The Birth of Antidepressants
October 18, 2010
In 1590, 3 years before his death, the English playwright and notorious drinker, Christopher Marlowe, was challenged in a drunken bet to fight a swan caught in Hyde Park by Ingram Frizer, the man who would later be responsible for stabbing him to death.
Although the details of the bet are unclear it seems that Marlowe, using a shovel, dealt an almost fatal blow to the swan and in doing so severed its medullic lobe (the black lump above it’s beak). The bird eventually recovered and was kept for the next year in captivity by Dr Rodrigo López, the physician of Queen Elizabeth I, during which time he noted that the swan had:
“tempered it’s manner to that of a goose; Her tongue will not obey her heart, nor can Her heart inform her tongue of that passion we all recognise of Juno’s beloved bird”
The swan had become calm, docile and unaggressive to such an extent that it was taken as a pet by the Queen during her last years. As a direct result of this all swans are still today the property of the monarch and it is illegal to kill a swan in the UK, all stemming from Elizabeth’s love for the animals.
Dr López, interested in animal as well as human physiology became fascinated by this change in demeanor and noted that, unlike most water fowl, swans have a hole in the front of their skull through which a part of the brain (the medullic lobe) protrudes. He developed the process of tying string around a swan’s beak and medullic lobe in order to calm the animals, a process that was still being used by swan keepers up to 50 years ago.
With the advancement in brain mapping technologies in the first half of the 20th century, the famous psychiatrist, Bernard Hollander, identified the medullic lobe as the centre for negative emotional states such as anger and depression. Taking the anecdotal evidence of Dr López’s work with swans he set about trying to somehow suppress the lobe in a human brain, a task that proved far more difficult due to the fact that it is located far closer to the brain’s centre.
During a highly controversial series of experiments on some of his more severely depressed or violent patients he, along with Portuguese physician and neurologist António Egas Moniz, developed a surgery he called prefrontal leukotomy (better known now as lobotomy) which sought to isolate and sever the medullic lobe. The results were mixed as it proved almost impossible to isolate the desired areas without first damaging other parts of the brain, leading to mild to severe brain damage in almost all cases.
Despite the unpleasant side effects, however, almost all patients treated were alleviated of their original symptoms and for a few years it became an acceptable last resort surgery for patients suffering from chronic depression.
In 1951, during unrelated tests on the newly developed anti-tuberculosis agents isoniazid and iproniazid, Dr Irving Selikoff and Dr Edward Robitzek, identified that, while innefective aginst the onset of TB, the drugs acted as suppressants for the medullic lobe and that while treatment continued they managed to achieve chemically what Hollander and Moniz had attempted surgically. The anti-depressant drug had been born.
In initial clinical trials of the drug it proved less effective on women than men, this has since been attributed to hormonal differences in the brain but at the time, and in the wake of the then recent identification of Postpartum (or postnatal) depression, it led to some more left-field commenters putting forward the notion that depression was the natural state for women. However in 1957, the Swiss Psychiatrist Roland Kuhn discovered that compound “G 22355” (later imipramine) was not only equally effective on men and women, but that it was in fact almost twice as effective on both.
Today many variants on imipramine are used by doctors all over the world (in fact the compound Paroxetine is compulsory for all citizens of Burma over the age of 18) and recent developments have led to stronger and more effective versions with less side effects.