Fluoxetine
Fluoxetine is the first SSRI introduced into clinical practice, marketed as Prozac since 1987 and known for its very long half-life and active metabolite. It is used for depression, OCD, bulimia nervosa and premenstrual dysphoric disorder, and is on the WHO Essential Medicines List.
- Chemical formula
- C17H18F3NO
- CAS number
- 54910-89-3
- ATC code
- N06AB03
- Molecular weight
- 309.33 g/mol
- Drug class
- Selective serotonin reuptake inhibitor (SSRI)
- Also known as
- Prozac, Sarafem, Fontex
What is it?
Fluoxetine is the first SSRI to reach clinical use, FDA-approved in 1987 and marketed as Prozac by Eli Lilly. Its launch transformed psychiatric prescribing by offering an antidepressant safer in overdose and easier to tolerate than the tricyclics that preceded it. Authorised generic fluoxetine has been available since 2001 and is widely used; the molecule is on the WHO Essential Medicines List and sits on most major formularies as a first-line SSRI.
Mechanism of action
Fluoxetine selectively inhibits the serotonin reuptake transporter, increasing synaptic serotonin availability. The pharmacologically active metabolite norfluoxetine extends the duration of effect substantially. Therapeutic effect develops over 4–6 weeks. Fluoxetine has the longest half-life of any SSRI, which allows once-daily or even weekly dosing in some forms and largely eliminates the discontinuation syndrome that affects shorter-half-life SSRIs.
Pharmacokinetics
Fluoxetine is well absorbed after oral administration. The terminal half-life of fluoxetine itself is 1–4 days, and of the active metabolite norfluoxetine 7–15 days. Steady state is reached after several weeks. Hepatic metabolism is via CYP2D6, with fluoxetine acting as a strong inhibitor of that enzyme — a clinically important source of drug interactions. The very long half-life means dose changes take weeks to fully manifest.
Indications
Fluoxetine is approved for major depressive disorder (adult and paediatric from age 8), obsessive-compulsive disorder, bulimia nervosa, panic disorder and premenstrual dysphoric disorder. It is the only SSRI with a robust paediatric depression evidence base and FDA paediatric approval. The Sarafem brand markets the same molecule specifically for PMDD; the long-half-life weekly formulation is also available for adherence-challenged adults.
Safety profile
Common adverse effects include nausea, headache, sleep disturbance, sexual dysfunction and reduced appetite. Sexual dysfunction is similar to other SSRIs; weight loss is more common than weight gain. Serotonin syndrome with co-administered serotonergic agents and increased suicidality risk in young adults during initiation are class-effects. The very long half-life means transition to other serotonergic agents requires a several-week washout period.
Products containing this ingredient
Frequently asked questions
Why is fluoxetine called the original SSRI? ▾
Fluoxetine, marketed as Prozac, was the first SSRI to reach clinical use (1987 FDA approval) and the drug that defined the SSRI class. Before fluoxetine, tricyclic antidepressants and MAOIs were standard but had serious tolerability and overdose issues. Fluoxetine\'s launch transformed psychiatric prescribing by offering a safer, easier-to-tolerate antidepressant.
Does fluoxetine need to be tapered? ▾
Fluoxetine\'s very long half-life (1–4 days for the parent, 7–15 days for the active metabolite) means it self-tapers after stopping — discontinuation syndrome is rare and mild. According to clinical practice, fluoxetine can usually be stopped without a structured taper, in contrast to paroxetine or venlafaxine which require careful dose reduction.
Can fluoxetine be used in children? ▾
Yes — fluoxetine is the only SSRI with FDA approval for paediatric major depressive disorder (from age 8) and OCD (from age 7), supported by stronger paediatric evidence than other SSRIs. According to clinical guidelines, fluoxetine is the SSRI of choice when an SSRI is needed in children and adolescents, with regular monitoring for emergent suicidality during initiation.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.