The flood of negative reports about adverse effects of the anti-smoking drug buproprion (ZYBAN, see a-t 2001; 32: 94) that surfaced in Great Britain - 7,500 reports, including 58 deaths (1) until April 2002 - forced the European Agency for the Evaluation of Medicinal Products (EMEA) to reevaluate the benefits versus the potential damages of this drug once again (2). By mid-2001, the manufacturer had already received reports about 245 deaths worldwide in connection with buproprion (3). Since ad hoc postmarketing surveillance reports comprise only about 2% of the total number of adverse side effects (4), potentially 12,000 cases of death could have occurred. We had repeatedly warned about prescribing this drug (e.g. a-t 2001; 32: 56 and 64). Buproprion has no effect in treating depressions (in the USA: WELLBUTRIN). Now, research concentrates on the drug's potential as an appetite suppressant - as treatment for obesity, since loss of appetite has been reported as an adverse side effect in about 3% of cases. A pilot study revealed that a daily dose of 400 mg reduces overweight better than 300 mg per day (5). The researchers seem to neglect the fact that just a few months ago, the maximum dosage for the treatment of smokers was limited EU-wide to 150 mg twice a day, due to the dosage-dependent potential of causing convulsive seizures.
Topiramat (TOPOMAX) is another drug that is researched for the same marketing indication. This drug is indicated as an adjunctive therapy for patients with partial onset seizures. We consider topiramat a drug of second choice because it can cause severe adverse effects of the central nervous system such as difficulty to concentrate and memory impairment, and treatment had to be stopped repeatedly due to dosage-dependent adverse effects (in 28% of clinical studies). Furthermore, it is a potential carcinogenic and teratogenic substance. Since patients lost weight while taking this drug, it occurred to the manufacturer Johnson & Johnson to turn the side effect into an indication. However, testing it for its potential to treat obesity had to be stopped due to the not entirely unexpected severe adverse effects. Now, the company intends to continue experimenting with a supposedly improved 'retard' version of the drug (6). The basis on which ethics committees approve the testing of such risky drugs for indications that can be treated without drugs, remains a mystery to us.
We find it alarming that certain companies seem to weigh revenue expectations for an anti-obesity drug well ahead of the drug's benefit-harm relationship. Medicines that are poorly-tolerated will be labeled with indications, which should not be treated with drugs. In addition, there are a number of other trials going on attempting to expand the marketing profile of topiramat. Among them are studies for its use as a preventive treatment for migraines, for use in the manic-depressive symptom complex, and even for treatment of diabetic nephropathy, although three pilot studies did not reveal any advantageous effects over the use of a placebo (7).
"Ideas for a Healthy Life" is the slogan under which Janssen-Cilag advertises topiramat in Germany as a supposedly "well-tolerated" anti-epileptic drug (8). The "idea" seems to concentrate more on expanding marketing share. This is done systematically: Since public authorities have withdrawn from planning and financing clinical research, companies increasingly began to promote studies that pursue clear marketing goals in favour of therapeutic needs (9). Any kind of state control is missing. Nowadays, a new drug study that is performed without the participation of private companies has become an exception. The quality of state controlled studies, however, can be appreciated in one of the latest examples of comparing different types of interferon for the treatment of multiple sclerosis, a study whose design was obviously not influenced by company interests but rather by the current level of knowledge.