Antidepressant Medications

1957

Roland Kuhn (1912–2005)

In 1952, a drug under development for use with tuberculosis patients, iproniazid, was found to be effective in treating depression. Approved for use in 1958, it was withdrawn three years later when it was found to cause serious liver damage. In 1955, imipramine was being considered as a treatment for people suffering from schizophrenia at a mental hospital in Switzerland, but the results were not positive. Psychiatrist Roland Kuhn decided to try the drug on forty depressed patients, and the results were all positive. Patients became livelier, their voices were stronger, they were able to effectively communicate, and hypochondriacal complaints all but disappeared. He published his results in 1957.

Imipramine moved to the market under the brand name Tofranil. It was the first of what soon became a family of drugs labeled tricyclics (so named because of their three-ring chemical structure). Tricyclics work by inhibiting the reuptake of the neurotransmitters norepinephrine and, to a lesser degree, serotonin, thus initially making more of them available for use in the brain. There can be unpleasant side effects, however, such as dry mouth, constipation, weight gain, and sexual dysfunction.

Another antidepressant that also works by inhibition was discovered shortly after imipramine. The class of drugs known as monoamine oxidase inhibitors (MAOI) prevents the action of an enzyme, monoamine oxidase, which breaks down such neurotransmitters as serotonin and norepinephrine. MAOI side effects are even more dangerous than those of the tricyclics, so they are seldom prescribed today.

In 1987, a second-generation antidepressant with the trade name Prozac was approved for use by the US Food and Drug Administration. Prozac and other drugs like it are selective serotonin reuptake inhibitors (SSRIs). Just as their name implies, they inhibit the reuptake of serotonin in the synapse. The response has been phenomenal: within three years of its release, Prozac was the number-one drug prescribed by psychiatrists, and by 1994 it was the number-two best-selling drug of any kind in the world. It does not have many of the side effects of other antidepressants. Indeed, it is used by millions of people who suffer from no mental disorder at all but who use the drug to enhance their personality, lose weight, or increase their attention spans.

SEE ALSO Antianxiety Medications (1950), Antipsychotic Medications (1952)

Many species of passionflower have been found to contain beta-carboline harmala alkaloids, which are MAO inhibitors with antidepressant properties.