Zoloft
Zoloft
Generic Name
Zoloft
Mechanism
- Selective inhibition of serotonin (5‑HT) reuptake by blocking the serotonin transporter (SERT) in presynaptic neurons.
- ↑ Synaptic 5‑HT concentration → enhanced stimulation of postsynaptic serotonin receptors.
- Minimal activity at other monoamine transporters (dopamine, norepinephrine) and minimal anticholinergic, alpha‑adrenergic, or histaminergic effects.
- Steady‑state plasma levels ≈ 5‑10 µg/mL associated with therapeutic response.
Pharmacokinetics
- Absorption: 100 % bioavailable, peak plasma 4–6 h post‑dose.
- Distribution: 1.7 L/kg; 74 % plasma protein binding (primarily albumin).
- Metabolism: Primarily hepatic via CYP2B6, CYP3A4, CYP2C19 (→ N‑desmethyl‑sertraline).
- Elimination: 80 % renal (≈ 46 % unchanged, 34 % metabolite), 20 % fecal.
- Half‑life: 24–36 h; steady state ≈ 4 days.
- Drug interactions: Strong inhibitors/inducers of CYP2B6 or CYP3A4 (e.g., ketoconazole, rifampin) alter plasma levels.
Indications
- Major depressive disorder (MDD)
- Generalized anxiety disorder (GAD)
- Social anxiety disorder (SAD)
- Obsessive‑compulsive disorder (OCD)
- Post‑traumatic stress disorder (PTSD)
- Premenstrual dysphoric disorder (PMDD)
Contraindications
- Contraindications:
- Concomitant monoamine oxidase inhibitor (MAOI) therapy or within 14 days of last MAOI.
- Active use of CYP2B6 or CYP3A4 inhibitors in the setting of high‑dose SSRI therapy.
- Warnings:
- Serotonin syndrome with concomitant serotonergic agents.
- Suicidal ideation in adolescents/young adults; monitor closely.
- Hyponatremia (SIADH), especially in elderly.
- QTc prolongation minimal but caution in patients with congenital long QT or on other QT‑prolonging drugs.
Dosing
| Indication | Starting Dose | Titration | Max Dose | Form | Administration |
| MDD/GAD/OSD/PTSD | 25 mg PO daily | ↑25 mg/week (to 50 mg) | 200 mg/day | Tablet, XL | Morning or bedtime |
| OCD/PMDD | 25 mg PO daily | ↑25 mg/2‑4 wk (to 50 mg) | 200 mg/day | Tablet | Morning |
• Extended‑release (XL): take on empty stomach; may be swallowed whole.
• Drug holidays: typically not advised; taper over ≥ 2 weeks if discontinuation necessary.
Monitoring
| Parameter | Frequency | Rationale |
| Serum creatinine/eGFR | Baseline, then < 5 years | Renal clearance of metabolites |
| Electrolytes (Na⁺, K⁺) | Baseline, then 4–6 wk if symptomatic | Hyponatremia risk |
| Mental status | Every 2–4 wk in first 2 mo | Suicide risk, efficacy |
| QTc | Baseline if known QT‑prolonging exposure | Rare risk of arrhythmia |
| Weight & BP | Every visit | Metabolic effects |
Clinical Pearls
- Rapid Responder Tip: About 25 % of patients with OCD will show ≥ 35 % reduction in Y‑BOCS by Week 4; consider early dose escalation in responders.
- Sexual Dysfunction: 20‑30 % of patients experience issues. Use short‑acting SSRIs (e.g., paroxetine) in a “drug holiday” around intercourse or add low‑dose dopamine agonist as adjunct.
- Discontinuation Syndrome: Mild symptoms can appear at 2–4 wk off‑therapy. Taper over ≥ 2 weeks (25 mg every 5–7 days).
- Drug Interactions: Avoid co‑administration with St. John’s wort (serotonin enhancer) to reduce risk of toxicity.
- Elderly Considerations: Initiate at 25 mg; weigh risk of hyponatremia and falls.
- Pediatric Use: FDA-approved 6‑year‑olds for ODD; dose starts at 12.5 mg/day, titrate to 50 mg over 4 weeks.
> Takeaway: Zoloft is a versatile SSRI with a favorable safety profile, but requires vigilant monitoring for serotonergic effects, renal status, and mood changes—particularly in adolescents and the elderly.