Lesley Elliott




History of Weight Loss

The Drugs Defined

A Phen/Fen Study on the Internet

A Redux Study on the Internet

Internet Claims

Conclusions About Internet Claims

A Study on Appetite Suppressants and Primary Pulmonary Hypertension

A Study on Phen/Fen and Valvular Heart Disease

Conclusions on Clinical Studies

The FDA and Phen/Fen


  History of Weight Loss

Since the beginning of time, weight loss has been a concern for people throughout the world. In the Nineties, it has become the focus of numerous advertisements, articles, and media scams. Infomercials selling everything from exercise equipment to magical creams promising results of cellulite-free thighs are plastered across late-night television in perfect view for anyone. Along with all of this, diet pills once again became the fad in 1994 with phen/fen. This was the first time since the 1960s. Then, in 1996 Redux hit the market (http://www.mesomorphosis.com/obesityclinics.htm). The advertisements for these pills were aimed towards those people who were obese and wanted to lose weight and get results. What is remarkable are the differences that range among these ads. Some promised results without the dangers of the side effects, while others offered detailed information about the possible risks involved in using the medications. This leads to a confusing situation that leaves people wondering what to believe. Further examination in to this topic shows startling evidence that Fenfluramine and Dexfenfluramine can cause serious health problems which can be fatal. Looking at all of the different and confounding data, people are sure to be confused about what is really true about these diet pills. The Drugs Defined

Before understanding the claims that people have made about these drugs, the drugs themselves must be defined in terms of what the drugs are and how they work. The phen/fen diet pill combination is composed of two drugs, neither of which are new. Phentermine (phen) and Fenfluramine (fen) have both been prescribed separately by doctors for many years and are FDA approved (http://www.netek.com/weightwise/phen.htm). Both are anorexics, which help inhibit appetite in two different ways. Phentermine is a stimulant that acts through noradrenergic and dopaminergic pathways. This results in decreased appetite, which in turn leads to less eating. Fenfluramine acts through serotonergic mechanisms that induce increased satiety (http://www.weight.com/phenfen.html).

Redux, or Dexfenfluramine, is the first drug in more than twenty years that the FDA has approved for weight loss. It is a serotonin reuptake inhibitor and releasing agent (http://www.netek.com/weightwise/phen.htm). This anorexic drug, which has been used for years in Europe, causes the release of serotonin in brain cells. The actual action of serotonin is uncertain, but increased levels appear to stimulate the part of the brain which controls mood, sleep, and body temperature among other functions (http://www.weight.com/Dexfenfluramine.html). A Phen/Fen Study on the Internet

When looking at the effectiveness of phen/fen in losing weight, one study done by Michael Weintraub provides considerable information. The study took place over 210 weeks. The patients ranged in age from 18 to 60 and weighed between 130% and 180% of their ideal weights. Otherwise, these patients were in good health. They had not been taking any long-term medication, and they did not suffer from high blood pressure, diabetes, or any other chronic disease. The medications used were Phentermine resin (15 mg) in combination with Fenfluramine (60 mg). During the study, behavior therapy with trained professionals was included along with counseling by dieticians to help limit calorie intake. This was kept between 1500-1800 kcal per day for men and 1000-1200 kcal for women. The patients were also started on an exercise program. At regular intervals throughout the study, physicians saw the participants to monitor the progress. At 34 weeks, those patients who were treated using a placebo had an average weight loss of about 10 lb. Those who were treated using the medication experienced an average weight loss of about 30 lb. Between the 34th and 104th weeks, all of the participants were placed on the medication. Those on continuous medication saw an average loss of 27 lb. Those on intermittent medication averaged a 25 lb loss, and those patients placed on augmented medication experienced an average loss of about 14 lb. The average weight loss of the 83 patients who remained at week 104 was about 23 lb. Between the 104th and 156th weeks, the medication dosages varied, and results showed that from week one, the patients had lost weight overall but had gained weight since week 104. The amount of weight gained since the 104th week ranged from 2.7 kg to 7.6 kg. At this point, the average weight lost since the start of the program was 21 lb. Between the 190th and 210th weeks, the patients were tapered-off the medications, and everything else continued. At the end, only 48 patients remained, and the average weight loss was only 3 lb; however, some were 10% or more below their starting weight. Among other conclusions made from this study, it was determined that weight loss peaked at the 34th week with an average of 14 kg (http://www.weight.com/phenfen.html). A Redux Study on the Internet

In a study conducted on Redux, many questions about the results of this drug were answered. The International Dexfenfluramine (INDEX) Study, the largest controlled study using Dexfenfluramine, placed patients on the medication or a placebo for one year. All of the patients were also placed on a program including behavior modification and dietary instruction. Patients placed on the placebo showed an average weight loss of about 16 lb. Those on the medication had an average weight loss of about 21 lb. The group on the medication lost an average of about 5.75 lb more than those on the placebo (http://www.weight.com/Dexfenfluramine.html). Internet Claims

In some advertisements appearing on the Internet, the claims made seem to imply that there are hardly any noticeable side effects involved while taking the phen/fen combination or Redux. In an advertisement from WeightWise Health Centers, after giving information about the specifics of the medications, the company says of Phentermine and Fenfluramine, "When you put them together they balance each other out. Because of that, they do not have the same side effects as the old fashion diet pills. They do not make you feel jittery or nervous and they are not habit forming. They suppress your appetite. You are definitely not hungry on this program" (http://www.netek.com/weightwise/phen.htm). Of Redux, it says, "Redux therapy has been associated with decreased appetite and may make you feel full and lessen your desire to eat" (http://www.netek.com/weightwise/phen.htm).

Another claim appearing on the World Wide Web says that the phen/fen combination heals patients with a wide variety of afflictions previously thought to be incurable. It claims that one of the most popular uses for the phen/fen drugs is in the area of weight loss "finding them to be far more effective than the dozens of weight programs, herbal remedies, and competing treatments on the market today." The article goes on to say the product "works because it eliminates psychological cravings for food, cuts down excessive hunger, and reduces depression-related ailments that result in eating disorders, such as bulimia and anorexia" (http://www.fenphen.com/hope.html).

Yet another claim on the Internet refers to a Dr. Pietr Hitzig. This particular article states that those patients on the Hitzig fen/phen program have dosages which are balanced for their individual, personal needs. Through this man’s program, the doses are usually half of what is prescribed by other doctors. The article continues by claiming that the risks of fen/phen are not typically caused by the medicine itself, but they are caused by lack of education of the doctors who tend to prescribe the same set dosage for all of their patients (http://www.fenphen.com/crisis-breaking.shtml).

In other documents found on the Internet, the information provided was more detailed in the inclusion of side effects and possible risks involved in taking either Redux or the phen/fen combination. One says, "Dexfenfluramine appears to cause a serious medical condition called Primary Pulmonary Hypertension that affects an (estimated) 1 in 17,000 patients treated for longer than 3 months." This same article also says that the medication in high doses has been shown to cause damage to the brain serotonin neurons (http://www.weight.com/Dexfenfluramine.html). More common side effects mentioned in another article include dry mouth, diarrhea, and drowsiness. Stopping Redux may induce fatigue, insomnia, and weakness accompanied by headache (http://pharminfo.com/cgi-bin/print_hit_bold.pl/pubs/msb/redux.html). Taking Phentermine may produce side effects of nervousness, irritability, insomnia, agitation, dizziness, dry mouth, constipation, elevated blood pressure, and rapid or irregular heartbeats. Fenfluramine may produce drowsiness, sedation, diarrhea, and depression, which are somewhat opposite those produced by Phentermine (http://www.weight.com/phenfen.html). Conclusions About Internet Claims

When all of the claims made about these medication programs are examined, it can be seen that the extent to which they differ is great. Some claim to provide medical programs that are safe and have few if any side effects, while others warn of possible dangers involved. Examining these claims closely shows the contradictions that appear from to ad to ad. This tends to be very misleading. The public is bombarded by the overwhelming number of claims that appear on these three pills leading them to a state of confusion on which contains the right information. As newer information on each of these medicines enters the media, people will soon be able to make more sound and educated judgments on whether or not phen/fen and Redux are a safe, effective, and healthy way for them to lose weight. A Study on Appetite Suppressants and Primary Pulmonary Hypertension

The next question asked when speaking of Phentermine and Fenfluramine is what is the published medical research saying? In a study found in The New England Journal of Medicine, the effects of anorexic drugs on Primary Pulmonary Hypertension are studied. The study done was a prospective case-control study conducted in four countries, France, Belgium, the United Kingdom, and the Netherlands. The patients included men and women who met the following criteria: they were 18 to 70 years old, had lived in the country where they were studied for more than six months, could participate in the interview, and did not have any other chronic or life-threatening disease (Abenhaim et al. 1996).

The patients that the doctors conducting the study recruited were those people who were diagnosed with the condition from September 1, 1992 through September 31, 1994. A panel of reviewers next looked over the medical records and history of the patients; they were kept unaware of those who had used anorexic drugs and those who had not. The panel then placed each person into one of these three groups: patients with definite Primary Pulmonary Hypertension, patients with probable Primary Pulmonary Hypertension, and patients who were not considered appropriate for the study (Abenhaim et al. 1996).

For each patient with Primary Pulmonary Hypertension there were four control patients who were randomly selected from lists of consecutive patients seen by the same general physician normally seen by the patient with the condition. The control patients were matched to the patients with respect to age, sex, and the number of visits to the physician per year (Abenhaim et al. 1996).

Next in the study each patient went through an extensive interview with an interviewer who had no medical background and did not know the purpose of the study. The interviewers asked questions about the following: demographic characteristics, medical history, surgical history, obstetrical history, and exposure to drugs. Data on the reported exposures to drugs was recorded on a data sheet in chronological order if such exposures occurred after August 1, 1989. Only when the patients had exposure to the following drugs did analyzing of drug exposure take place: antihypertensive drugs, oral contraceptives, thyroid extracts, and anorexic agents. Of the anorexic agents the following were considered: derivatives of Fenfluramine, amphetamine-like anorexic agents, and compound preparations of appetite-suppressant drugs and other drugs used for weight loss. Patients were then classified further as whether or not they had been exposed to a given risk factor. If exposed before the index date, the patients were described as having a definite exposure. These people were further placed in groups, depending on when the exposure occurred. If the exposure was during the twelve months before the index date the patients were classified as recent users. If the exposure had ended twelve months earlier, the patients were classified as past users. If exposed during an indeterminate time or during the same month as the index date, the patients were placed in the group classified as having had possible exposure. Those patients who were exposed after the index date were said to be unexposed (Abenhaim et al. 1996).

The study included exposure to appetite suppressants, weight-related confounding variables, and other variables thought to be possible risk factors. Weight-related variables considered included the patient's highest lifetime body-mass index, the behavior aimed at losing weight, and the use of thyroid extracts. Other variables thought to be risk factors were the use of cocaine, IV drugs, or both, treatment for systematic hypertension, and smoking. In a separate analysis of women, the use of oral contraceptives and pregnancy during the year of the index date were considered as well (Abenhaim et al. 1996).

One hundred thirty-five patients with Primary Pulmonary Hypertension met the criteria to be included in the study. Twenty-six more had already died or were too sick to go through the interview process. Out of the 135 patients considered by the panel, 23 were said not to be likely candidates for Primary Pulmonary Hypertension, 2 could not be found to follow-up, 2 declined to continue, and 13 could not be interviewed or their data reviewed. 95 patients remained, 80 with definite Primary Pulmonary Hypertension and 15 with probable Primary Pulmonary Hypertension (Abenhaim et al. 1996).

The most notable findings concerned the use of appetite suppressants as a risk factor for Primary Pulmonary Hypertension. This was found to be especially true if the product was used longer than tree months. This study found that "the risk of Primary Pulmonary Hypertension seems to increase steadily with the quantity of appetite suppressants used" (Abenhaim et al. 1996). A Study on Phen/Fen and Valvular Heart Disease

In a study found in The New England Journal of Medicine, the effects of Fenfluramine and Phentermine on Valvular Heart Disease were studied. The patients were identified during the course of physician evaluations for various clinical problems. They were not chosen or gathered by reviewing data bases, conducting cross-index searches of patient files, or soliciting reports of suspected cases from clinical practices (Connolly et al. 1997).

In May of 1996, a patient, called Patient 1, underwent mitral-valve repair for the treatment of severe mitral regurgitation. At the time, the valve was noted to have a glistening white appearance. This was unexplainable due to the fact that the patient had no history of ergotamine-induced valvular injury, which usually causes the glistening. In July of the same year, Patient 1 was seen by another doctor for severe symptomatic tricuspid regurgitation. Echocardiography confirmed this and showed thickening of the valve leaflets. These same findings were similar to those seen in patients with carcinoid or ergotamine-induced valve disease. A history was obtained, which showed Fenfluramine and Phentermine use for 25 months until one month before the surgery (Connolly et al. 1997).

In January 1997, Patient 7, who had pulmonary hypertension, was evaluated and shown to have thickened aortic-valve leaflets and aortic regurgitation. The same evaluation two years prior had shown no abnormalities. The patient had been taking Fenfluramine and Phentermine for one year before the latest evaluation. In that same month, a doctor called the Mayo Clinic, where the surgery on Patient 1 and the evaluation of Patient 7 had taken place, and asked if they had noticed an association between diet medications and Valvular heart disease. His question stemmed form his noticing that 12 of his own patients with Valvular heart disease had a peculiar valvular morphology. Further study had shown him the exposure of these patients, who were named Patients 2, 3, 6, and 10-18, to Fenfluramine and Phentermine. Valve tissue was obtained from Patients 2 and 3, and slides were prepared (Connolly et al. 1997).

In March 1997 a patient who had received mitral-valve repair the previous year contacted her doctor. Patient 4 told her doctor that she had aortic regurgitation and pulmonary hypertension. Further evaluation of the case showed that the patient had used Phentermine and Fenfluramine for 12 months prior to the surgery. Also in March, tissue taken from Patient 5 was shown to be identical to that of Patients 1, 4, 2, and 3. Patient 5 had also taken Phentermine and Fenfluramine over a period of 11 months (Connolly et al. 1997).

In April of the same year, Patient 8 was evaluated as having multivalvular heart disease and pulmonary hypertension. The same patient had taken the drugs for 6 months. During the time form January 1997 through April 1997 Patients 9 and 19 through 24 were identified with comparable findings (Connolly et al. 1997).

The results said this: "Except for systemic hypertension, all of the patients were thought to be free of cardiovascular disease at the onset of weight-reduction therapy" (Connolly et al. 1997). This lead to the conclusion that the drug Fenfluramine used for weight loss was a cause for the Valvular disease which was discovered in so many of the participants. Conclusions on Clinical Studies

When looking at the studies shown above, the detrimental effects of the phen/fen combination and redux can be seen. In both studies, a significant correlation between the two drugs and the two conditions, Valvular heart disease and Primary Pulmonary Hypertension, is shown. In both cases, the individuals within the studies were compared extensively with each other in order to view patterns among them. Many times this led to new findings. Two critical outcomes were found due to these studies. The first is that the use of Phentermine and Fenfluramine can cause Primary Pulmonary Hypertension. The second is that there is an extremely strong link between the two drugs and Valvular heart disease. The FDA and Phen/Fen

On September 15, 1997 "the Food and Drug Administration, acting on new evidence about significant side-effects associated with Fenfluramine and Dexfenfluramine, has asked the manufacturers to voluntarily withdraw both treatments for obesity from the market" (http://www.fda/gov/cder/news/fenphenpr81597.htm). The FDA claims that the reason for pulling the drugs from the market was due to an abnormal amount of patients with no symptoms who were found to have abnormal echocardiograms. The findings suggest that taking Fenfluramine or Dexfenfluramine are likely to cause problems with heart valves (http://www.fda/gov/cder/news/fenphenpr81597.htm). Conclusions

It is clear looking at research studies conducted by physicians that the drugs Fenfluramine and Phentermine used in combination with each other cause serious if not fatal conditions. Using Dexfenfluramine has very similar effects on the body. What may be startling is the amount of misleading information that can be found on the Internet concerning the use of these three products. According to many of the documents viewed, using these drugs leads to very mild and very few side effects. When viewing the actual research though, the information becomes much more serious. So serious in fact that the FDA banned the sale of the drugs Fenfluramine and Dexfenfluramine due to their extremely dangerous side effects (http://www.fda/gov/cder/news/fenphenpr81597.htm). When looking at these facts it is clear that these drugs are not the answer to successfully losing weight.




  Works Cited

Connolly M.D., Heidi M., Jack L. Crary, M.D., Michael D. McGoon,M.D., Donald

D. Hensrud, M.D., M.P.H., Brooks S. Edwards,M.D., William D. Edwards,

M.D., and Hartzell V. Schaff, M.D. "Valvular Heart Disease Associated

With Fenfluramine-Phentermine." The New England Journal of Medicine 337

(1997): 581-588. Abenhaim, M.D., Lucien, Yola Moride, Ph.D., Francois Brenot,

M.D., Stuart Rich, M.D., Jacques Benichou, M.D., Xavier

Kurz, M.D., Tim Higenbottam, M.D., Celia Oakley, M.D., Emil

Wouters, M.D., Michel Aubier, M.D., Gerald Simonneau, M.D.,

and Bernard Begaud, M.D. "Appetite-Suppressant Drugs and

the Risk of Primary Pulmonary Hypertension." The New

England Journal of Medicine 335 (1996): 609-616.


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