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Zoloft

sertraline

SSRIFDA 1991
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Boxed Warning

Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.

Overview

Sertraline is an SSRI antidepressant approved for major depressive disorder, OCD, panic disorder, PTSD, social anxiety disorder, and premenstrual dysphoric disorder. It is one of the most widely prescribed antidepressants worldwide.

Common Doses

25mg, 50mg, 100mg, 200mg

Formulations

Tablets: 25mg, 50mg, 100mg; Oral concentrate: 20mg/mL

Pregnancy

Category C (risk cannot be ruled out)

Mechanism of Action

Potent and selective inhibitor of serotonin reuptake at the presynaptic membrane (SERT), with minimal effects on norepinephrine and dopamine reuptake. Also has mild affinity for the dopamine transporter.

Taper Notes

Liquid formulation available for precise dosing. Hyperbolic taper recommended.

Maudsley Deprescribing Guidance

Follow hyperbolic reduction schedule. Liquid concentrate (20mg/mL) useful for fine adjustments.

Common Withdrawal Symptoms

brain zapsdizzinessirritabilityinsomniaGI upset

Interactions & Safety

Drug Interactions

  • MAOIs — contraindicated (serotonin syndrome risk)
  • Pimozide — contraindicated
  • Disulfiram — oral concentrate contains alcohol

Food Interactions

  • Food increases peak plasma levels by ~25%
  • Oral concentrate must be diluted before use; avoid mixing with grapefruit juice
  • Avoid alcohol during treatment

Contraindications

  • MAOIs within 14 days
  • Pimozide
  • Disulfiram (oral concentrate contains alcohol)

Toxicity

Serotonin syndrome in overdose or with serotonergic combinations. QT prolongation reported rarely. GI bleeding risk increased with NSAIDs.

Pharmacokinetics

ADME Profile

Absorption

Slowly absorbed after oral administration, Tmax 4.5–8.4 hours. Bioavailability subject to extensive first-pass metabolism. Food increases Tmax slightly.

Distribution

~20 L/kg

Metabolism

Extensive hepatic metabolism primarily via CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 to N-desmethylsertraline (substantially less active).

Elimination

Renal (~40–45% as metabolites) and fecal (~40–45%). Less than 0.2% excreted unchanged in urine.

Protein Binding

~98%

Clearance

~1.5 L/min (oral clearance)

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