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?
- PROZAC Weekly™ capsules, a delayed-release formulation, contain enteric-coated pellets of fluoxetine hydrochloride equivalent to 90 mg of fluoxetine.
- Clinical Fact: Separate the first 90 mg weekly dose and the last 20 mg once-daily dose by 1 week.
- Paroxetine CR:
- Dosage: 25 mg to 62.5 mg once a day.
- Clinical Fact: Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole.
- Fluvoxamine CR:
- 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
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Dr. Harvinder Singh, M.D. (Admin)
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