Sertraline (Zoloft) is one of the most prescribed antidepressants in the world and the workhorse first-line SSRI in the US for depression, generalised anxiety, panic disorder, social anxiety, OCD, PTSD, and PMDD. If you walk into a GP's office in America with anxiety or depression, this is probably what you'll be offered. It's the SSRI with the broadest set of FDA-approved indications, the best safety profile in pregnancy and breastfeeding, and the cleanest reputation in psychiatry, which is why it's the default choice in women of reproductive age, postpartum, and during pregnancy.

What makes sertraline subtly different from other SSRIs is that on top of blocking serotonin reuptake, it also weakly blocks dopamine reuptake. Whether that's clinically meaningful is debated, but in practice sertraline tends to feel slightly more activating than Escitalopram (Lexapro) and is often the SSRI of choice when fatigue, anhedonia, or low motivation dominate the picture. It's a prescription drug, takes 4-6 weeks to reach full effect, and stopping abruptly can trigger a real withdrawal syndrome. Not a compound to start or stop casually.

Deep-dive

Dosage:

• Standard starting dose: 25-50 mg once daily for depression and GAD. Start at 25 mg for the first week if you're prone to anxiety or panic, then move to 50 mg. The most common therapeutic range is 50-100 mg/day
• OCD: Higher doses are usually needed. Standard is 50 mg to start, titrate to 150-200 mg/day over 4-8 weeks. Off-label use up to 300-400 mg/day exists for treatment-resistant OCD, but the dose-response curve is shallow above 200 mg
• PTSD: Start at 25 mg, titrate to 50-200 mg/day. Average effective dose in trials sits around 100-150 mg
• Panic disorder: Start at 12.5-25 mg for the first 1-2 weeks because SSRIs commonly worsen panic at initiation. Target 50-100 mg/day after settling in
• PMDD: Either continuous 50-100 mg/day or luteal-phase dosing starting 14 days before expected menses and stopping with bleed onset. Luteal-phase dosing has comparable efficacy with less total drug exposure and is genuinely useful for women who don't want continuous SSRI exposure
• Older adults: Start at 25 mg, titrate slowly. Maximum dose is unchanged but tolerability windows narrow. Watch sodium
• Take with food. Sertraline bioavailability increases roughly 25-30% when taken with food, which matters more here than for other SSRIs. Make a habit of taking it with the same meal each day for consistent levels
• Timing: Morning vs evening depends on whether it makes you sleepy or activated. Sertraline is typically slightly activating so most people take it in the morning, but try one for a week and switch if sleep is disrupted
• Time to effect: Anxiety, sleep, and somatic symptoms often improve in 1-2 weeks. Mood and cognitive symptoms take 4-6 weeks. OCD takes 8-12 weeks. Don't judge full response before week 6 (or week 12 for OCD). If there's no movement by then at adequate dose, consider switching or augmenting
• Discontinuation: Never stop abruptly. Sertraline has a 26-hour half-life which puts it in the moderate-risk category for discontinuation syndrome, milder than paroxetine and venlafaxine but worse than fluoxetine. Taper by 25 mg every 2-4 weeks. Hyperbolic tapering (smaller proportional reductions as you get lower) is increasingly recommended after long-term use. The last 12.5-25 mg often cause the most withdrawal symptoms, and liquid sertraline or compounded smaller doses are sometimes needed for the final taper
• Missing a dose: One missed dose isn't a problem. Two or three in a row can trigger discontinuation symptoms because sertraline's half-life is moderate. Set an alarm if you forget regularly
• Alcohol: Not a hard contraindication but the combination amplifies sedation, can blunt the antidepressant effect, and worsens sleep architecture. Moderate use is generally tolerated
• Hard contraindications: MAOIs (14-day washout in either direction), pimozide, linezolid, methylene blue. Combining with serotonergic drugs (other SSRIs/SNRIs, MDMA, tramadol, triptans, dextromethorphan, St John's wort, 5-HTP) raises serotonin syndrome risk
• Drug interactions to know: Tramadol (serotonin syndrome and lowered seizure threshold), NSAIDs and aspirin (increased bleeding risk), warfarin (variable INR effects), QT-prolonging drugs (additive effect, though sertraline is mild here). Sertraline is metabolised by multiple CYP enzymes (mainly 2B6, 2C19, 3A4, 2D6) so it's less prone to single-pathway interactions than fluvoxamine, but it's also a moderate CYP2D6 inhibitor at higher doses