the only people for whom these drugs are prescribed are those who can
manage their diets.
The action of MAO inhibitors led researchers to believe that depres-
sion was caused by a norepinephrine deficit, which they assumed disrupted
activity in the reward centers of the brain. In the 1960s, as new neurotrans-
mitters were being discovered, each one was in its day seen as implicated
in depression. Norepinephrine, acetylcholine, dopamine, and serotonin
have all had their advocates.
THE AGE OF SEROTONIN. Tricyclic antidepressants were originally
developed to increase available norepinephrine, but they also increased
serotonin, which in the 1980s became the odds-on favorite as the neuro-
transmitter whose depletion caused depression. Then came Prozac and
the selective serotonin reuptake inhibitors, and depression came to be
understood, or at least advertised, as a serotonin deficiency that can easily
be treated in any doctor’s office.
There are several problems with this theory:
First, not all depressions respond to serotonin-enhancing drugs. This
one is so easy to fix, it needs little explanation. Newer products like Serzone,
Effexor, and Remeron have been developed that increase available nore-
pinephrine as well as serotonin. Each new antidepressant is formulated to
bind with either very specific serotonin and/or norepinephrine receptors,
or as many different kinds of receptors as possible.
The second problem, more difficult to explain, is that most of the
drugs that increase available serotonin or norepinephrine do so within a
day or two, but take at least two weeks to have an effect on depression. It
seems apparent that increasing serotonin has other, slower repercussions,
or that something else besides increasing serotonin is actually responsible
for the antidepressant effect.
THE SUPERSENSITIVITY HYPOTHESIS. There are, of course, theories
to explain the delay. One suggests that serotonin receptors are “super-
sensitive” in depressed people, that they overreact to small amounts of
serotonin, essentially telling the cell that there is already too much sero-
tonin when there is really not enough. Strange as this sounds, there are
several disorders—notably Type II diabetes—that operate similarly.
According to supersensitivity theory, serotonergic drugs affect the
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