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Sertraline

Sertraline

Zoloft Lustral Apo-Sertral Asentra Gladem

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Updated: December 06, 2025

Overview

Sertraline is a selective serotonin reuptake inhibitor (SSRI) antidepressant first approved by the FDA in 1991. It is widely prescribed for major depressive disorder and various anxiety disorders, with efficacy demonstrated across multiple randomized controlled trials. As one of the most commonly prescribed antidepressants, sertraline exhibits favorable tolerability compared to older antidepressants. Its side effect profile typically includes gastrointestinal symptoms and sexual dysfunction, though these are generally less severe than with tricyclic antidepressants.

Drug Class

Therapeutic Category: • Antidepressant Pharmacologic Class: • Selective Serotonin Reuptake Inhibitor (SSRI) • Psychotherapeutic Agent

Mechanism of Action

Sertraline potently inhibits presynaptic serotonin reuptake transporters (SERT) in the central nervous system, increasing synaptic serotonin concentrations. It has minimal effects on norepinephrine and dopamine reuptake. At therapeutic doses, sertraline binds to sigma-1 receptors and inhibits dopamine transporters, though the clinical significance remains unclear. Chronic administration leads to adaptive changes in serotonin receptor sensitivity and downstream neurotransmission.

Pharmacokinetics

Absorption: Slow and complete absorption with 6-8 hour Tmax. Food increases bioavailability by 25%. Distribution: 98% protein bound (primarily to albumin). Apparent volume of distribution is approximately 20 L/kg. Metabolism: Extensive hepatic metabolism via CYP2B6, CYP2C9, CYP2C19, and CYP3A4 to N-desmethylsertraline (weakly active). Exhibits nonlinear pharmacokinetics at higher doses. Excretion: 40-45% renal excretion (12-14% unchanged), 40-45% fecal elimination. Half-life: 26 hours (parent drug); 62-104 hours (metabolite)

Pharmacodynamics

Primary Effects: • Increased synaptic serotonin (5-HT) levels • Downregulation of 5-HT1A autoreceptors • Enhanced serotonergic neurotransmission Clinical Effects: • Mood improvement (2-4 week onset) • Anxiety reduction • Obsessive-compulsive symptom control • Antipanic effects

Indications

• Major Depressive Disorder (MDD): Treatment of acute episodes and maintenance therapy • Obsessive-Compulsive Disorder (OCD): Adult and pediatric patients (age 6+) • Panic Disorder: With or without agoraphobia • Post-Traumatic Stress Disorder (PTSD) • Premenstrual Dysphoric Disorder (PMDD) • Social Anxiety Disorder (Social Phobia)

Contraindications

Absolute: • Concurrent MAOI use or within 14 days of discontinuation • Known hypersensitivity to sertraline • Pimozide coadministration Relative: • History of seizure disorder • Bipolar disorder (risk of manic switch) • Uncontrolled angle-closure glaucoma

Dosage & Administration

Major Depressive Disorder/OCD/Panic Disorder/PTSD/Social Anxiety Disorder: • Initial: 50 mg once daily • May increase by 50 mg increments at ≥1 week intervals • Maximum: 200 mg daily PMDD: • Continuous dosing: 50 mg daily • Luteal phase dosing: 50 mg daily starting 14 days before menses Pediatric OCD (6-12 years): • Initial: 25 mg daily • May increase to 50 mg daily after 1 week • Maximum: 200 mg daily

Special Populations

Pediatric: Only approved for OCD ≥6 years. Monitor for suicidality. Geriatric: Initiate at 25 mg daily. Increased sensitivity to hyponatremia. Renal impairment: No dose adjustment needed in mild-moderate impairment. Use caution in severe impairment. Hepatic impairment: Reduce dose by 50% in Child-Pugh A/B cirrhosis. Contraindicated in hepatic failure.

Adverse Effects

Common (>10%): • Nausea (26%) • Diarrhea (20%) • Insomnia (20%) • Dry mouth (14%) • Sexual dysfunction (15% males, 2% females) Serious (<1%): • Serotonin syndrome • QT prolongation • Severe hyponatremia (SIADH) • Suicidal ideation (black box warning) • Bleeding risk (especially with anticoagulants)

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated) • Warfarin: Increased INR and bleeding risk • CNS depressants: Additive sedation • Triptans: Increased serotonin syndrome risk • CYP2D6 substrates: Increased concentrations of drugs like desipramine • NSAIDs/antiplatelets: Increased bleeding risk

Warnings & Precautions

• Black Box Warning: Suicidal ideation/behavior in children/adolescents/young adults • Serotonin Syndrome: Monitor for hyperthermia, rigidity, autonomic instability • QT Prolongation: Avoid in congenital long QT syndrome • Discontinuation Syndrome: Taper gradually • Activation: Monitor for anxiety/agitation early in treatment • Bleeding Risk: Caution with anticoagulants/antiplatelets

Pregnancy & Lactation

Pregnancy: FDA Category C. Third trimester exposure associated with neonatal complications (respiratory distress, feeding difficulties). Potential persistent pulmonary hypertension (PPHN) risk (RR 2.5). Lactation: Excreted in breast milk (maternal plasma:milk ratio 2:1). AAP considers compatible with breastfeeding. Monitor infant for irritability/feeding issues.

Monitoring Parameters

• Mental status/suicidal ideation (especially first 3 months) • Mood and anxiety symptoms • Serum sodium (in elderly/diuretics users) • Liver function tests (in hepatic impairment) • ECG in patients with cardiac risk factors • Bleeding signs in high-risk patients • Height/weight in pediatric patients

Patient Counseling

• Take once daily (morning or evening) with/without food • Therapeutic effect may take 2-4 weeks • Do not abruptly discontinue • Report unusual bleeding/bruising • Avoid alcohol • Use contraception (potential fetal risk) • Report worsening anxiety/agitation • Caution with driving/operating machinery

Storage & Stability

Store at 20-25°C (68-77°F). Protect from light. Keep in original container with desiccant. Stable in oral concentrate for 24 months when undiluted; when diluted, use within 6 months.

Clinical Pearls

• Start low (25 mg) in anxious patients to minimize activation • GI side effects often improve with continued treatment • Consider bedtime dosing if sedation occurs • For sexual dysfunction: Dose reduction or weekend holidays may help • Therapeutic drug monitoring not routinely indicated • Half-life allows once-daily dosing despite multiple daily metabolites

References

• UpToDate: Sertraline Drug Information (2023) • FDA Prescribing Information: Zoloft (2022) • Stahl SM. Essential Psychopharmacology (2021) • Hirsch M, et al. JAMA. 2019;322(15):1516-1525 • Cipriani A, et al. Lancet. 2018;391(10128):1357-1366