Controversial disease dropped from Prozac product informationBMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7436.365 (Published 12 February 2004) Cite this as: BMJ 2004;328:365
The drug manufacturer Lilly has been forced to drop one of the disorders it had previously listed for its antidepressant drug fluoxetine (Prozac), following a finding by the European drug regulator that the condition was not a well-established disease entity.
Some health researchers welcomed the regulator's decision, saying premenstrual dysphoric disorder (PMDD), which was only recently described, was an invented illness and a strong example of the medicalisation of ordinary life.
“I think it's a wonderful decision” says Paula Caplan, a psychologist adjunct and professor at Brown University, Rhode Island. “This kind of scrutiny of the science or lack of science behind trials of drugs is all too rare and it is to be praised.”
Lilly informed health professionals in a letter in December that it had removed premenstrual dysphoric disorder as an indication for fluoxetine, citing a ruling by the European drug regulator earlier in the year.
In June 2003, as part of European harmonisation of product information, the Committee for Proprietary Medicinal Products found that “PMDD is not a well-established disease entity across Europe.” It said that the disorder was not listed in the international classification of diseases and was listed only as a research diagnosis in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders.
The committee strongly criticised two key trials of fluoxetine for premenstrual dysphoric disorder, noting that in one study almost half of the participants dropped out and that in the other little attempt was made to distinguish between mild and severe health problems. “There was considerable concern that women with less severe premenstrual symptoms might erroneously receive a diagnosis of PMDD resulting in widespread inappropriate short and long term use of fluoxetine,” wrote the committee.
Fluoxetine was first approved for premenstrual dysphoric disorder by the US Food and Drug Administration in 2000, after an influential 1998 “round table discussion” of experts supported by Lilly and attended by at least four Lilly representatives. The disorder was characterised by anger, irritability, and tension triggered by the menstrual cycle.
An aggressive promotional campaign quickly followed, including television advertisements featuring a frustrated woman with a shopping trolley outside a shop and accompanied by the line, “Think its PMS [premenstrual syndrome]? It could be PMDD.” The campaign was criticised by some women's groups and was found by the Food and Drug Administration to be unbalanced and misleading because it “broadens the indication” and played down side effects (http://www.fda.gov/cder/warn/nov2000/dd9523.pdf).
In 2001, based on the work of Caplan and others, the Society for Menstrual Cycle Research called on the administration to overturn its approval of fluoxetine for the disorder, asserting that the condition did not exist and widespread use of the drug for menstrual problems could mask other causes of women's suffering. Instead the regulator has gone on to approve a number of other antidepressants for the disorder.
A spokesperson for Lilly said company officials understood the European regulator's decision, but thought it “unfortunate”.