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The “chemical imbalance” theory of depression, for example, also known as the catecholamine, monoamine, or serotonin deficiency hypothesis, was based on the chemical action of the first generation of antidepressants, which were discovered serendipitously and found to act on monoamine pathways to increase monoamine concentrations (López‐Muñoz & Alamo, 2009). We now know that the “chemical imbalance” hypothesis of depression is false. First, the fact that drugs that increase monoamine concentrations also reduce depressive symptoms (O'Donnell, 2011) is not strong evidence that depression is caused by a deficiency of monoamines. Aspirin reduces headache symptoms but headaches are not caused by an aspirin deficiency. Second, antidepressant drugs increase monoamine concentrations almost immediately (within minutes), but their antidepressant effects only appear after a few weeks (Frazer & Benmansour, 2002; Harmer, Goodwin, & Cowen, 2009). Third, other drugs, such as cocaine, increase monoamines (Kalsner & Nickerson, 1969; Kuhar, Ritz, & Boja, 1991) but are not effective antidepressants. Fourth, some antidepressant drugs, such as tianeptine, decrease monoamines (Baune & Renger, 2014; McEwen et al., 2010). Fifth, depletion of monoamines does not induce depression in non‐depressed individuals (Ruhé, Mason, & Schene, 2007). In summary, although monoamines might play some role in depression, there is no evidence that depression is caused by a simple imbalance of serotonin, norepinephrine, or any other neurotransmitter or biochemical (Kendler, 2008; Lacasse & Leo, 2015, and references therein).
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Kristen L. Syme (Mental health is biological health: Why tackling “diseases of the mind” is an imperative for biological anthropology in the 21st century)