A resident of Lanzarote reports suffering from depression after ingesting Agreal, a drug intended to mitigate the symptoms of menopause

When the cure is worse than the disease

The morning is hot in Arrecife. Through its streets, you can hear voices of people strolling, laughter of children who have already left school, and traffic roaring in rush hour. But in Mari's house (fictitious name under which...

June 16 2008 (07:19 WEST)
When the cure is worse than the disease
When the cure is worse than the disease

The morning is hot in Arrecife. Through its streets, you can hear voices of people strolling, laughter of children who have already left school, and traffic roaring in rush hour. But in Mari's house (fictitious name under which she prefers to hide) the atmosphere is different. With the curtains drawn, with hardly any light, and in the midst of a sepulchral silence, this fifty-five-year-old woman confesses to us, lowering her gaze "I have no life". Six years ago, her gynecologist prescribed her the drug Agreal, manufactured by the company Sanofis-Aventis, to reduce the symptoms caused by menopause, "but since I started taking the pills I fell into a deep depression". "I went to the family doctor, who prescribed antidepressants. He didn't attribute it to the other drug I was taking either."

Months passed and she continued with her daily dose of one pill and each day with less encouragement to do anything until one day her son went to the pharmacy to buy her Agreal and found that it had been withdrawn from the market. The Spanish Agency for Medicines and Health Products, through the Committee for Safety of Medicines for Human Use, had suspended its commercialization in September 2005 because "its benefit-risk balance was unfavorable for the treatment of hot flashes and manifestations (?) of menopause". The agency recommended that the withdrawal of treatment be gradual and carried out with rigorous medical monitoring. But Mari was unaware of all this. She simply stopped taking it, and the symptoms continued until today. "I've been like this for six years and I'm not getting better. I wasn't like this before. I used to get dressed up, put on makeup and now nothing, I don't feel like doing anything."

An arduous judicial process

One day, her son saw on television that a group of affected women had filed lawsuits against the company and encouraged his mother to also take legal action. At the moment, her trial remains open in the Commercial Court No. 6 of Barcelona, awaiting the sentence. Along with Mari, another 69 people have filed lawsuits, although the prospects are not very encouraging for them. Of the total of 402 lawsuits that the affected women have filed against the company since 2005, only 3 have been admitted, which Sanofis has appealed. "The justice system has already ruled with sufficient forcefulness in this regard, dismissing practically all of the lawsuits, finding no scientific or medical link between the symptoms presented by these patients and the treatment with this drug. The experts participating in the civil trials state categorically that it is physically and medically impossible for Agreal, by itself, to produce depressive disorders or withdrawal syndrome," says Gloria Pujol, spokesperson for the company. However, the Provincial Court of Barcelona ruled against Sanofis in November 2007, considering that, in view of the evidence presented by the affected women, "there is a causal relationship between the ingestion of the drug and the effects produced in the aforementioned cases."

In addition, according to the lawyer representing the majority of the affected women, Fernando Osuna, the drug's leaflet did not refer to the adverse reactions that it later caused in the patients. "In other countries, the leaflet did provide correct information," he adds. Only in this does the lawyer agree with the company. "In 2002, Sanofi-Aventis submitted a request to the competent authorities to expand the information on the Agreal leaflet, but did not receive an official response, so the leaflet remained as it was. In other countries, this authorization was requested and obtained," indicates the company's spokesperson.

Lime and sand

The Ministry of Health itself, through the General Directorate of Pharmacy, agreed, together with the association of affected women that existed at that time (today there are two), in June 2006, to create a special commission to evaluate the symptoms of the affected women. The Commission was composed of professionals from the Spanish Society of Psychiatry, Neurology, Family and Community Medicine, Clinical Pharmacology and the Spanish Association for the Study of Menopause, and concluded that the symptoms were "very similar to those commonly found in daily clinical practice, in women between 40 and 60 years of age". In addition, the report, published in February 2007, pointed out that the fact that a good number of patients continued to present symptoms after withdrawing the drug had no "biological explanation based on the pharmacological data of the product." Therefore, the report signed by the director of the Spanish Agency for Medicines and Health Products, Cristina Avendaño, concluded that "the problems referred to by the patients are common and can be addressed through the usual channels of the National Health System."

A report that dashed the hopes of many of the affected women. However, months later, they saw a small ray of light open up: the European Medicines Agency decided to suspend the commercialization of the product in France, Belgium, Italy, Luxembourg and Portugal. "The risks associated with the use of veralipride (component of Agreal) in the treatment of hot flashes associated with menopause outweigh the limited beneficial effects," the Agency explains in a statement. In addition, it recognizes that cases such as Parkinson's syndrome, depression, anxiety and withdrawal syndrome have been reported with veralipride treatment. Thus, the Standing Committee on Medicines for Human Use recommended the withdrawal of all marketing authorizations for products containing veralipride throughout Europe.

The lawyer for the affected women welcomed the news with optimism. Despite the fact that almost all of their lawsuits have been dismissed, Fernando Osuna is hopeful. "Right now we have the support of other law firms, so we can afford a larger team of medical professionals to testify in the trial, supporting the arguments of the affected women," explains Fernando Osuna.

Who is responsible?

"What we are asking for is that the justice system recognize that the drug is defective and that it causes damage. Of the three complaints that have been upheld, the compensation is meager, between 5,000 and 7,000 euros, compared to the 60,000 that we were asking for," explains the lawyer. A compensation that the company has not yet paid because the three complaints that have been upheld are being appealed to higher courts. However, this does not interest Mari. Tired, pessimistic, she confesses: "I don't expect anything from the sentences, nothing." "This cannot be compensated with money. Just paying for the doctors I need would be enough, paying for the psychologist and curing what they have done to me, but nobody can cure that anymore," she adds resignedly. Because she right now, despite having been diagnosed with depression by her family doctor, cannot afford the services of a psychologist. "I am separated and in my state, I cannot work. One day I am well, another day bad... I live with the help that my ex-husband gives me," she says.

In fact, Mari says that she had to borrow money to be able to testify in the trial that is being held in the Commercial Court number 6 of Barcelona. "It was horrible. The people from the company treated you with contempt, as if you were lying. I would never go through something like that again," she declares emphatically. The company defends itself by arguing that it has attended to all the queries it has received from the affected women and healthcare personnel. Although Mari acknowledges that she has not contacted Sanofis-Aventis, she complains that the company, at no time during the trial, showed any interest in how the affected women were doing.

"It's as if there is a dark hand behind this whole matter," explains Fernando Osuna. He cannot explain how the justice system has been able to dismiss, jointly, two cases of 90 and 127 lawsuits each. The law firm has appealed them to the Provincial Court of Barcelona. "It is clear that the responsibility lies with Sanofis but the State, through the body that approved the commercialization of the product, would also have its grain of guilt," says Osuna convinced. However, fighting against the State becomes very costly "which is prolonged in time, so we opted to take legal action against Sanofis." Despite the fact that, until now, the company has won practically all of the trials, Osuna's law firm plans to file more lawsuits, about four hundred in two litigations, but this time in Madrid. A tough judicial battle from which Mari feels alienated. "They have taken away my desire to live, and nobody is going to give that back to me," she confesses dejectedly.

WHAT IS AGREAL?

Agreal is a drug composed of Veralipride and was indicated to treat hot flashes and psychofunctional manifestations of confirmed menopause. In Italy, the drug was marketed under the name Agradil. It was first authorized in 1979 and was sold, with a medical prescription, in Belgium, France, Portugal, Italy, Luxembourg and Spain.

THE LONG JOURNEY OF THE CONTROVERSIAL PILLS

- 1983: The commercialization of Agreal in Spain is approved.

- May 2005: The Spanish Agency for Medicines announces the suspension of the commercialization of Agreal.

- September 2005: From this date, Agreal cannot be sold in any pharmacy.

- February 2007: The Ministry of Health issues a report in which it disassociates the symptoms of the affected women with the ingestion of Agreal.

- June 2007: The Court of First Instance No. 13 of Barcelona dismisses 130 lawsuits from affected women, who have appealed the sentence to the Provincial Court.

- July 2007: The European Medicines Agency suspends the commercialization of Agreal.

- November 2007: The Provincial Court of Barcelona upholds and confirms three lawsuits against the effects of the drug, the only ones out of 402. The company appeals the sentence to the Supreme Court.

- July-August 2008: The Commercial Court No. 6 of Barcelona will issue a sentence regarding the last 70 lawsuits filed.

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