Sertraline

ZOLOFT

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Pronunciation: SER-tra-leen (ZOE-loft)

Sertraline ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Sertraline ballicule

Sertraline ZOLOFT mascot mnemonic cartoon — Visual mnemonic: Sertraline mascot
**“So soft on the Shirt line”**
“Baby on Board” → preferred antidepressant during pregnancy
“So soft” → may cause diarrhea and erectile dysfunction

What it isSelective serotonin-reuptake inhibitor; depression, OCD, PTSD and anxiety disorders.

Why this oneIts broad anxiety-spectrum labeling and low interaction burden make it a default SSRI in medical comorbidity.

What limits itEarly diarrhea or nausea and later sexual dysfunction often limit treatment; taper rather than stop abruptly.

Pearls

Preferred SSRI in breastfeeding: low milk levels.
Modestly eases dementia agitation, like citalopram.
Moderate CYP2D6 inhibition at higher doses.
Oral concentrate contains alcohol; avoid with disulfiram.

Sertraline molecular structure (skeletal formula) — Molecular structure: Sertraline

Sertraline prescription history

Animated chart of estimated U.S. prescriptions per year, Antidepressants (1957–2026). Sertraline enters in 1991 (estimated).

FDA-approved for

depression (1991)
OCD (1996)
panic disorder (1997)
PTSD (1999)
PMDD (2002)
social anxiety disorder (2003)

Off-label

premature ejaculation

Classes and tags

Clinical profile

Therapeutic safety burden1 / 4

Overdose danger1 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Legacy pregnancy categoryC

Defining liabilityGI and sexual adverse effects, hyponatremia and additive bleeding risk.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Suicidal thoughts and behaviors — increased risk in pediatric and young adult patients; monitor for worsening and emergent suicidality

FDA dosing	Population	Start	Target	Max
Major depressive disorder (MDD)	Adults	50 mg QD	50-200 mg QD	200 mg/day
Obsessive-compulsive disorder (OCD)	Adults	50 mg QD	50-200 mg QD	200 mg/day
Panic disorder (PD)	Adults	25 mg QD	50-200 mg QD	200 mg/day
Posttraumatic stress disorder (PTSD)	Adults	25 mg QD	50-200 mg QD	200 mg/day
Social anxiety disorder (SAD)	Adults	25 mg QD	50-200 mg QD	200 mg/day
Premenstrual dysphoric disorder (PMDD) — continuous	Adult women	50 mg QD every day of cycle	Increase by 50 mg per menstrual cycle if needed	150 mg/day
PMDD — intermittent (luteal phase only)	Adult women	50 mg QD from 14 days before expected menses through onset of menses; repeat each cycle	Non-responders: next cycle 50 mg QD first 3 days, then 100 mg QD rest of dosing period	100 mg/day (luteal phase)
OCD	Peds 6-12 y	25 mg QD	50-200 mg QD	200 mg/day
OCD	Peds 13-17 y	50 mg QD	50-200 mg QD	200 mg/day

Titration MDD/OCD/PD/PTSD/SAD: increase in 25-50 mg/day steps no more often than once a week; PMDD: increase per menstrual cycle

Renal No adjustment (mild to severe renal impairment)

Hepatic Mild (Child-Pugh 5-6): starting dose and therapeutic range are half the usual; moderate or severe: not recommended

Peds: safety/effectiveness established only for OCD (ages 6-17). Oral solution contains 12% alcohol

Instructions

Tablets: with or without food
Oral solution (20 mg/mL) must be diluted: measure with supplied dropper (25 mg and 50 mg marks only); mix with 4 oz (1/2 cup) water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY; take immediately
Taper gradually when discontinuing
≥14 days between stopping an MAOI and starting, and between stopping Zoloft and starting an MAOI
Screen for personal/family history of bipolar disorder, mania or hypomania before starting

Available strengths

tab 25, 50, 100 mg

Contraindications

MAOIs (concurrently or within 14 days of stopping), incl. linezolid or IV methylene blue — serotonin syndrome
Concomitant pimozide
Oral solution only: concomitant disulfiram (contains alcohol)

Cautions

Suicidal thoughts and behaviors (peds/young adults)
Serotonin syndrome
Increased risk of bleeding
Activation of mania/hypomania
Discontinuation syndrome
Seizures
Angle-closure glaucoma
Hyponatremia/SIADH
False-positive urine benzodiazepine screens
QTc prolongation
Sexual dysfunction

Adverse reactions

Nausea
Diarrhea/loose stool
Tremor
Dyspepsia
Decreased appetite
Hyperhidrosis
Ejaculation failure
Decreased libido

Pregnancy No clear increase in major birth defects; third-trimester exposure risks PPHN and neonatal complications/withdrawal; possible postpartum hemorrhage; oral solution (alcohol) not recommended in pregnancy

Lactation Low levels in human milk; no adverse reactions observed in breastfed infants

Cost

Sertraline (ZOLOFT)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/mo	CostPlus
25 mg	tab	30 qd	$0.87	offered
50 mg	tab	30 qd	$1.04	offered
100 mg	tab	30 qd	$1.52	offered

Generic entry2006

Serotonin and MAOI

Provisional washout figures

SRI significance3 / 4

MAO-A inhibition0 / 4

Serotonin release0 / 4

Elevating mechanismSRI

Non-elevating actionNone recorded

Exposure dependenceTherapeutic exposure; severe toxicity requires meaningful MAO-A inhibition

Washout BEFORE an MAOI14 days

Evidence confidenceHigh

InterpretationClinically significant SRI. A second SRI generally represents therapeutic duplication/additive adverse effects, not the classic life-threatening interaction.

Active metabolites

Desmethylsertraline

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Memory aids: interaction avatars

CYP2D6 inhibitor (weak–moderate)

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Self-check

What makes sertraline useful in medical comorbidity?
Low interaction burden.
How should sertraline be discontinued?
Taper rather than stop abruptly.