Single-Action Versus Dual-Action Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) have become the most popular antidepressants over the last decade, largely because they have a better side effect profile than the medications that were widely used previously, the tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs). The SSRIs mostly have one main mechanism of action, inhibition of serotonin reuptake. A few of the TCAs are single action but many are dual action, acting mainly on the neurochemicals serotonin and norepinephrine, among others. The MAOIs are multiple-action medications, acting on monoamines, which include serotonin and norepinephrine. While the selectivity of the SSRIs results in an improved side effect profile over the earlier dual-action antidepressants, it may also reduce their antidepressant effect. SSRIs may have a slower onset of action, result in lower remission rates, and be less effective for the physical symptoms associated with depression than TCAs and MAOIs. Newer dual-action medications have been developed that inhibit the reuptake of both serotonin and norepinephrine. These medications, called serotonin-norepinephrine reuptake inhibitors, may have fewer side effects than the earlier dual-action medications and potentially reduce the symptoms of depression more effectively than the SSRIs.