There is an old joke that applies to the past–and only the past–of psychopharmacology: One dark night, a police officer notices a man furiously searching for something beneath a street lamp. “What are you looking for?“ he asks. The man replies, “My car keys. If I don't find them, I'll never get home.” “Well,” asks the police officer, “did you lose them here?” “No,” the man replies. “But this is the only place on the block that has any light.”

For example, once it was discovered that tricyclic antide pressants antagonize the presynaptic neuronal reuptake of norepinephrine (NE), the idea was put forth that the problem in depression is some abnormality in noradrenergic function. Some of the tricyclics, like desipramine and nortriptyline, are actually selective NE reuptake inhibitors. However, once it became apparent that selective serotonin (5-HT) reuptake inhibitors (SSRIs) are also effective in treating depression, consideration of the noradrenergic system suddenly disappeared from the literature, replaced by a new hypothesis that depression is caused by deficient serotonergic neurotransmission.