Pharmacological principles of antidepressant efficacy

Both noradrenaline (NA) and serotonin (5-HT) appear to be involved in depression. Evidence suggests that dual-acting antidepressants, i.e. those that affect both monoamine systems, such as tricyclic antidepressants and the noradrenergic and specific serotonergic antidepressant mirtazapine, may have greater efficacy and a faster onset of action than drugs that act on a single monoamine system only, such as the selective serotonin reuptake inhibitors (SSRIs). Cell firing is reduced by SSRIs in the short-term, but is increased by mirtazapine, probably due to its actions on both NA (via alpha(2) antagonism) and 5-HT (via alpha(1)-stimulation by NA). This may help to explain clinical evidence suggesting that mirtazapine has a faster onset of action than the more selective antidepressants.