Aug. 2, 2022 – They have done us a favour by corralling the evidence that says as much, even if we knew this to be the case.

But the death of the chemical imbalance theory has no bearing on whether antidepressants that affect the serotonin system are effective. These medications weren’t developed on this premise. In fact quite the opposite is true – the chemical imbalance theory was based on an emerging understanding of how antidepressants were shown to work.

How did the ‘chemical imbalance’ theory start?

The first two antidepressant medications, both discovered in the 1950s, were observed to have positive effects on mood as side-effects of their hoped-for functions. Iproniazid was developed as a treatment for tubercolosis, and imipramine as an antihistamine. We know now that ipronizaid is a monoamine oxidase inhibitor – it stops the enzyme that breaks down serotonin and similar brain chemicals. But we didn’t know this when its antidepressant effects were first observed in 1952.

Imipramine is a tricyclic antidepressant and, among other effects, it blocks the reuptake of serotonin after it has been secreted, also allowing more to stay in the brain.

A simple hypothesis then presented itself: if both classes of antidepressants were shown to increase brain levels of serotonin, then depression must be caused by low levels of serotonin.


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