WHAT IS THALIDOMIDE?

A SHORT HISTORY OF THALIDOMIDE

Thalidomide is a sedative drug discovered at the end of the 50s, which caused a worldwide tragedy. The drug has been prescribed to many pregnant women in order to relieve pregnancy nausea. It was later found that thalidomide caused irreversible damages to the fetus and thousands of children were born with severe congenital malformations. Many of them did not survive more than a few days after they were born. For a more complete historic of the Canadian tragedy, click here.

The chemical formula for thalidomide is C13H10N2O4.  It is also known under the scientific more scientific name α-(N-Phthalimido)glutarimide.

Thalidomide was first synthesized in 1954 in Western Germany by the firm Chemie Grünenthal, who found out that thalidomide had interesting sedative effects. Thalidomide appeared as a promising alternative to barbiturates that were then used as sedatives, because it didn’t seem to be toxic nor have any side effects. An overdose would only cause deep sleep, as opposed to barbiturates which could cause death if taken in excessive quantity.

thalidomide molecule

Thalidomide was marketed in 1956 by Chemie Grünenthal in Western Germany, first as an anti-flu, then in 1957, as an hypnotic drug. It was then available without prescription. In April 1958, thalidomide was marketed in the United Kingdom by Distillers Company. Several countries followed suit and thalidomide was put into circulation under many different brands. Overall, thalidomide was sold under about 40 different names around the world, principally in Western countries and in Japan. Important advertising campaigns were led by its fabricants, starting with Chemie Grünenthal and Distillers Company. Thalidomide was described as a miracle drug. Thousands of samples were distributed to doctors, who were encouraged to prescribe it to pregnant women in order to alleviate pregnancy nausea. Everyone was told that this drug represented no risk at all for pregnant women.

The following excerpt, from the website of the documentary “NO Limits” addressing the thalidomide tragedy, describes particularly well how negligent Grünenthal was regarding the safety of thalidomide:


“What the public did not know is that Grünenthal had no reliable evidence to back up its claims that the drug was safe. They also ignored the increasing number of reports coming in about harmful side-effects as the drug was being used. In fact, starting in 1959 Grünenthal was flooded with complaints from doctors about mild to severe and sometimes permanent nerve damage, especially by elderly people who had used the drug as a sleeping aid.

[…]

The company was equally dismissive of concerns related to deformed babies. The drug was widely promoted as an anti-nausea drug for pregnant women experiencing morning sickness. When the company was confronted with reports on malformed babies and suggestions that the malformations could be possibly linked to Thalidomide, they didn’t react. Instead of taking all those reports seriously Grünenthal responded with measures to keep the drug on the market.”


As early as 1960, unsuspected side effects on the nervous system started to be attributed to thalidomide by some doctors. The first concerns about teratogenic hazards were raised in Western Germany in October 1961. We had to wait more than six weeks after that for the drug to be withdrawn from the british and german markets, at the end of November and in early December. But it was already too late: thousands of babies around the world would be born with severe malformations. Other authorities were even slower to withdraw thalidomide from the market, so that in some countries, it was available until the end of 1963. 

It is hard to tell with precision how many thalidomide victims there is, because a lot of babies were dead before birth, stillborn or died soon after birth due to the severity of their malformations. Not all of these births were registered in proper form, especially considering that several thalidomiders infants are believed to have been infanticide victims. It is estimated that 15,000 children were born worldwide with malformations attributable to thalidomide. The victims also include the families of all these children, whose life were severely impacted by this tragedy.

Not so long after that, new therapeutical effects were discovered to thalidomide, for treating or alleviating leprosy, systemic lupus erythematosus and some cancers, among others. The drug is currently available in many countries for these uses. To know more about the actual uses of thalidomide, click here.

MAIN HAZARDS AND SIDE EFFECTS LINKED TO THALIDOMIDE

Peripheral neuritis

Peripheral neuritis is a type of nerve injury that may happen when one takes thalidomide. Peripheral neuritis can manifest anywhere in the body. It begins with a tingling sensation in hands and feet, followed by numbness and sensations of cold. The numbness expands and is followed by severe muscular cramps, a weakness of the limbs and a lack of coordination. Some of these symptoms can improve or disappear, but in some cases, the damages are irreversible.

Patients on thalidomide are recommended to cease treatment immediately and contact their doctor if they experience nerve injury symptoms such as: a burning sensation, numbness or pins and needles in the arms, hand, legs or feet.

Fetal impairment

Here is a non-exhaustive list of the impacts that thalidomide may have on the fetus when taken by pregnant women: bilateral limb atrophy (legs, arms or both) – a condition known as phocomelia, bilateral limb absence (amelia), missing fingers or toes, palmature of the fingers or toes, extra fingers or toes, total or partial hearing loss, partial or total vision loss, paralysis (usually facial muscles), malformation of the digestive tube, malformation of the duodenum (most of the time lethal, before or not long after birth), malformation or absence of the anus, vital organs injury (most of the time lethal, before or not long after birth), death.
Because of the aforementioned devastating effects, thalidomide is strictly contraindicated on pregant women or women and women at risk of becoming pregnant.

You can find more detailed information about congenital malformations linked to thalidomide in the Congenital malformations section of our website.

For more information on the hazards and side effects of the drug thalidomide, visit Health Canada’s page on THALOMID.

 
Baby with phocomelia at the four limbs.

THE MECHANISM OF THALIDOMIDE

As of today, the mechanism by which thalidomide cause birth defects is not confirmed. There are, however, a few hypotheses regarding its effects on the organism, which have been published by researchers in various journals. As these are articles of a scientific nature whose writing style is rather technical, you will find these references in the Publications & Links section of our website, under “Academic and Scientific Publications”.

 

 

https://thalidomide.ca/en/what-is-thalidomide/