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How Different Antidepressants Work

Other Antidepressants: Tetracyclics and SARIs

  • Tetracyclics are another class of antidepressant with drugs such as Asendin, Ludiomil, Mazanor, and Remeron. Although it affects neurotransmitters, Remeron doesn't prevent reuptake in the same way. Instead, it seems to stop neurotransmitters from binding with specific receptors on the nerves. Because the norepinephrine and serotonin don't bind to the receptors, they seem to build up in the areas between the nerve cells. As a result, the neurotransmitter levels rise.
  • Serotonin antagonist and reuptake inhibitor (SARIs) appear to act in two ways. They prevent the reuptake of serotonin. But they also prevent serotonin from binding with the cell receptors. Examples include nefazodone and trazodone.

 

Older Antidepressants: Tricyclics and MAOIs

These drugs were among the first to be used for depression. Although they're effective, they can have serious side effects and can be especially dangerous in overdose. Nowadays, many doctors only turn to these drugs when newer -- and better tolerated -- medicines haven't helped. Tricyclics and MAOIs might not be the best approach for someone who was just diagnosed. But they can sometimes be very helpful for people with treatment-resistant depression, or certain forms of depression (such as depression with anxiety).

  • Tricyclic antidepressants (TCAs) include amitriptyline (Elavil), desipramine (Norpramin), nortriptyline (Pamelor), and imipramine (Tofranil). Like reuptake inhibitors, tricyclics seem to block the absorption of serotonin and epinephrine into the nerve cells. Because of the potential side effects, your doctor might recommend regular blood tests to monitor the level of tricyclics in your system. These medicines might not be safe for people with certain heart rhythm problems.
  • Monoamine oxidase inhibitors (MAOIs) include Emsam, Marplan, Nardil, and Parnate. These drugs seem to work a little differently. Monoamine oxidase is a natural enzyme that breaks down serotonin, epinephrine, and dopamine. MAOIs block the effects of this enzyme. As a result, the levels of those neurotransmitters might get a boost.
    The downside is that MAOIs also prevent the body's ability to break down other medicines metabolized by this enzyme (such as Sudafed, or stimulants) -- raising the risk for high blood pressure -- as well as an amino acid called tyrosine, which is found in certain foods like aged meats and cheeses.  MAOIs also shouldn't be combined with other medicines that can raise serotonin (such as certain migraine medicines, or other antidepressants), because that can cause a buildup of excessive serotonin (called "serotonin syndrome"), which could be life-threatening.

 

Treatment-Resistant Depression: Getting the Most from Your Antidepressants

It's worth remembering that a lot of what we think about antidepressants is still speculative. We don't really know if low levels of serotonin or other neurotransmitters "cause" depression, or if raising those levels will resolve it. We don't know enough about brain chemistry to say what's "balanced" or "unbalanced." It's possible that antidepressants have other unknown effects, and that their benefits don't have as much to do with neurotransmitter levels as they might with other effects, such as regulating genes that control nerve cell growth and function.

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