Olga Khazan: What were the options for depression before antidepressants came along?

Lauren Slater: You could be treated with morphine, which was legal for a long, long time. The use of the barbiturates became legal in 1904, and you could be treated with those. There were various tonics and brews that people made out of leaves. They would brew up teas. You could be treated with lithium. Lithium baths were pretty popular for a while.

Then the other thing was that you just didn’t treat it at all and you waited it out. Usually, depression remits, but sometimes it can take too long a time.

Khazan: Why was Prozac so different from the antidepressants that came before it?

Slater: The tricyclics, which came before Prozac, were thought only to be relevant for a population of very ill people, deeply depressed people, whereas Prozac was marketed right from the beginning to the general public. People used it to treat dysthymia, which is a more mild kind of depression. Prozac was like every man’s drug.

That said, when you look at the studies, there really is no difference in the efficacy rate of Prozac versus the tricyclics. The tricyclics worked on two-thirds of the people who try them. Prozac works on two-thirds of the people who try it.

Prozac was marketed as a site-specific drug. It was supposedly able to home in on a tiny target in the brain: It was a selective serotonin reuptake inhibitor, whereas the older drugs cast a wide net over the brain. But it’s almost preposterous to think that you can target just the serotonin system in the brain, because the serotonin system is linked to the dopamine system, which is linked to the norepinephrine system, which is linked to the other neurotransmitter systems.

Khazan: Why do antidepressants that work for people eventually stop working? You write about how that can be one of the most frustrating things.

Slater: No one really knows why that happens. It’s one of the risks you have to keep in mind when you decide to go off your drug; it might not work if you need to go back on it again.

Khazan: Why do Prozac and other selective serotonin reuptake inhibitors—or SSRIs—so often cause sexual side effects?

Slater: When you depress the dopamine function in the brain, then you get sexual side effects. You get a blunting of the libido. Prozac does that. It raises the amount of serotonin available, but it actually depresses dopamine.

Khazan: You write how there’s no consensus around the theory that depression is caused by a chemical imbalance. Why are these drugs so widely prescribed despite that? Why do we continue to put our faith in them?

Slater: First of all, they do work two-thirds of the time. We just don’t know how they work or why they work. Drugs like Prozac can almost miraculously clear away the clutter of mental illness. The other drugs that we have, the other SSRIs or other SSNRIs, they also work. That’s why we put our faith in them.