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Depression and SSRIs

Written by sshowalter, ritasharma, Gary Wu.

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Selective serotonin reuptake inhibitors (SSRIs) are the newest class of pharmacological antidepressants. They are currently the most popular class of antidepressant medications because of their relative safety in comparison to monoamine oxidase inhibitors (MAOIs) and tricyclics (TCAs).

Effect of SSRIs on Depression

SSRIs work by selectively blocking serotonin reuptake receptors, increasing the levels of serotonin in the synaptic clefts (spaces between neurons) of the brain. In contrast, tricyclics (TCAs) and monoamine oxidase inhibitors (MAOIs) work on multiple neurotransmitters, in addition to serotonin. This difference contributes to SSRIs increased safety in overdose and fewer side effects in comparison to other antidepressant medications.

Read more details about SSRIs.

Research Evidence on SSRIs

Studies show that selective serotonin reuptake inhibitors (SSRIs) are as effective as tricyclics (TCAs), but with greater safety in use, greater ease in dosage, and less side effects. SSRIs have been shown to be effective for mild to moderate forms of depression. Other treatments should be considered for more severe types of depression.

Some studies have shown that it is more difficult for people with low folate levels to experiences the beneficial side effects of SSRIs and therefor supplementation may be warranted.7

Read more on Depression and Folate

How to Use SSRIs

A physician will typically diagnose one of these brand names for patients diagnosed with depression.

Drug name (Brand name) Daily Dose
Fluoxetine (Prozac) 20-60 mg
Fluvoxamine (Luvox) 10-300 mg
Paroxetine (Paxil) 20-50 mg
Sertraline (Zoloft) 50-200 mg

Possible side effects of SSRIs include:

  • Drowsiness
  • Dryness of mouth
  • Blurred vision
  • Nausea
  • Dizziness
  • Difficulty sleeping
  • Sexual dysfunction
  • Risk of severe mood and behavior changes
  • Suicidal thoughts and actions

Gastrointestinal upset is the most common side effect that users experience. These include nausea, diarrhea, and cramping. It is commonly recommended that users take SSRIs with food and an antacid or antiemetic for the first 2-3 weeks of treatment.

SSRIs also activate the central nervous system, which can result in agitation, anxiety, restlessness, and insomnia.

FDA issued a warning that combining an SSRI with one of the commonly-used "triptan" medications for migraine headaches can cause serious side effects such as agitation, hallucinations, elevated body temperature, and rapid changes in blood pressure. (6)

Other side effects can include headache, dry mouth, excessive sweating, tremor, and sexual dysfunction.

Do not take selective serotonin inhibitors (SSRIs) with monoamine inhibitors (MAOIs).

The first SSRI on the market was fluoxetine (Prozac). The newer agents are: citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft).8 They all share the same side effects but in varying degrees. Unlike TCAs, they interact very little with other receptors besides the serotonin 5-HT reuptake receptor. Their side effects tend to be related to increased serotonin activity: nausea, gastrointestinal upset, sweating, anxiety, insomnia, headache, restlessness, and sexual dysfunction. This class of drugs is prescribed for mild to moderate depression.8

Other Uses

Selective serotonin reuptake inhibitors (SSRIs) have also been shown to be effective in treating obsessive compulsive disorder (OCD), panic disorder, and eating disorders for some people.


1 Charney, D.S & Delgado, P.L. (1992). Current concepts of serotonin neuronal function and the pathophysiology of depression. Experimental Approaches to Anxiety and Depression. San Antonio: Wiley.

2 DeBaffista, C. (1997). Medical Management of Depression. Durant: EMIS, Inc.

3 Moncrieff, J., Wessely S., & Hardy R. (2008). Active placebos versus antidepressants for depression. Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD003012. DOI: 10.1002/14651858.CD003012.pub2

4 Biggs, J.T., Spiker D.C., Petit J.M. et al. (1977). Tricyclic Antidepressant overdose: Incidence and Symptoms. Journal of the American Medical Association, 238.

5 Micó J., Ardid D., Berrocoso E., & Eschalier A. (2006). Antidepressants and pain. Trends in Pharmacological Sciences, 27(7).

6 Depression Handbook, National Institute of Mental Health, 2008

7 Alpert, M., Silvia, R.R. & Pouger, E.R. (2003). Prediction of Treatment REsponse in Geriatric Depression from Baseline Folate Level: Interaction with an SSRO or a Tricyclic Antidepressant. Journal of Clinical Psychopharmacol23, 309-313.

8 Preston, J. D., O'Neal, J. H., & Talaga, M. C. (2005). Handbook of clinical psychopharmacology for therapists. Oakland, CA: New Harbinger Publications, Inc.

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