Antidepressant Reboxetine ineffective?

"Reboxetine" ineffective - IQWiG demands publication obligation for studies
The antidepressant „reboxetine“ of the pharmaceutical company Pfizer „is an ineffective and potentially harmful antidepressant. "The authors of the study are Dirk Eyding and Beate Wieseler from the German Institute for Quality and Efficiency in Health Care (IQWiG) in the current issue of the „British Medical Journal“. The worrying: Pfizer has evidently been for 16 long time before various studies that come to the above result. However, the pharmaceutical company has apparently withheld the approval authorities a large part of the investigations deliberately.

„reboxetine“ should help with depression
„reboxetine“ is used as a selective norepinephrine reuptake inhibitor (NARI) in patients with depression. The mechanism of action, unlike most modern antidepressants (selective serotonin reuptake inhibitors), is based on the increase of norepinephrine instead of serotonin. According to the pharmaceutical company Pfizer, the active ingredient is intended to counteract the loss of interest, energy and joie de vivre as well as the concomitant hopelessness, lack of concentration and helplessness in depression patients. With preparations like „Edronax“ and „Solvex“, the the active ingredient „reboxetine“ contain depressive patients are also treated in Germany.

Active ingredient approved in Germany since 1997
The approval has „reboxetine“ in Germany already received in 1997, the assessment
However, only six studies were provided by the regulatory authorities, all of which came to a positive results in the sense of the pharmaceutical company. While many European regulatory authorities approved the drug on the basis of the known studies, the US FDA refused the Pfizer Group in May 2001, however, the market launch for lack of convincing impact evidence (“Lack of compelling evidence of efficacy”). At the beginning of 2002, the Joint Federal Committee (G-BA) commissioned IQWiG with a corresponding benefit assessment of antidepressants in patients with depression, including the active substance „reboxetine“ should be examined again in more detail.

Only six out of 16 studies were submitted to the regulatory authorities
Beate Wieseler, deputy head of the department of drug evaluation in the IQWiG and her team came to the research „reboxetine“ to a large number of previously unpublished studies that were also not available to the regulatory authorities. The authors were able to determine that the active substance had been studied in at least 16 studies with approximately 4,600 participants, whereas the authorities only had the results of six studies with 1,600 patients available. By 2009, the IQWiG should submit its assessment of antidepressants to the G-BA, but despite massive pressure, Pfizer was reluctant to release the remaining studies. For example, the current article by Beate Wieseler and colleagues is still not based on all 16 studies. „Only under massive public pressure“ The examiners were able to persuade the pharmaceutical company to publish at least 13 studies.

Data base increased by 74 percent through subsequent studies
The added data has now been thoroughly investigated by the scientists as part of a meta-analysis, with the subsequent studies increasing the patient base from approximately 1,600 to 3,033 (by 74 percent). "Misleading by concealment is no trivial offense," said Peter Sawicki, at that time head of the testing institute, at the end of 2009 very angry about the actions of Pfizer. Based on current findings, the authors report that the originally provided studies overestimated the effect of reboxetine by 115 percent on placebo and 23 percent over selective serotonin reuptake inhibitors „British Medical Journal“.

Clear result - „reboxetine“ does not help
The clear result of the meta-analysis by the IQWiG experts: „reboxetine“ does not help better against depression than placebo supplements. However, the intake of the drug brings significantly more side effects. So the G-BA has all „reboxetine“ antidepressants already excluded in September 2010 from a reimbursement by the statutory health insurance. Since the authors of the IQWiG see themselves wantonly deceived by the actions of the pharmaceutical company, in the future they demand stricter rules on the obligation to publish all studies produced. Because Pfizer is not an isolated case. The selective publication of positive results studies is one of the most common and most treacherous sources of error in drug approval and later medical use, experts said. Thus, the effect of therapies on certain preparations is often overestimated, as in the case of „reboxetine“, which leads to deficits in the treatment.

Required to publish - about half of all studies remain locked up
The scientists assume that about half of all clinical trials that have begun have not reached the public due to inappropriate results for the clients. According to the authors in the „British Medical Journal“ Therefore, all studies should also be subject to registration in Europe, as was already legally established in the United States in 2007. However, the obligation to publish should not only include studies on medicinal products but also on medical devices and non-medical procedures, according to experts. The obligation to publish in the current draft of the Pharmaceutical Market Restructuring Act (AMNOG) only for selected studies is in their view not sufficient. In addition, according to the IQWiG experts, the results of older studies should also be published accordingly. „We need the results of all studies“, Beate Wieseler explained in a recent press release of the IQWiG. Representatives of the pharmaceutical company Pfizer, on the other hand, expressed themselves rather modestly in their current statements and stated that they were evaluating the rating of Edronax®. However, keep Pfizer „reboxetine“ however, continue to be an appropriate drug for the treatment of major depression depressive disorders. (fp, 14.10.2010)