SSRIs

Selective serotonin reuptake inhibition at SERT; weeks-long receptor adaptation delivers the clinical effect.

Members

SertralineA first-line SSRI with a clean interaction profile and a mountain of indications.EscitalopramThe cleanest SSRI for interactions, with a dose ceiling set by the QT interval.FluoxetineThe SSRI with a half-life so long it tapers itself, and inhibits half the CYP2D6 in the room.

Also in this class: Escitalopram (cleanest, QT at high dose) · Fluoxetine (longest half-life, self-tapering) · Paroxetine (short, anticholinergic, worst discontinuation) · Citalopram (QT ceiling). Full pages arrive as the library grows.

Compare the members

Drug	Half-life	CYP2D6 inhibition	Distinguishing point
Sertraline	~26 h	Mild	First-line default; diarrhea early
Escitalopram	27 to 32 h	Minimal inhibition	Cleanest interaction profile; dose-dependent QT
Fluoxetine	4 to 6 days, metabolite longer	Potent CYP2D6 inhibitor	Self-tapering, which is why stopping it is easy

Sertraline

Half-life: ~26 h
CYP2D6 inhibition: Mild
Distinguishing point: First-line default; diarrhea early

Escitalopram

Half-life: 27 to 32 h
CYP2D6 inhibition: Minimal inhibition
Distinguishing point: Cleanest interaction profile; dose-dependent QT

Fluoxetine

Half-life: 4 to 6 days, metabolite longer
CYP2D6 inhibition: Potent CYP2D6 inhibitor
Distinguishing point: Self-tapering, which is why stopping it is easy

Shared across the class

Indications: Depression · Anxiety disorders · OCD · PTSD
Adverse effects: Early GI upset · Sexual dysfunction · Sleep changes · Hyponatremia in older adults · Bleeding tendency · Serotonin syndrome in combinations
Contraindications: MAO inhibitors within 14 days
Monitoring: Mood/anxiety response at 2-4 weeks · Early activation and safety · Sodium in symptomatic older adults

What makes each agent different

Half-life politics: fluoxetine barely needs a taper; paroxetine and venlafaxine punish missed doses.
QT: citalopram and escitalopram carry dose ceilings.
Interactions: fluoxetine and paroxetine are strong 2D6 inhibitors (tamoxifen!); sertraline and escitalopram are cleaner.

Choosing an SSRI is mostly choosing a half-life and an interaction profile; efficacy differences are small.

Last reviewed 2026-08-15 · Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed.