episode of depression in her novel Villette: " Indescribably was I torn, racked, and oppressed in mind: Galled was my innermost spirit with an unutterable sense of despair about the future. Motive there was none why I should try to recover or wish to live; and yet quite unendurable was the pitiless and haughty voice in which Death challenged me to engage his unknown terrors. " Modern psychiatry has reduced Brontë's poetic account of a dark cloud over the human spirit into a dry list. A " major depressive episode " is defined as a period of two weeks or longer in which a person loses pleasure in all or almost all activities. To this may be added fatigue, a feeling of worthlessness, inappropriate guilt, anxiety, difficulty sleeping or excessive sleeping, indecisiveness, inability to concentrate, or thoughts of suicide. By the medical criteria, just one of these episodes justifies a diagnosis of " major depressive disorder. " The number of people who suffer from this mood disorder has been poorly studied and is often exaggerated, either to sell drugs or to advance depression to a more prominent position on the list of disorders worthy of media attention, aggressive medical treatment, and public funds. In a survey of 18,000 people funded by the National Institutes of Health, 1.5 percent of the population was suffering from major depression when interviewed, and 4.5 percent had experienced major depression at some point. At any time, about 4 million people in the United States suffer from the disorder. Millions more suffer less-severe episodes, often in connection with bereavement, divorce, or other life stresses. The oppression of the human spirit that is called depression may be measured by a numerical scale of symptoms that ranges from 0 to 52. Called the Hamilton Depression, or Ham-D, scale, it consists of 17 scored items. A person with a Ham-D score of less than 6 is roughly normal. A Ham-D score of 20 or higher indicates major depression. The strength of this approach is that psychiatrists everywhere can use the same protocol to evaluate patients and ought to get at least similar results. Under controlled conditions, raters agreed on diagnoses about 80 percent of the time. The scale isn't perfect, but Ham-D is a reasonably precise tool for diagnosing depression and measuring improvement or deterioration. Hard to Swallow Page 2 of 6 Given that major depression is a mood disorder involving great human suffering, the next question is whether antidepressants relieve this psychic burden. Some answers come from patients who have taken them. Jeanne describes " the wonderful world of Prozac. To me it felt like laying back in a bed of rose petals and staying there all day. " Sean said, " My daughter was on Prozac for three months, and it made her worse. " Pauolo said, " I have found Prozac to be extremely helpful. I feel perfectly normal for the first time in my life. " Jane said, " It was as though the color had gone out of my personality. Once I came off, I became myself again. " Select a few glowing stories, and Prozac sounds like a drug that helps many people. That is what Peter Kramer did in Listening to Prozac. Fill a book with horror stories, and most of its readers wouldn't touch an antidepressant. Such anecdotes, in short, tell us little about whether these drugs work. Reliably observing the effects of a drug on something as ephemeral and variable as depressed mood requires the most rigorous rules that science can devise. We have no laboratory tests to measure mood. Mood can be transformed in an instant, and even the most compassionate observer still can never know what another person truly feels. Many depressed people have learned to fool their associates, perhaps sometimes even themselves. Finally, the appraisal of drug effects has long been contaminated by our need to believe there is something available to relieve our suffering, reduce our pain, hasten our return to health. Why in the name of health did so many people once consume foul-tasting concoctions, deadly arsenic, or violent purgatives? Because for centuries doctors and patients so hoped for a cure that they thought they observed people getting better after treatment. Somewhere deep in the human spirit people want to believe in medication, and it takes all the objectivity modern science can muster to separate hopes and wishes from genuine drug effects. The procedure for testing a drug for depression is something like a courtroom jury trial. It is a drama played out according to detailed rules that take years of training to master. Like a prosecutor, the researchers must declare in advance exactly what they expect to prove. Every participant must consent in writing. The judges are the medical and statistical experts at the FDA, as well as outside experts drawn from medical schools and research centers. The official record may be thousands of pages long. The clinical trials of the antidepressant drug Serzone serve as an example. To win approval to market Serzone, Bristol-Myers Squibb had to conduct at least two successful trials with humans. To do that, the company contracted with outside research doctors who oversaw the trials at various clinics, doctors' offices, and medical centers throughout the United States and Canada. The rules can change between clinical trials but must be identical for every patient within each trial. In all, more than 3,000 patients took part in the testing of Serzone. More money is at stake in these clinical trials than in all but the very largest courtroom cases. A drug that fails will mean tens of millions of dollars wasted; a big success can bring billions of dollars in profits, enough to sustain a global pharmaceutical giant for years. With so much at stake--including human lives--a modest amount of checking and double-checking occurs. The way the system works can be seen in the Serzone clinical trial known as CN104-002. It began with a group of similar patients who had been diagnosed with major depression and consented to join this experiment. It was important to make sure that healthy patients were not accidentally included. No drug works when given to people who don't have a medical problem needing treatment. The most extremely ill--those openly suicidal--also were excluded. A drug-research institute in Southern California recruited 180 patients with depression so serious that, on the average, the participants rated 24 on the Ham-D. At random, the patients were assigned to receive either Serzone or a seemingly identical placebo. Except for a group of safety monitors, no one in the experiment was supposed to know which patients were given Serzone and which were given the placebo. Random chance is the fairest way of selecting a jury to take the drug while maintaining a nearly identical untreated group for comparison purposes. The experiment continued for six weeks with investigators evaluating every patient on a weekly basis and scoring the results. Bristol-Myers hoped to find " marked improvement " among those treated with Serzone. This was defined as a 50-percent drop in the Ham-D depression score. Since the average depression score was 24, the company was hoping most patients' scores would drop by 12 or 13 points over six weeks. Although six weeks seems brief for a drug likely to be given for months, it is at least long enough to detect an initial effect. What results did Serzone achieve? Six weeks after the Serzone trial began, there was no difference, in statistical terms, between the patients treated with Serzone and those given the placebo. The average patient on Serzone improved, but so did those getting a placebo. The placebo group improved by 11 points on the Ham- D scale, the Serzone patients by 12 points--a difference so small that it might have occurred by chance. In testing results submitted to the FDA, Serzone failed to show a clear benefit in six of the eight clinical trials. Three more clinical trials were discontinued before results were available. In some cases FDA evaluators thought they saw an explanation for the lack of effect. In three of the failures, the FDA was persuaded that the dose was too low. Since even a promising drug will have no useful effect at the wrong dose, Serzone was tested further at a higher dose. One of these high-dose trials failed by everyone's evaluation, and two more were borderline. However, two other trials were declared a success. If six Serzone trials failed or were inconclusive, what results did the two claimed successes achieve? In one " successful " trial the placebo patients showed a dramatic improvement. Their depression scores dropped 17 points in six weeks. Serzone patients didn't do as well, with average scores improving 14 points. On this data, a rational patient would choose to take the placebo rather than the drug. But as analysts pored over the details, they spotted an interesting fact. Overall, 88 percent of patients in the trial had been recruited at one large center in Canada and the remainder in three smaller centers, also in Canada. The largest placebo effects had been observed in the patients at the three smaller centers. When the results of these three smaller centers were excluded, the patients in the test appeared to benefit from Serzone. Excluding results unfavorable to Serzone after the fact was like conducting a jury trial and, if no guilty verdict resulted, allowing the prosecution to remove the jurors with doubts. But even when the most unfavorable results were excluded, Serzone patients' depression scores improved by 13 points, the placebo patients' by 12. Yes, Serzone was now slightly ahead, but again this small difference could easily be explained by chance. How then could anyone claim Serzone was effective? It turns out there is another way to score the results. A problem that plagues clinical trials for depression is that patients drop out in large numbers because of toxic side effects or for other reasons. In this trial, one-third of the patients had quit before the six-week period ended. Under alternative statistical rules, it was permissible to pretend that those who dropped out had continued to the end of the trial. The final results included all the scores, even for those who had quit after one week. Suppose, for example, that a Serzone patient had improved dramatically at the third-week examination but was hospitalized the next week for severe adverse effects. The three-week score showing a great benefit still would be included--and there would be no penalty for the participant's not continuing to the end. This is using statistical adjustments to try to prove an effect that was not detected by direct scientific observation. What's more, it makes the test an unrealistic estimate of what will be achieved in actual use. Antidepressants are prescribed for months and sometimes years. Nonetheless, with these more lenient scoring rules, and after eliminating the centers where the results were poor, Serzone appeared to have a beneficial effect. Scores for patients taking the drug improved by 11 points, while the placebo patients improved by just 7 points. Yet another factor needs to be considered. One of the most common adverse effects of antidepressant drugs is to make anxiety and insomnia worse--or to add these problems to the symptoms already present. To combat this expected adverse effect, the patients were allowed to take a sedative called chloral hydrate. This is certainly humane, but if a depressed patient is suddenly sleeping better and freed of the terrors of the night, do we credit Serzone or the sleeping pills? In the " successful " clinical trial of Serzone, not only were patients allowed to take sleeping pills; 14 of them also took other drugs, including tranquilizers and other antidepressants. Could it have been the other medication that accounted for the small effect claimed for Serzone? The second Serzone trial said to be a success required an even more drastic statistical adjustment. A single investigator supervised the trial in six psychiatric practices and seven family practices, all on the East Coast. When the overall results were scored, the trial was once again a failure. However, while the patients recruited from the family-practice sites appeared to benefit, those recruited from the psychiatric sites did not. The solution? Exclude the psychiatric patients. At the core of the scientific method is the requirement to produce, by direct empirical observation, a result that can be replicated. Yet Bristol-Myers could not replicate the results even using the identical protocol, supervised by the same investigator. The results for the second drug--Effexor--were not much more impressive. Manufacturer Wyeth-Ayerst conducted three clinical trials under a special protocol that allowed the investigators to individualize the dose for each patient. In two out of three trials, Effexor still failed to produce a benefit as measured by Ham-D scores at six weeks. Once again the FDA allowed the rules to be changed after the fact to allow Effexor to squeeze through. It counted as successful a clinical trial that had shown a benefit at four weeks--but these apparent benefits had disappeared by the sixth week. As it had with Serzone, the FDA provided a generous interpretation of its own rules to " prove " Effexor effective in two clinical trials. I challenged the quality of the scientific evidence for both drugs in an interview with Thomas P. Laughren, an FDA medical doctor who, as the team leader for evaluating psychiatric drugs, had reviewed both Serzone and Effexor. While conceding that the effects of these drugs were " modest, " Laughren noted that the drugs had been evaluated by the FDA's own statistical specialists and then reviewed by an advisory panel of psychiatrists and drug-testing experts. All concluded the drugs were effective, he said. It is revealing to observe these independent experts in action. On July 19, 1993, 11 members of the Psychopharmacologic Drugs Advisory Committee met to deliberate on the fate of Serzone. Paul Leber, a medical doctor and director of the FDA division that evaluated the drug, led the discussion. Very few drugs are sent to the committee unless approval is considered likely. Still, one would think that Serzone faced an uphill battle. By the simplest box score, it had failed in six of eight tries. After the committee got a briefing on the clinical testing, Leber asked, " [Does] the evidence as a whole [show] the drug has the effect claimed for it? So that gives you great latitude in interpreting the entire data set. " These words were scarcely out of Leber's mouth when it looked like Serzone might be in trouble. The final decision to approve or reject Serzone would be made by Leber's boss, an FDA doctor, Robert Temple, whose title was director of the Office of Drug Evaluation I. Temple seemed to want to emphasize a strict standard. " It needn't be mindless, " Temple told the committee. " The only limitation is that we generally expect replication. But that doesn't mean that if you get two studies out of four that work, it is okay. " This sounds like the death knell for Serzone. By the FDA's rules, Serzone produced no measurable benefit six times. But this did not prove a fatal flaw to the chairman of the advisory committee, Carol Tamminga, a professor of psychiatry at the University of Maryland. She found a distinction between studies that were " negative " and those that " failed. " " There is only one negative study in this data set as I read it, " Tamminga told the panel. " The other failed studies are where there was no difference defined between placebo and the active control. " Tamminga was referring to the fact that in some trials Serzone was also compared with another, older antidepressant as well as to a placebo and that neither drug proved effective. In effect, she seems to have assumed that if Bristol-Myers had done the experiment properly, at least the older drug would have looked beneficial. Dennis S. Charney, a professor of psychiatry of Yale University, agreed with Tamminga: " It is that data that leads me to say it is an effective drug. But I do worry about the large number of failed studies. " Next, Regina Casper, a professor of psychiatry at Stanford University, noted the obvious. " We do not have overwhelmingly strong support for this drug being a strongly effective antidepressant, " she said. As happens in many committee meetings, the discussion meandered. But in the end, all but one member of the advisory committee voted to declare the drug effective. Still, some of these drug experts seemed nervous about what they had done. Robert Temple, the FDA doctor who would later approve Serzone, was concerned about new risks now being discovered about antidepressants on the market, especially their capacity to interact with other drugs and food. " It is very daunting, " Temple said. " The more you look, the more you discover. And the limits of what we are going to discover are not nearly over. " Temple had reason to feel daunted. Once approved, the risks of drugs may continue undetected for decades. A dramatic example came four years after Temple made this comment in 1993. The diet drugs Pon-dimin and Redux were hastily withdrawn after the FDA found evidence that more than 30 percent of the patients checked had evidence of damage to their heart valves. Pondimin was approved in 1973, but no one noticed the capacity of the drug to injure heart valves until someone looked 21 years later. As Temple said, the more you look, the more you discover. But that concern prevailed for only an instant. Soon the onus was on consumers. Temple said, " It seems that consumers need to start rethinking that there is a pill for every ill and that they are all safe. We are starting to understand that things are more complicated than we once thought. " Tamminga, the chairman, agreed: " That would be a superb message. " The real message the FDA and the experts were sending was that the efficacy standards for approving drugs for depression were remarkably low. A drug that had a marginal effect at best, and by strict rules no beneficial effect at all, was deemed acceptable for aggressive marketing to doctors and patients. Serzone's repeated failures to achieve the expected benefits would not be included in the information disclosed to doctors. I asked Bristol-Myers to comment on Serzone's efficacy and was granted an interview with Darlene Jody, a psychiatrist and senior medical director for central-nervous-system drugs. It was clear that we both were looking at the same clinical-trials data. " Two studies of Serzone were positive, " she said, " and two were supportive. " Asked about excluding the results of some centers and getting different results from different measurement methods, she said, " In psychotropic drugs it is not uncommon for all drugs to have these types of exceptions. " Just one or two individual trials do not represent the whole body of scientific evidence, she said. " There is an accumulation of data to demonstrate that the drug has a positive effect on treatment outcome. " Jody also said that since FDA approval, Bristol-Myers had completed six more trials comparing Serzone to Paxil, Prozac, and Zoloft: " In not one of these trials is Serzone less efficacious, and it is possibly more efficacious. " Wyeth-Ayerst Laboratories responded to questions about Effexor with somewhat similar points. Richard Rudolph, a physician who is senior director of clinical research for the company, said, " You need to understand that in the history of submissions for psychoactive drugs, generally sponsors have had to submit multiple trials to get two positive results. " There are many reasons why clinical trials fail, Rudolph said. " There is a high placebo-response rate. The sample size is inadequate. The patient population is insensitive to the effects of the drug. " Effexor, he said, also had been compared to Prozac and other antidepressants since FDA approval and had demonstrated comparable effects. What these company representatives are in effect saying is that patients do very well on placebos. They are saying the expected effects are so small and unpredictable that every drug company has to plan for frequent failures. Finally, they are saying that all antidepressants are roughly the same in effectiveness. This is likely true, but it means all the similar drugs have the same limited benefit. If antidepressant drugs had no adverse effects, harmed no one, and never spoiled a morning, a day, or a life, then turning loose the mighty marketing engine of the drug industry on such meager evidence might be an acceptable risk. The drugs might help some people. And many would be comforted when a doctor they respected prescribed a pill to relieve their suffering. As one observer put it, " False hope is better than no hope. " However, antidepressant drugs are notable for a variety of adverse effects from which a large fraction of patients suffer. When the participants in Effexor's clinical trials visited the clinic, their symptoms of depression were not the only item evaluated. They also answered a long series of questions intended to identify symptoms that might signal a dangerous adverse effect. Periodically, they would have their blood and urine tested and their heartbeat monitored. These medical tests might provide the first evidence that a drug was injuring the liver, damaging the kidneys, or interfering with the operations of the heart. If the doctor discontinued the drug because of an adverse effect, this would be noted. If a patient failed to appear for a scheduled appointment, an inquiry is supposed to be made. During the testing of antidepressant drugs, a few patients do not appear for appointments because they have shot themselves, hanged themselves, or died of an intentional overdose. It is from this testing data that the safety profile of a new drug emerges. This scrutiny also can prevent a promising new drug from becoming the victim of a bum rap. For example, 23 percent of the patients taking Effexor reported having headaches. So does Effexor cause head-aches? Probably not: 23 percent of those on placebo also reported headaches. The profile of adverse effects that emerges from such data will not be perfect, but it will be more accurate than anecdotes. When Effexor patients were asked about nausea, a genuine side effect did emerge. Thirty-six percent of the Effexor patients reported being nauseated, compared with 9 percent of the placebo group. When asked about sexual impotence, 5 percent of men taking Effexor reported that problem, but none of the placebo patients. When placebo effects are subtracted, the most common side effects can be accurately mapped. Effexor had harmful effects on patients' appetites and on their digestive tracts. At least 27 percent experienced nausea, 8 percent reported constipation, and 9 percent lost their appetite so completely that they were classified as having anorexia. Effexor also had many adverse effects on the heart. On the average it made hearts beat faster by three beats a minute. It also raised blood pressure. Over a year's time, the FDA estimates suggest that about 8 percent of Effexor patients might require treatment for high blood pressure. Effexor raised blood pressure in many patients by more than the typical blood-pressure drug lowers it. Overall about 11 percent of men reported sexual problems related to Effexor, divided equally among those who reported outright impotence and those who experienced abnormal or painful ejaculation. Another 2 percent of both sexes reported decreased sex drive. None of the placebo patients reported any of these sexual problems. It was in the very system to which Effexor was targeted--the central nervous system--that the most unpredictable adverse effects could be observed. Effexor made about 14 percent of the people who took it sleepy or sedated. Here is one experience: " I am taking 150 mg. of Effexor, " Donna said. " I have recently started back to work, and I can hardly keep my eyes open. I find that around 10:30 AM or so I start to get so tired and have minimal concentration. " While Effexor made one in seven people sleepy or sedated, it made an even larger number nervous, anxious, or unable to sleep. Overall, 8 percent reported insomnia, 8 percent nervousness, and another 2 percent anxiety. Ten percent reported breaking into abnormal sweats, and 11 percent experienced dry mouth. Serzone's adverse effects were roughly similar but included possible disruption of higher mental functions. After adjusting for placebo, from 1 to 5 percent of those testing Serzone reported one or more of these symptoms: confusion, impaired memory, abnormal dreams, decreased concentration, lack of coordination, psychomotor retardation, and tremors. But Serzone appeared relatively free of adverse effects on sexual activity--a key marketing point for the drug. How severe are these problems? To obtain relief from major depression, many people might tolerate a little difficulty falling asleep or a dry mouth some of the time. But in 19 percent of the Effexor patients the problems were so severe that the drug had to be discontinued before the six-week trial ended. By this measure, the demonstrated toxicity of Effexor is above average for antidepressants: 15 percent had to discontinue Prozac and Zoloft because of adverse reactions; 16 percent discontinued Serzone; and 20 percent, Paxil. (Wyeth-Ayrest said it expects to market a sustained release version of Effexor that will have a better side-effects profile.) A drug so toxic that nearly one in five has to stop therapy would not seem to be a chemical that can be released to the public with confidence that it will at least do no harm. Nor is such toxicity typical of drugs generally. For example, the cholesterol-lowering drug Zocor was tested among 2,223 people for more than five years, with only 126 dropouts because of adverse effects. Fosamax was tested for two years to measure its effect on osteoporosis with only 4 percent dropping out because of the --- End forwarded message --- Quote Link to comment Share on other sites More sharing options...
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