How that came to be is a story in itself, but the basics are that in the 1950s scientists discovered, serendipitously, that a drug called iproniazid seemed to help some people with depression. ❋ Unknown (2010)
In the early 1950s, a new drug, a nicotine derivative, called iproniazid had been shown to be effective in treating tuberculosis, and studies to further validate its usefulness were being conducted in Europe. ❋ Unknown (2010)
Nathan Kline, an American psychiatrist, upon learning about the odd effect, saw the potential, and conducted a clinical trial that quickly established iproniazid as the very first anti-depressant. ❋ Unknown (2010)
Despite a spirited defense by Senator Everett Dirksen, who accused his colleague Estes Kefauver of “headline hunting” when he convened hearings on these questions, Roche voluntarily withdrew iproniazid from the market in 1961, the pharmaceutical house by then no doubt ruing the day that it had listened to the likes of Nate Kline. ❋ Gary Greenberg (2010)
Instead, by the end of 1957 Kline was urging doctors to move ahead with a project to determine whether drugs like iproniazid “could improve ordinary performance.” ❋ Gary Greenberg (2010)
If iproniazid was a monoamine oxidase inhibitor MAOI, and if at least one monoamine—serotonin—had been implicated in mental illness, then it stood to reason that iproniazid worked because it stopped the destruction of serotonin, thus increasing its presence in the brain. ❋ Gary Greenberg (2010)
Leading the charge were scientists wielding their knowledge that iproniazid blocked the action of monoamine oxidase MAO, an enzyme that broke down a group of brain chemicals that included serotonin, known collectively as monoamines. ❋ Gary Greenberg (2010)
In the next year, Roche, which had all but abandoned iproniazid as an antitubercular, sold the drug to four hundred thousand presumably happy, or at least less unhappy, customers. ❋ Gary Greenberg (2010)
In 1956, Kline heard that scientists had given iproniazid along with reserpine to lab animals, which, far from being sedated, had become hyperactive. ❋ Gary Greenberg (2010)
The drug—iproniazid, or as Hoffman–La Roche called it, Marsilid—was having some remarkable effects. ❋ Gary Greenberg (2010)
In 1965, he reviewed all the evidence—the reserpine research, the clinical trials with drugs like imipramine and iproniazid, the studies showing evidence of increased catecholamines in the blood and urine of people taking antidepressants, the discoveries of enzyme and reuptake inhibition—and concluded, “There is good evidence to support the thesis that the antidepressant effects of both the monoamine oxidase inhibitors and the imipramine-like drugs are mediated through the catecholamines.” ❋ Gary Greenberg (2010)
When the depressed patients seemed to be getting better, Kline arranged to testify to Congress on the subject of iproniazid and to have his work published in the Congressional Record—a move that at once avoided peer review and guaranteed publicity. ❋ Gary Greenberg (2010)
Kline was in a good position to mount his campaign for iproniazid. ❋ Gary Greenberg (2010)
The problems began in April 1958, when Frances Simpson, a fifty-five-year-old San Franciscan, met an untimely demise, which the coroner blamed on liver failure due to iproniazid use. ❋ Gary Greenberg (2010)
The reserpine experiments, the ones that showed less serotonin activity in the brains of animals that had suffered a reserpine-induced “depression,” gave credence to this emerging hypothesis about how iproniazid worked, and, in the bargain, to the serotonin theory of mental illness. ❋ Gary Greenberg (2010)
The bad news, however, was that the new article—“CITY RESTRICTS SALE OF ENERGIZING DRUGS”—was mostly about the forty health-department agents who were at that very moment fanning out across the city to impound supplies of iproniazid. ❋ Gary Greenberg (2010)
MAOI drugs like iproniazid, on the other hand, countered the reserpine effect and raised levels of norepinephrine. ❋ Gary Greenberg (2010)
The resulting therapeutic chaos alarmed Estes Kefauver and his Anti-Trust and Monopoly Subcommittee—the same body that listened to testimony about iproniazid and other “quick pills.” ❋ Gary Greenberg (2010)
Within a few years, reports of jaundice and other liver-related ailments in iproniazid users began to pour in. ❋ Gary Greenberg (2010)
Even as iproniazid was crashing and burning, imipramine and a host of related compounds were on a slow and steady ascent. ❋ Gary Greenberg (2010)
