A Short History of Medication in the West: Antidepressants

Let’s take a trip back to the 1950’s. We’re in New York sitting in front of two chemists who think they’ve synthesized a new drug to treat Tuberculosis. They’re not wrong, but what they’ve found is also a wellspring that will fuel pharmacological developments beyond the turn of the century.

In 1952, Herbert Fox and John Gibas developed iproniazid, an anti-tubercular drug which improved patients’ mood, ability to sleep, and appetite in clinical trials. With further testing, it was ready to enter the US market as Marsilid in 1958. Iproniazid took effect by inhibiting MAO, an enzyme responsible for the breakdown of the neurotransmitters serotonin and norepinephrine in the brain. Several years after its introduction, there were cases of jaundice that cropped up in those taking the drug, along with concerns of increased heart rate and hypertension; Marsilid was seen exiting the market as fast as it came.

Meanwhile, halfway across the world, the Geigy corporation in Switzerland was developing imipramine, a tricyclic antidepressant.  Tricyclics have a dual function: blocking neurotransmitter receptors and inhibiting the reuptake transporters that recover them from the synapse.  The end result is an increase of serotonin and norepinephrine in the synapses between neurons, with mood bolstering effects mirroring those of Marsilid.

At this point we’ll stop and acquaint ourselves with the monoamine theory of depression. In 1965, an American psychiatrist by the name of Joseph Schildkraut wrote an article reviewing pharmacological research that trailed the development of the then-novel antidepressant. Schildkraut proposed that depression was linked to a deficiency of a class of neurotransmitters known as catecholamines, which includes norepinephrine.

While the basis of this theory has fallen into criticism under recent years, it played a significant role in driving future antidepressant development. Close on his heels, Alec Coppen released a review in 1967 proposing a different theory that linked depression to deficiencies in serotonin. And so it is of little surprise that in 1974, a report was published on fluoxetine, a new antidepressant that worked by inhibiting the reuptake of serotonin in neurons. Known as Prozac on release, this drug is one of several Selective Serotonin Reuptake Inhibitors (SSRIs) released in the final quarter of the 20^th century. From its conception to the turn of the millennium, several other SSRIs were developed, tested, and released. Sertraline, citalopram, paroxetine, and escitalopram are among these, known by the brand as Zoloft, Celexa, Paxil, and Lexapro.

We are now in an age where SSRIs are by far the most popular antidepressants used. And just like their predecessors, taking these types of medications can come with a cost. People may experience any range of dizziness, nausea, insomnia, decreased sexual function, and what some describe as emotional blunting. Whether it is worthwhile is something you can only experience firsthand.

Addendum: To those who find themselves piqued, I would recommend reading a history of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM currently offers psychiatrists a standardized method for diagnosing various mental disorders; however, it was not always so. Its story provides a much needed social context for the development of the aforementioned drugs, and the changing role of psychiatrists and their operating methods.