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Clinician’s Corner: Selective Serotonin Reuptake Inhibitors (SSRI)

Selective Serotonin Reuptake Inhibitors (SSRI) have been around for 32 years with the introduction of Prozac (fluoxetine) in 1987.  This was a big boost in the treatment of depression for our patients.

Mechanism:  Allows more serotonin to be available in the synapses which improves moods.

Ground Rules for Prescribing Antidepressants

  • There is a 2 to 4-week lag time to see benefits, but side effects occur rapidly
  • An adequate dose and duration of treatment of at least 4-8 weeks are required to establish an adequate trial of antidepressant.
  • Antidepressant dose should be increased if patient compliance is good and no response after 3 weeks. If partial response, adjust dose in 2 weeks.
  • 25% of patients who don’t respond to one SSRI will respond to another. Therefore, it’s reasonable to switch from one SSRI to another if a patient is not responding. However, if a patient fails more than one SSRI, then a class switch should be considered.


  • highest risk of drug interactions: fluoxetine (Prozac®), fluvoxamine (Luvox®), and paroxetine (Paxil®).
  • lowest risk of drug interactions: include citalopram (Celexa®), escitalopram (Lexapro®), mirtazapine Remeron®, venlafaxine (Effexor®), and desvenlafaxine (Pristiq®).

SSRI (Selective Serotonin Reuptake Inhibitors)


  • Common side effects for SSRI: headache, nausea, nervousness, insomnia, agitation, sexual dysfunction, teeth grinding
  • Costs of SSRI: All SSRI are available generically.  Are now very inexpensive.
  • Bleeding Risk: Absolute risk is small.  Greater risk when combined with Aspirin or NSAIDs
  • Risk of Torsades: Sertraline, paroxetine, and fluoxetine seem less likely to cause irregular heartbeat.
  • HYPONATREMIA: older patients are more likely to develop low sodium with an SSRI or SNRI or mirtazapine than younger counterparts. Be sure to monitor sodium especially in patients with heart failure, or those taking hydrochlorothiazide.
  • FALL RISK: SSRI are on Beers list for patients with a history of falls or fractures. Watch for sedation and blurred vision to decrease fall risk

Selective Serotonin Reuptake Inhibitors (SSRI) 

Citalopram (Celexa®)

    • Do not exceed 40 mg/day for anyone. Max= 20 mg/day for most patients over age 60.
    • Higher doses of citalopram increase the risk of QT prolongation and torsades.
    • Caution: using citalopram in patients at risk due to underlying cardiac disease or low serum potassium or magnesium.

Escitalopram (Lexapro®)

  • S-isomer (active isomer) of Celexa
  • When citalopram is not utilized based on risk factors for TdP, use of escitalopram is not likely the safest alternative. Based on current literature, fluoxetine, fluvoxamine, and sertraline appear to have similar, low risk for QT prolongation, and paroxetine appears to have the lowest risk. https://www.ncbi.nlm.nih.gov/pubmed/24259697

Fluoxetine (Prozac®)

  • LONGEST half-life of SSRI’s (1 to 3 days)
    • Active metabolite (norfluoxetine) has 4-16-day half-life.
  • Along with sertraline (Zoloft®) is the MOST activating of SSRI

Paroxetine (Paxil®)

  • Paroxetine (Brisdelle® 7.5mg) marketed for hot flash treatment
  • MOST sedating of SSRI
  • MOST anticholinergic side effect of SSRI
  • Pregnancy Category D
  • Considered by most to be the “dirtiest” SSRI

Sertraline (Zoloft®)

  • MOST Activating SSRI (along with Prozac)


SSRI Starting Dose Target Dose
Citalopram 20 20 to 40
Escitalopram 10 10 to 20
Fluoxetine 20 20 to 60
Paroxetine 20 20 to 40
Sertraline 50 50 to200

These drugs work well for patients, but only if taken every day as prescribed.  Your Thompson Pharmacist can help get your medications synchronized with our “Med Synch” plan.  We can also provide you with pill packs, that make taking complicated medication regimens easy to handle.  We’re the drug experts when it comes to your medications.  You need to take them!!

Go Ahead and ASK… at Thompson Pharmacy it’s ALL FOR YOU!