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Despite evidence for and against, there remains one major problem with the monoamine theory of depression. All antidepressants take weeks to have an effect, which is far longer than it takes to alter brain amines. It has been suggested that effects of antidepressants are due to adaptive changes in the brain, which may involve down regulation of receptors or some other change in their sensitivity. Some of the newer types of antidepressants do not facilitate monoamine transmission at all.

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