BLACK BOX WARNING
- suicidal thinking and behavior in pediatric and young adult patients
sertraline
Brand: Zoloft
⚠ BBW Prototype: fluoxetine
Drug Class: antidepressant
Drug Family: antidepressant
Subclass: SSRI
Organ Systems: cns
Mechanism of Action
Selective SERT inhibitor with mild dopamine transporter inhibition; fewer CYP interactions than fluoxetine; also has modest sigma receptor activity.
serotonin reuptake transporter (SERT)
Indications
- major depressive disorder
- PTSD
- OCD
- panic disorder
- social anxiety disorder
- premenstrual dysphoric disorder
Contraindications
- concurrent MAOIs
- concurrent pimozide
- disulfiram (oral concentrate contains alcohol)
Adverse Effects
Common
- nausea (especially initially)
- diarrhea
- insomnia
- sexual dysfunction
- dry mouth
- dizziness
Serious
- serotonin syndrome
- suicidal ideation
- hyponatremia
- QTc prolongation
- abnormal bleeding
Pharmacokinetics (ADME)
| Absorption | Bioavailability ~44%; food increases absorption of oral concentrate |
| Distribution | Highly protein-bound (98%); Vd ~20 L/kg |
| Metabolism | CYP2C19, CYP2C9, CYP2D6, CYP3A4 to inactive N-desmethylsertraline |
| Excretion | Fecal (~44%) and renal (~40%) |
| Half-life | 22–36 hours |
| Onset | 1–2 weeks (partial); 4–6 weeks (full antidepressant effect) |
| Peak | 4.5–8.4 hours |
| Duration | 24 hours |
| Protein Binding | 98% |
| Vd | ~20 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | serotonin syndrome | major |
| NSAIDs/anticoagulants | additive bleeding risk via platelet serotonin depletion | moderate |
| pimozide | QTc prolongation via CYP2D6 inhibition at higher sertraline doses | major |
Nursing Considerations
- Monitor suicidal ideation in first 4 weeks; schedule follow-up within 1 week of initiation
- Take with food to reduce GI side effects, especially nausea in the first 1–2 weeks
- Monitor serum sodium (particularly in elderly patients on diuretics) — hyponatremia/SIADH can occur
- Advise patients that full antidepressant effect takes 4–6 weeks; do not discontinue prematurely if initial response seems limited
Clinical Pearls
- Sertraline has the most extensive safety data in pregnancy of all SSRIs and is often the preferred SSRI during pregnancy — though all SSRIs carry neonatal adaptation syndrome risk
- Among SSRIs, sertraline is considered to have the fewest drug interactions because it has the least potent CYP inhibitory profile at standard doses
Safety Profile
Pregnancy safe
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.