Fluoxetine
From Pharmacopedia
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SSRI, Anxiolytic, Antidepressant
Fluoxetine
Prozac
Fluoxetine was the first of a long line of SSRIs. It is notable for its extremely long half-life and relative lack of withdrawal syndrome. It can also be useful in helping taper and discontinue other SxRI medicines.
None required
Sertraline, Duloxetine
Experience
No personal reports yet
1 provider report · avg efficacy 40.0/100 · avg side-effect burden 40.0/100 · 150 patients managed total
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Problems
<indication ref="depression" author="MDElliottMD"/> <indication ref="anxiety-disorders" author="MDElliottMD"> Including generalized anxiety, panic, and social anxiety. </indication> <indication ref="panic" author="MDElliottMD"/> <indication ref="social-anxiety" author="MDElliottMD"/> <indication ref="ocd" author="MDElliottMD"/> <indication ref="ptsd" author="MDElliottMD"> Potentially. </indication>
+ Add a problemTitration strategies
Standard adult or child+1
Start no higher than 10 mg for the first dose. May increase by 10 mg every 2–12 weeks, or remain at 10 mg if the response is adequate, up to a typical starting maximum of 40 mg. Absolute max: 80 mg.
OCD+1
Start at 10 mg daily; increase by 10–20 mg every 2–6 weeks, up to 80 mg. OCD typically requires elevated doses (60–80 mg).
Effects
- Anxiolysis no reports yet ~33% +67.0 (n=1)Classically starting at 3–4 weeks and improving for another 8–12.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Delayed orgasm/ejaculation 0% — (n=3) ~80% +33.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Mood enhancement no reports yet ~5% +67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Nausea no reports yet ~5% -33.0 (n=1)Common, often improves over 1–2 weeks.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Decreased libido no reports yet ~33% -100.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Temporary erectile dysfunction no reports yet ~20% -67.0 (n=1)Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
- Persistent Sexual Dysfunction no reports yet ~0% -100.0 (n=1)Historically associated with SSRIs.Did you experience this?How often have you seen this?How was it? (-100 worst, +100 best)How was it? (-100 worst, +100 best)
Anorgasmia no reports yet ~5% -100.0 (n=1)
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Pharmacokinetics
Absorption
70–90%[3] oral bioavailability.Distribution
Fluoxetine has plasma protein binding of approximately 94.5%, bound to albumin and alpha-1 glycoprotein. Fluoxetine readily crosses the blood–brain barrier, with a brain-to-plasma ratio of 2.6:1 in humans. The volume of distribution (Vd) of fluoxetine and its metabolite ranges between 20 to 42 L/kg. Some studies report that fluoxetine has the maximum volume of distribution (Vd) of any SSRI (between 14 and 100 L/kg).[3]Metabolism
Fluoxetine's active metabolite is norfluoxetine, produced when the cytochrome P450 enzyme (CYP2D6) acts on it. Prescribers must remember that fluoxetine has several drug-drug interactions due to its metabolism through the CYP2D6 isoenzyme. Additionally, norfluoxetine can have an inhibitory effect on CYP3A4. Fluoxetine has a half-life of 2 to 4 days, and its active metabolite norfluoxetine has a half-life of 7 to 9 days. Approximately 7% of individuals definitively exhibit poor metabolism of fluoxetine due to reduced activity of CYP2D6.Interactions
Pharmacogenomic + mechanism interactions
Pharmacokinetic mechanismSubstrate / metabolism relationships from primary literature
FDA Drug Interactions Table: strong index inhibitor of CYP2D6.
⏱ mechanism-based, interaction persists ~4-6 weeks after stopping the inhibitorRate this interaction. Reports are anonymous and help curate the page.
Clinical relevance: does this interaction matter in practice?trivialcritical
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Inferred from pharmacokinetic dataMaterialised by the inference engine; provenance shown per row
Fluoxetine inhibits CYP2D6 (inhibitor_strong, intensity 90); Codeine is a prodrug_activated_by of CYP2D6 (intensity 100). Derived: Codeine exposure lowered.
⏱ mechanism-based, interaction persists ~4-6 weeks after stopping the inhibitorInferred via Enzyme:CYP2D6 (exposure lowered)
Rate this interaction. Reports are anonymous and help curate the page.
Clinical relevance: does this interaction matter in practice?trivialcritical
Confidence in this inference: is the inferred magnitude sound?overstatedsound
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Fluoxetine inhibits CYP2D6 (inhibitor_strong, intensity 90); Nebivolol is a substrate_major of CYP2D6 (intensity 80). Derived: Nebivolol exposure raised.
⏱ mechanism-based, interaction persists ~4-6 weeks after stopping the inhibitorInferred via Enzyme:CYP2D6 (exposure raised)
Rate this interaction. Reports are anonymous and help curate the page.
Clinical relevance: does this interaction matter in practice?trivialcritical
Confidence in this inference: is the inferred magnitude sound?overstatedsound
Mechanism description, if it needs work:
Kinetics annotation:
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Fluoxetine inhibits CYP2D6 (inhibitor_strong, intensity 90); Desipramine is a substrate_major of CYP2D6 (intensity 80). Derived: Desipramine exposure raised.
⏱ mechanism-based, interaction persists ~4-6 weeks after stopping the inhibitorInferred via Enzyme:CYP2D6 (exposure raised)
Rate this interaction. Reports are anonymous and help curate the page.
Clinical relevance: does this interaction matter in practice?trivialcritical
Confidence in this inference: is the inferred magnitude sound?overstatedsound
Mechanism description, if it needs work:
Kinetics annotation:
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Your own experience with this combination:
Experience (1 a little, 5 a lot)
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Fluoxetine inhibits CYP2D6 (inhibitor_strong, intensity 90); Dextromethorphan is a substrate_major of CYP2D6 (intensity 80). Derived: Dextromethorphan exposure raised.
⏱ mechanism-based, interaction persists ~4-6 weeks after stopping the inhibitorInferred via Enzyme:CYP2D6 (exposure raised)
Rate this interaction. Reports are anonymous and help curate the page.
Clinical relevance: does this interaction matter in practice?trivialcritical
Confidence in this inference: is the inferred magnitude sound?overstatedsound
Mechanism description, if it needs work:
Kinetics annotation:
Is this row worth surfacing?
Your own experience with this combination:
Experience (1 a little, 5 a lot)
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Patient experience
MDMA exp n/a/5 outcome n/a (n=1) exp 3.0/5 outcome -33.0 (n=1)
How much experience do you have with this combination (1 a little, 5 a lot)?
How did it go? (-100 worst, +100 best)
- Generally a blunted MDMA effect is reported, though I have heard many reports of people having full effects despite full-dose steady state SSRI use comcotitantly
Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
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- checking this mechanism here
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) no reports yet exp 4.0/5 outcome +33.0 (n=1)
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How did it go? (-100 worst, +100 best)
- generally surprisingly well!
Monitoring
Relevant anecdote
⚕️ Provider 0
Fluoxetine is great for getting off other SxRIs! Especially venlafaxine and duloxetine.
Relevant Literature
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See also
References
Summary
Classes
SSRI, Anxiolytic, Antidepressant
Common uses
- Premature ejaculation2.1n=2
- Anxiety disorders broadly1.5n=2
- Panic disorder1.5n=2
- Depressive disorders1.1n=1
- Embarrassment0.5n=3
Pharmacy
Starting dose
10 mg
Preparations
10 mg, 20 mg, 40 mg caps
US FDA Max
40 mg/d