It all started so promisingly, when drugs like Prozac first came on the market in the 1980s. Here at last, we were told, was a new class of antidepressants that would transform the world of psychiatry.

Out would go the old ‘dirty’ psychiatric drugs of the 1950s, and in would come a set of drugs honed by science to target the biochemical core of depression in the brain.

These new drugs had a very scientific-sounding name—‘selective serotonin reuptake inhibitors’—which neatly morphed into the catchy acronym ‘SSRIs’. They are among the most successfully marketed drugs in history, so much so that the brand leader Prozac is almost a synonym for antidepressants, just like Hoover is for vacuum cleaners.

But now, some two decades later, the world of psychiatry has finally discovered it has been largely taken for a ride with SSRIs, by both drug companies and lax regulators.

‘Miracle’ science
In the brain, messages are passed between brain cells (neurones) across a tiny gap called a ‘synapse’. This gap is filled with chemicals, which have the job of controlling the communication between brain cells, transmitting information from one neurone to the other. Hence, these chemicals are called ‘neurotransmitters’. When one neurone communicates with its neighbour, it floods the synapse with a cocktail of neurotransmitters, one of which is serotonin.

By the 1970s, it had been discovered that some prescription drugs can cause depression as a side-effect, a problem traced to low brain levels of serotonin. It was then argued that, if a way could be found to increase serotonin in the brain, it would reduce depression.

It’s already known that the brain naturally conserves neurotransmitters by allowing the transmitting cell to reabsorb them from the synapse (a process that is called reuptake). So, if a way can be found to stop (or inhibit) this reuptake, the synapse would remain constantly bathed in neurotransmitters. But only one neurotransmitter—serotonin—is involved in depression, which means that only serotonin needs to be selectively isolated from the rest of the neurotransmitter cocktail.

So, in the mid-1970s, the pharmaceutical companies set themselves the task of finding a drug that would select out serotonin, and inhibit its reabsorption by the transmitting neurones. Ten years later, the family of SSRIs was created.

The first SSRI appeared in the mid-1980s from the Swedish pharma company Astra. The drug’s chemical name was zimelidine, but it was quickly withdrawn from the market when patients developed Guillain–Barré syndrome (a serious auto-immune condition involving damage to the peripheral nerves). Soon after-wards, a second SSRI, a French drug called indalpine, was also stopped after it was found to damage blood cells.

These straws in the wind didn’t deter other drug companies, however —although the SSRI’s hoped-for lack of side-effects had been intended to be a major part of their sales pitch.

The first SSRI to come to market was fluvoxamine (see box, page 8), but its manufacturer Solvay Pharmaceutical, based in Georgia, lacked marketing clout, making its launch a bit of a damp squib.

It took the marketing power wielded by the giant US (and international) drug company Eli Lilly to collar most of the SSRI public relations when it launched fluoxetine in 1987, under the memorable trade-name Prozac. Newspapers were quick to swallow the company’s sales pitch, with headlines describing Prozac as a “happiness pill”. Even normally cynical journalists described Prozac as a valuable, quick, emotional fix, and a panacea for the stresses of the 20th century.