How antidepressants were developed.

The 1950s saw the advent of the first antidepressants, revolutionary because there were few treatments available at the time.  Interestingly, it was the accidental discoveries in unrelated fields of medicine that brought this about.  Infectious disease researchers developing a new drug for tuberculosis, isoniazid, (still used today) realized that a slightly altered version of the drug, known as iproniazid, produced unexpected positive behavioral effects in patients.  Hospital patients tested on this drug reported their spirits lifted, were ‘dancing in the hall’ and showed a reversal of depressive symptoms.  In the same time period, surgeons developing new sedating agents discovered 2 important psychiatric medications:  One was chlorpromazine, a drug that was the first antipsychotic, and with a chemical modification to it, the drug imipramine, which would become an important antidepressant.   What iproniazid and imipramine had in common was that they both enhanced levels of monoamines, a class of chemicals that comprise some neurotransmitters, messengers used by brain cells to communicate with each other.  That realization gave birth to the “monoamine hypothesis”,,  the theory that increasing levels of monoamine neurotransmitters leads to relief of depression.
Fast forward 60 years and most antidepressants have been engineered based on the monoamine hypothesis.    Older antidepressants, like the tricyclic antidepressants and the monoamine oxidase inhibitors, increase a multiple number of these neurotransmitters, like dopamine, norepinephrine, and serotonin.  The newer generation of antidepressants arriving in the 1980’s, harkened a new era,  when the  benign side effects of these new drugs shifted the treatment of mood disorders. from the severely afflicted to millions more patients worldwide with milder symptoms.