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Tricyclic antidepressants

Tablets spilling out of a bottle.

Tablets spilling out of a bottle.

Credits:Wellcome Library, London

Tricyclics, named for their three-ring chemical structure, were among the first modern psychiatric drugs. Together with monoamine oxidase inhibitors (MAOIs), tricyclics dominated the antidepressants market for over three decades, until selective serotonin reuptake inhibitors (SSRIs) were developed in the 1980s. The first tricyclic antidepressant was imipramine, a drug chemically related to the first drug used against schizophrenia. In the mid 1950s, shortly after the first antidepressants and anti-schizophrenia drugs were discovered, a researcher affiliated with Swiss pharmaceutical company Geigy found imipramine raised the mood of depressed patients. Unlike earlier antidepressants, it produced no ‘energising’ effects in non-depressed people. Geigy argued the earlier drugs boosted energy levels temporarily, masking the symptoms of depression. Tricyclic antidepressants, they argued, instead targeted the biochemical roots of the illness.

The way tricyclics worked remained unknown for decades. Research eventually suggested they affected serotonin and other neurotransmitters, much like later SSRIs. They were less toxic than other antidepressants of the time, but they carried unpleasant side effects including dry mouth, constipation, drowsiness and changes in weight. Tricyclics were also deadly for patients who overdosed, so suicidally depressed patients could only use them under close supervision in mental hospitals.


D Healy, The Anti-Depressant Era (Harvard University Press, 1997)



A mental disorder that has symptoms of delusions, hallucinations and a loss of a sense of self and relationship to the external world that lasts over a long period of time (more than six months).


A mental state associated with acute sadness. Activity can be decreased, especially interaction with others, and sleep, appetite, and concentration can also be disturbed.