SSRI (Selective Serotonin Reuptake Inhibitors): Important Facts to Know

SSRI (Selective Serotonin Reuptake Inhibitors): Important Facts to Know

(1) Do SSRIs have Active Metabolites?

  • Fluoxetine (Norfluoxetine with half life of 7–14 days).

Note: R-norfluoxetine is not active in terms of serotonin inhibition, while S-norfluoxetine is a more potent serotonin reuptake inhibitor than the parent drug. (Source: Neuropharmacology. 1992;31(10):997–1000)

  • Sertraline (N-desmethylsertraline with half life of 2–3 days)

Note: N-desmethylsertraline has limited activity and is less potent than sertraline as a serotonin uptake inhibitor.

  • Escitalopram (S-demethylcitalopram):

Note: this is present at approximately 1/3rd the level of escitalopram. however this metabolite is a weak inhibitor of serotonin reuptake and does not contribute appreciably to the therapeutic activity of escitalopram.

  • Citalopram (Demethylcitalopram):

Note: Studies show that citalopram is at least 8 times more potent than its metabolites in the inhibition of serotonin reuptake, suggesting that the metabolites evaluated do not likely contribute significantly to the antidepressant actions of citalopram.

  • Fluvoxamine and Paroxetine: no metabolites.

 

(1.a) What is the clinical implication of SSRIs with long-acting metabolites?

  • Less problem if patient misses their dose and less risk of discontinuation syndrome.
  • Problematic if toxicity develops or drug-drug interactions develops- symptoms will persist for long duration after drug discontinuation.

 

Source: D.A. Ciraulo and R.I. Shader (eds.), Pharmacotherapy of Depression

(2) Do SSRIs have Long Acting Formulations?

  • Fluoxetine:
    1. PROZAC Weekly™ capsules, a delayed-release formulation, contain enteric-coated pellets of fluoxetine hydrochloride equivalent to 90 mg of fluoxetine.

 

  1. Clinical Fact: Separate the first 90 mg weekly dose and the last 20 mg once-daily dose by 1 week.

 

  • Paroxetine CR:
  1. Dosage: 25 mg to 62.5 mg once a day.
  2. Clinical Fact: Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole. 

 

  • Fluvoxamine CR:
  1. Recommended starting dose is 100 mg at bedtime, with weekly increases of 50 mg as tolerated to maximum effect, not to exceed 300 mg/day.

(3) Which Cytochrome P450 is inhibited by SSRIs (Important for Drug Interactions)?

  • Fluoxetine: Strong inhibition for 2D6 and Moderate inhibition for 2C19.
  • Sertraline: Moderate inhibition for 2C19.
  • Paroxetine: Strong inhibition for 2D6.
  • Fluvoxamine: Strong inhibition for 2C19 and 1A2.
  • Citalopram: None
  • Escitalopram: None


Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


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