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How Antidepressants Work

SNRI, MAOI and NaSSA Antidepressants

Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
These drugs were introduced in the mid-1990s and block the reuptake of both serotonin and norepinephrine by binding to the transporters of these neurotransmitters on the presynaptic cell. SNRIs include:

  • bupropion (WellbutrinTM) -- blocks dopamine and norepinephrine reuptake as well
  • duloxetine (CymbaltaTM)
  • venlafaxine (EffexorTM)

The side effects of these drugs are similar to, but less than, those of SSRIs. Bupropion and duloxetine, in particular, have minimal side effects in the areas of sexual dysfunction and weight gain.

MAO Inhibitors

Monoamine Oxidase Inhibitors (MAOI)
An enzyme called monoamine oxidase can degrade serotonin and norepinephrine in the synaptic cleft and presynaptic cell. MAOIs block this degradation, increasing the concentration of the neurotransmitters. MAOIs include:

  • phenelzine (NardilTM)
  • tranylcypromine (ParnateTM)
  • selegiline (EldeprylTM)
  • isocarboxazid (MarplanTM)
  • moclebemice (ManerixTM)

Because these drugs can interfere with norepinephrine, they can have cardiovascular side effects. Most commonly, patients must limit their consumption of foods containing tyramine because the drugs interact with tyramine to cause hypertension (high blood pressure). Tyramine can be found in foods like soy sauce, sauerkraut, chicken and beef livers, aged cheese, sausage, cured meat and fish, yogurt, raisins, figs and sour cream. Patients also have to refrain from consuming alcohol when on these antidepressants. Because of these interactions, doctors do not prescribe this class of antidepressants as frequently as others.

Noradrenergic and Specific Serotonin Antidepressants (NaSSA)
Some of these compounds were introduced in the mid-1980s and others even more recently. NaSSAs block negative feedback effects on norepinephrine and serotonin secretion by the presynaptic cell. This action increases the concentrations of these neurotransmitters in the synaptic cleft. They also block some serotonin receptors on the postsynaptic cell, which enhances serotonin neurotransmission. These compounds include

  • Mirtazipine (RemeronTM)
  • Trazodone (DesyrelTM)
  • Nefazodone (SerzoneTM)
  • Mianserin (BolvidionTM)

The most common side effects are drowsiness, dry mouth, increased appetite and weight gain.

Remember that the available antidepressants are about equally effective in treating MDD. So, choices are based on patient's age, family history, drug tolerance, side effects and past response to antidepressants.

On the next page, we'll look at the role of antidepressants in MDD treatment.