The Amphetamine Hazard

Amphetamine was scientifically proven to cause severe, incurable heart and lung disorders, and its effectiveness was far from certain at the time of its marketing. That patients got the advice to combine the course of treatment with a hard food diet proves this last fact. In this case the pharmaceutical industry preferred lucrative economic activities above the lives of women and their families.

Since the 1960s the pharmaceutical industry has been producing weight loss medications based on amphetamines such as phentermine, fenfluramine, or the combination of the two (Fen-Phen). The most important producers of these preparations were Servier and Wyeth (the latter bought out the former). Originally the aim of the medications was to treat medically diagnosed cases of obesity, but doctors readily prescribed the products on demand. In addition to the labeled prescription medicines, many self-made amphetamine cocktails and off-label medications were peddled by quacks.

It is known that these weight loss medications increase twentyfold the risk of the rare lung and heart disorder primary pulmonary hypertension (PPH) and other cardiovascular and lung disorders. The symptoms of PPH include permanent breathing problems, fatigue, and dizziness. Apart from heart-lung transplantation, there is no cure. At present, the symptoms can only be controlled by wearing an apparatus that supplies medication directly into the heart. Side effects of those medications include swollen legs, headache, sickness, and diarrhea. Governmental response was very slow in coming. After long discussion between governments and industry, the products have finally been withdrawn.

The Food and Drug Administration in the United States, as well as the European Medicines Agency (EMEA), first decided in 1996 to add the risks in the package insert and to limit the occasions for prescription. The pharmaceutical industry could avoid having any reference to causation in the insert. In 1998 the industry decided on its own to withdraw the older amphetamine-based weight loss products. Only in 2000 did the European Commission officially remove the license to produce amphetamine-based weight loss drugs. In the meantime a new generation of weight loss drugs has been marketed. The first such product, sibutramide, marketed as Meridia, is also an amphetamine-based drug working on the brain. In 2002 it was linked to 33 deaths in Europe and the United States, one of the reasons why the Italian government forbade the distribution. The other product, orlistat (marketed as Xenical), is not amphetamine-based but acts on the digestion mechanism. The results of the clinical tests do not sound very promising. Nevertheless, the EMEA considered the benefit-to-risk assessment positive.

During the 1990s and early 2000s the market for surgical procedures to reduce stomach capacity and food uptake has exploded. The risks are high, while the effectiveness is not proven in all cases. The market for slimming products and methods is insatiable. The responsibility in this case is not referable to the pharmaceutical industry alone. The industry is responsible because it could have been alerted by the dangers shown by studies published in medical journals such as the New England Journal of Medicine and the Lancet. Instead of being alarmed, they paid scientists to write research reports in favor of their products. Doctors are responsible because they were strongly advised to prescribe only for clinical obesity, but many doctors prescribed off-label drugs and self-made cocktails. Governments are responsible because authorities did not react firmly when they became aware of the dangers. They took measures in mutual agreement with the concerned companies. This conflict was resolved differently in different countries. After the refusal of Servier to settle to case, the company was ordered by the French civil court of Nanterre to pay damage to the victims. This ruling was affirmed on appeal by the company, and more victims brought their cases before a court. In the United States and Canada the pharmaceutical industry paid billions of dollars for the settlement of individual cases and class-action suits. The companies refuse to admit causality between the damage and their products. In Belgium, one patient who participated in a clinical test of the medicine and got PPH won her case against the hospital where the medicine was tested. This relative success in conflict resolution is partially related to the organization of victims in self-help groups and the support they get from doctors and lawyers. Victims who are members of a patients’ association are stuck in a difficult position concerning conflict resolution because these organizations get support from the pharmaceutical industry. As a result, victims in patients’ associations risk loss of this financial support if they press for conflict resolution with a pharmaceutical company. Companies are not likely to continue supporting associations that take legal actions against them.