Other antidepressants include those that do not fit within the structural definition of the tricyclic antidepressants or within the activity parameters of an SSRI. Thus, these medications that at through a combination of serotonin, dopamine, and/or norepinephrine reuptake inhibition.
Buproprion
Buproprion tends to be rather stimulating in most patients, and common side effects reported or anxiety, agitation, insomnia, and sometimes restlessness. Although the mechanism of buproprion is unclear, it is often thought to be mediated by mild serotonergic and dopaminergic activity. ★A particular caution with buproprion (which it shares with tricyclic antidepressants) is an increased risk of seizures (at doses above 450 mg). There is some evidence that the seizure risk is further elevated in patients with bulimia. On the plus side, buproprion may be less likely to lead to treatment emergent affective switching in patients with bipolar disorder. Thus, it is not surprising that buproprion has come to play a bigger role in treating bipolar depression. In addition, there doesn't appear to be any evidence that buproprion affects cardiac conduction.
Mirtazapine
Mirtazapine is unique because it is an alpha-2 antagonist, and blocks 5HT3, 5HT2A, and 5HT2C receptors. It also blocks H1-histamine receptors. The efficacy of mirtazapine may be driven by the 5HT2C blockade, which stimulates release of serotonin and norepinephrine in the prefrontal cortex. The major side effects of mirtazapine are weight gain and appetite stimulation.
Duloxetine
Duloxetine is a norepinephrine reuptake inhibitor that is effective for both depression and chronic pain. Duloxetine is a potent inhibitor of 2D6, so one should be cautious of medication interactions. Although the typical dosing of duloxetine is once daily, it is a good idea, especially in medically ill patients, to begin dosing on a twice daily schedule so patients can become accustomed to its side effects.
Trazodone
Trazodone blocks 5HT2A and 5HT2C receptors as well as blocking serotonin reuptake. Trazodone was originally developed as an antidepressant, but is only effective at high doses. The somnolence associated with high doses made it impractical. Thus, it is primarily used as a sleep aid in doses ranging from 50-250 mg at bedtime. Some patients are annoyed by a 'hangover' effect they experience the morning after trazodone.
Venlafaxine
Venlafaxine is notable for blocking the reuptake of both serotonin and norepinephrine. ★It does this in a dose-dependent manner in which serotonergic reuptake predominates at lower doses and norepinephrine reuptake increases at higher doses. 2D6 converts venlafaxine to desvenlafaxine, which exhibits more norepinephrine reuptake inhibition than venlafaxine. As with escitalopram and citalopram, desvenlafaxine is now a new drug.