Depression Treatment: Serotonin Inhibitors (SSRI)

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Overview.

Selective-serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications for depression.  The name “selective-serotonin reuptake inhibitor” indicates how the medicine works in the brain by altering serotonin, one of the brains naturally occurring chemical messengers.  SSRIs attach to cells in the brain in a way that interferes with the cell’s ability to vacuum back up the serotonin, which ends up causing more serotonin to remain in the spaces between brain cells.  Changing this balance in serotonin levels modifies how different parts of the brain communicate with each other and can in turn improve depression symptoms. This understanding of how SSRIs work, and their improvement of depressive symptoms has facilitated a common belief in the “chemical imbalance” theory of depression, or the idea that low serotonin causes depression. However, the relationship between serotonin and depression is likely more complex than that. As an analogy, ibuprofen is helpful for a headache but headaches are not believed to be caused by low levels of ibuprofen in the brain.

What are the different types of SSRIs and what are their characteristics?  The Federal Drug Administration has approved several types of SSRIs for treating depression.  Each is listed in the table below along with important characteristics such as names, doses, and side effects.

 

Brand Name

Generic Name

Usual Dosage Range (adults)

Side Effects

Celexa

Citalopram

20-40 mg

Dizziness, headache, sleep disturbances, dry mouth, nausea

Lexapro

Escitalopram

10-20 mg

Dizziness, sleep disturbances, dry mouth, nausea, weight changes, sexual dysfunction

Fluoxetine

Prozac

20-80 mg

Restlessness, skin problems, pains

Paroxetine

Paxil, Pexeva

20-50 mg

Dizziness, headache, sleep disturbances, dry mouth, nausea, sexual dysfunction, nervousness

Sertraline

Zoloft

50-200 mg

Headache, insomnia, agitation, nausea, diarrhea, sexual dysfunction

Special Considerations.

  • In general, SSRIs are commonly prescribed because they are safer than MAOIs and Tricyclic and cause fewer side effects. There is also good data to show that SSRIs are useful for the treatment of anxiety and most also have FDA approval for treatment of anxiety.
  • The different SSRIs are all slightly different from each other in terms of the structure of their molecules, which causes them to affect serotonin levels in slightly different ways. Unfortunately, these slight differences in how they affect people are not well understood. Many people to have to experiment with several different types of SSRIs to achieve the desired antidepressant response.
  • It is important to take the medication consistently as prescribed and to be patient in finding the right dose because it can because it takes several weeks for SSRIs to “build up” in the right places. This causes a lag between when people start taking SSRIs and when the medicine starts working.  Sometimes, the side effects can start occurring before the helpful effects.
  • The evidence for SSRIs is strongest for people with moderate-severe depression.  A study published in 2012 (Fournier) created a mathematical summary of all the research on SSRIs for the treatment of depression and concluded that SSRIs are no more effective than a sugar pill for people who have minimal to moderate symptoms of depression.
  • If taken improperly or in combination with certain types of medications or supplements, some people can develop serotonin syndrome.  This happens when too much serotonin accumulates in the body and can cause symptoms ranging from mild to severe including shivering, diarrhea, fever, seizures, muscle rigidity, and death in severe, untreated forms.

Fournier, JC., DeRubeis, RJ, Hollon, SD, Dimidjian, S., Amsterdam, JD, Shelton, RC and Fawcett, J. Antidepressant drug effects and depression severity: A patient-level meta-analysis. JAMA, 303(1), 47-53.