Requesting a history of diphenhydramine! I read somewhere that it was the first discovered SSRI, but can’t remember where.
This will be the history of diphenhydramine as an SSRI and the drugs surrounding it. The history of diphenhydramine as a whole is longer than my standard post length and I would want to do it justice!
It was technically the first available SSRI (becoming available by prescription in 1946), but it's SSRI activity was not discovered until the 1960s, after the SSRI activity of brompheniramine (available 1955) was discovered.
Brompheniramine was the first antihistamine to be studied as an antidepressant, as it was noted to have antidepressant properties strong enough to be usable. Out of this research came the antidepressant drug zimelidine, which went to market in 1982. Two years later, this drug would be withdrawn due to reports of Guillain-Barre syndrome.
Diphenhydramine does not have antidepressant effects strong enough to be usable, but it does weakly inhibit serotonin reuptake. Out of research into the antidepressant potential of diphenhydramine, the antidepressant fluoxetine (Prozac) was created. Fluoxetine went on the market in 1986 and is the 25th most commonly prescribed drug in the US today.
