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Fluoxetine

From Pharmacopedia
Revision as of 22:51, 14 May 2026 by MDElliottMD (talk | contribs) (Pharmacopedia: approved experience contribution)
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.

Experience

πŸ‘₯ No personal reports yet
βš• 1 provider report Β· avg efficacy 40.0/100 Β· avg side-effect burden 40.0/100 Β· 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>

<indication ref="premature-ejaculation"/>

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Titration 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).

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Effects

  • AnxiolysisπŸ‘€ no reports yetβš•οΈ ~33% +67.0 (n=1)
    Classically starting at 3–4 weeks and improving for another 8–12.
  • Delayed orgasm/ejaculationπŸ‘€ 0% β€” (n=3)βš•οΈ ~80% +33.0 (n=1)
  • Mood enhancementπŸ‘€ no reports yetβš•οΈ ~5% +67.0 (n=1)
  • NauseaπŸ‘€ no reports yetβš•οΈ ~5% -33.0 (n=1)
    Common, often improves over 1–2 weeks.
  • Decreased libidoπŸ‘€ no reports yetβš•οΈ ~33% -100.0 (n=1)
  • Temporary erectile dysfunctionπŸ‘€ no reports yetβš•οΈ ~20% -67.0 (n=1)
  • Persistent Sexual DysfunctionπŸ‘€ no reports yetβš•οΈ ~0% -100.0 (n=1)
    Historically associated with SSRIs.
AnorgasmiaπŸ‘€ no reports yetβš•οΈ ~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.[3]

Monitoring

None required

Relevant anecdote

βš•οΈ Provider by MDElliottMD0
Fluoxetine is great for getting off other SxRIs! Especially venlafaxine and duloxetine.

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Relevant Literature

No literature entries yet.

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See also

Sertraline, Duloxetine

References

  1. ↑ https://pmc.ncbi.nlm.nih.gov/articles/PMC9666396/
  2. ↑ https://www.ncbi.nlm.nih.gov/books/NBK501186/
  3. ↑ 3.0 3.1 3.2 https://www.ncbi.nlm.nih.gov/books/NBK459223/ Cite error: Invalid parameter "pk_elimination" in <ref> tag. The supported parameters are: dir, follow, group, name.
Structure of Fluoxetine
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
+ 3 more uses β†’
Pharmacy
Starting dose
10 mg
Preparations
10 mg, 20 mg, 40 mg caps
US FDA Max
40 mg/d
Pharmacology
Routes
Oral
Duration
Very long
Half-life
1–4 days (7–15 days for norfluoxetine)
Bioavailability
70–90% (oral)
Pregnancy
Category C[2]
Legal status
Rx-only in US
Purported mechanism
TrkB/BDNF[1] Fluoxetine is a selective serotonin reuptake inhibitor.0