SSRIs · Psychiatry
Fluoxetine
Prozac®(brand names vary by market)
The SSRI with a half-life so long it tapers itself, and inhibits half the CYP2D6 in the room.
Also: tablet, oral liquid
Mechanism
Selective serotonin reuptake inhibitor with an active metabolite, norfluoxetine, whose half-life is measured in weeks.
Open the interactive pathwayIndications
- Major depressive disorder
- Obsessive-compulsive disorder
- Bulimia nervosa
- Panic disorder
- Depression in adolescents, where it has the best evidence
Formulations
Dosing concepts
Stopping
Its long half-life means discontinuation symptoms are rare and a formal taper is often unnecessary. That is a genuine advantage for a patient who forgets doses.
Switching
Because norfluoxetine persists for weeks, a washout is needed before starting an MAO inhibitor, and interactions continue long after the last capsule.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~72%
- Half-life
- 4 to 6 days; norfluoxetine 4 to 16 days
- Elimination
- hepatic: Potent CYP2D6 inhibitor: it raises levels of metoprolol, some antipsychotics, tamoxifen and codeine's activation is blocked
- Protein binding
- ~95%
Adverse effects
- Insomnia and agitationcommonThe most activating of the SSRIs, which suits some patients and ruins sleep for others.
- Nauseacommon
- Sexual dysfunctioncommon
- Hyponatremiaserious
- Weight loss early, then neutralcommon
Contraindications & precautions
Contraindications
- Concurrent or recent MAO inhibitor
- Concurrent pimozide or thioridazine
Precautions
- Bipolar disorder
- Concurrent CYP2D6-dependent drugs
- Bleeding risk with NSAIDs or anticoagulants
Interactions
- SSRIs / SNRIs + MAO inhibitors (including linezolid)avoidSerotonin syndrome: agitation, clonus, hyperthermia: potentially fatal.
- SSRIs / SNRIs + TramadolcautionSerotonin syndrome (usually milder spectrum) and seizures, especially at higher doses or in the elderly.
- SSRIs + NSAIDs / anticoagulantsmonitorUpper GI bleeding risk roughly doubles versus either alone.
Monitoring
Mood and suicidality
Especially in adolescents, where it is nonetheless the best-evidenced agent · Early and repeatedly
Sleep
Its activating profile
Interacting medicines
CYP2D6 inhibition persists for weeks after stopping
Counselling points
- Take it in the morning; it can keep you awake.
- It stays in the body for weeks, so if you stop, the effects and interactions fade slowly.
- Tell any prescriber you take this, even a few weeks after stopping.
- Give it four to six weeks before judging it.
Clinical pearls
- Fluoxetine blocks CYP2D6, which is the enzyme that converts codeine and tramadol into their active forms. A patient on both gets no analgesia and cannot explain why.
- In a woman on tamoxifen, a potent CYP2D6 inhibitor reduces conversion to the active metabolite. It is one of the few interactions where the harm is measured in cancer outcomes.
References & review
- Fluoxetine product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.