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Most effective antidepressants potently increase synaptic levels of norepinephrine (NE) and/or serotonin (5 hydroxytryptamine [5-HT]), and in some cases dopamine (DA). Most accomplish this by inhibiting reuptake of monoamines (NE, DA, and serotonin) or inhibiting the enzyme monoamine oxidase (MAO). Although increased synaptic monoamine levels are not temporally correlated with therapeutic response, they are an essential aspect of the mechanism of action of some medications (Delgado et al. 1993). Selective partial depletion of serotonin or NE and DA causes rapid depression relapse in depressed patients on antidepressant medications that have been effective.

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Figure 23–1. Sites of antidepressant action.(1) blockade of neurotransmitter reuptake; (2) inhibition of monoamine oxidase (MAO); (3) release of neurotransmitter; (4) blockade or stimulation of receptors. 5-HT = 5-hydroxytryptamine (serotonin); 5-HIAA = 5-hydroxyindoleacetic acid.
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Table 23–1. Categories of antidepressant drugs

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