An article about cyclic antidepressants: how they work, how to take them, and what side effects to expect.

"What I remember most about being depressed was always being exhausted. I could never get to sleep at night, and when I did, I had nightmares. Then I'd wake up in the morning and have to drag myself to work. And in all that time -- four or five years, I guess -- I never once enjoyed anything. I was actually planning my own suicide when my doctor referred me to a psychiatrist who put me on imipramine. For the first time in years, I finally began to get some pleasure out of life."

-- Sam, 43

Before Prozac, tricyclics were the first line of defense against encroaching depression, and had been ever since imipramine's release in 1958 under the brand name Tofranil. Today, tricyclics are a less popular choice than the new generation of antidepressants, but they're still an important weapon in the antidepressant arsenal for a subset of people who don't respond to anything else. This type of medication is used to help relieve the symptoms of major depression.

Common Cyclic Antidepressants
(Lower doses are used with elderly patients)

Before tricyclics were developed, psychiatrists treating severely depressed clients had only two real choices: amphetamines or electroshock therapy. Imipramine was discovered by Swiss scientists searching for a successful schizophrenia treatment; it turned out that imipramine didn't do much for schizophrenia at all. What it did do very well was perk up depressed patients.

With the discovery of imipramine, doctors finally had a drug that relieved a person's underlying depression. And when scientists realized how effective imipramine was -- about 70 percent of depressed patients responded to this drug -- they flocked to the laboratories in search of similar drugs based on imipramine's three-ring ("tricyclic") antihistaminic chemical structure. Before long, laboratories all over the country began churning out tricyclic clones, each one a little different from, but none any better than, imipramine itself. A later-developed drug in this class, maprotiline (Ludiomil), had four rings and was therefore called "tetracyclic." Taken together, the tricyclics and tetracyclics are known as "heterocyclics" or "cyclics."

But while all these cyclics were effective, not one provided the perfect solution to depression for which scientists had been searching.