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How Antidepressants Work

SSRI and Tricyclic Antidepressants

Stephen Chernin/Getty Images
Prozac is one of the most
prescribed antidepressants.

Antidepressants are designed to block various aspects of the synaptic transmission process in serotonin, norepinephrine and dopamine-containing neurons in the brain. This increases the levels of these neurotransmitters. By increasing the levels of these neurotransmitters, mood and emotions should stabilize and perhaps return to normal. However, because some of these neurotransmitters (like norepinephrine) are contained in neural pathways in other parts of the brain and nervous system, some antidepressants can have side effects (like changes in blood pressure and saliva production). Also, because the pathways involved in MDD are in the lower brain and brainstem, antidepressants may interfere with other functions, like appetite, sleep and sexual function.

Antidepressants are classified according to which neurotransmitters they affect and how they affect them. Let's look at the different types of antidepressants.

Selective Serotonin Reuptake Inhibitors (SSRI)
SSRIs, the most frequently prescribed antidepressants, were introduced in the mid-1980s. SSRIs block the transport of serotonin back into the presynaptic cell. This action increases the concentration of serotonin in the synaptic cleft, increasing stimulation of the postsynaptic cells. SSRIs include the following drugs:

  • fluoxetine (ProzacTM)
  • paroxetine (PaxilTM)
  • sertraline (ZoloftTM)
  • fluvoxamine (LuvoxTM)
  • citalopram (CelexaTM)
  • escitalopram (LexaproTM)

The various SSRIs are equally effective and equally tolerated by patients. Not everyone reacts in the same way, however, so some patients may experience more side effects with one type of SSRI than with another. Most of the time, patients have to take antidepressants more than once per day. However, fluoxetine has a longer half-life -- it remains in the body longer, so patients can usually take it once a day. This lowers the chance of missing a dose. At high doses, paroxetine and sertraline will interfere with dopamine and serotonin neurotransmission.

To minimize side effects that might cause a patient to stop using the drug, primary health-care providers usually start SSRIs at low doses and slowly increase to the target dose over four to six weeks. Such side effects include nausea, dizziness, vertigo, vomiting, insomnia, anorexia, anxiety and sexual dysfunction.

Tricyclic Antidepressants and Selective Norepinephrine Reuptake Inhibitors
Tricyclic antidepressants were introduced in the late 1950s and early 1960s. Like SSRIs, these compounds block the reuptake of norepinephrine by the presynaptic cell, thereby increasing its concentration in the synaptic cleft. Tricyclic antidepressants include:

  • nortryptiline (PamelorTM)
  • maprotiline (LudiomilTM)
  • desipramine (NorpramineTM)
  • amitryptiline (ElavilTM)
  • clomipramine (AnafranilTM)
  • imipramine (TrofranilTM)

Tricyclic antidepressants affect heart rate and blood pressure because norepinephrine is also used in the autonomic nerves that control these functions. Their side effects include postural hypotension (drop in blood pressure upon standing), tachycardia (rapid heart rate), dry mouth, urinary retention and blurry vision. Tricyclic antidepressants are not used often because they are toxic and easily overdosed. However, for patients who do not tolerate SSRIs or other antidepressants, tricyclics are effective. Physicians must monitor the patient closely for toxic side effects.

Tric­yclic antidepressants are nonselective inhibitors of norepinephrine reuptake because their chemical structures look like norepinephrine. Reboxetine (EdronaxTM­) is a more specific reuptake inhibitor because it binds better to the reuptake transporter, but it isn't available in the United States.