In brief
Sertraline (Zoloft) and escitalopram (Cipralex) are the two most prescribed antidepressants. They belong to one group and work the same way.
Which is better. Neither. In the largest comparison escitalopram came out slightly ahead, and both are tolerated equally well. The gap between the drugs is smaller than the gap between people.
What decides the choice. Your heart, your gut and your other medicines. That is what follows.
How they work
Serotonin carries a signal between nerve cells. Once released it is not used up: a pump takes it back. Both drugs partly close that pump, so serotonin stays in play longer.
Picture a sink draining too fast. You can open the tap wider, or you can plug the drain. These drugs are the plug.
Why the effect is not immediate. The pump is blocked within hours, but mood shifts after three or four weeks. It is not serotonin itself but the slow rewiring it triggers. Expecting a result on day three is pointless — and that is the commonest reason treatment is abandoned before it has begun.
The main difference: heart and gut
If you remember one thing from this piece, let it be this.
Escitalopram has a slightly clearer effect on heart rhythm. It shows dose-dependent lengthening of the QT interval, the measure cardiologists watch. So in older patients, in heart disease and alongside other rhythm-affecting drugs, its dose is capped. No such effect was found for sertraline.
Sertraline troubles the gut more often. Diarrhoea and nausea are noticeably more common with it. For someone with a sensitive stomach, that settles the matter.
Hence a simple rule: heart — sertraline; stomach — escitalopram.
Doses
Their milligrams are not comparable — rather like comparing grams of salt with grams of sugar in a recipe.
▸ Sertraline: usually starts at 50 mg, working range 50–200 mg a day.
▸ Escitalopram: starts at 10 mg, working range 10–20 mg a day.
▸ The effect is judged after 4–6 weeks at the dose reached — for both.
The practical difference is headroom: sertraline has somewhere to grow, escitalopram has a lower ceiling set by cardiac safety.
In anxiety, treatment starts at half the dose: the first days on any of these drugs can briefly increase anxiety. That is an expected phase, not a sign the drug is wrong.
📄 The comparison in tables — efficacy, doses and side effects side by side on a single page: download the PDF. Easy to print and take to an appointment.
How the choice is made
Sertraline is the likelier choice with heart disease or QT prolongation, when depression developed on top of another illness, when treatment is planned for the long term, or when dose headroom matters.
Escitalopram is the likelier choice when a simple regimen matters, when gastrointestinal effects are poorly tolerated, or after an unsuccessful trial of sertraline.
And the most honest one: if one of them has helped this person before, that is usually the one to return to. Personal history outweighs any ranking.
About stopping — the most important part
If only one paragraph stays with you, let it be this one.
Never stop abruptly. In roughly a third of people, stopping brings dizziness, «brain zaps», nausea, irritability and poor sleep. The dose is lowered gradually, to a plan from your doctor.
But this is not addiction. Antidepressants create no craving, demand no rising dose for the same effect and produce no high. The body has simply adapted to a new signal level and needs time to adapt back. Confusing the two makes thousands of people refuse treatment they need every year.
What to tell your doctor
▸ Sexual difficulties — lower desire, delayed orgasm. They occur with both drugs and are solved by changing the drug, the dose or the schedule. Silence usually ends in stopping without warning.
▸ Emotional blunting — when the capacity for joy left along with the sadness. Also worth raising.
▸ Every other medicine you take, painkillers and herbal remedies included: this group interacts more often than people expect.
Who they are not for
▸ Anyone taking MAO inhibitors — a washout period is needed between courses.
▸ Bipolar disorder without a mood stabiliser in place.
▸ Adolescents and young adults — only under close monitoring in the first weeks.
▸ In pregnancy and breastfeeding the decision is made separately.
The short version
▸ Both drugs are well tolerated — the key point for anyone afraid to start.
▸ Heart — sertraline; stomach — escitalopram.
▸ Judge the effect after a month, not after three days.
▸ Never stop abruptly — the tapering plan is the doctor’s to write.
▸ A doctor makes the choice, not a table: these are prescription drugs and the fit depends on your health as a whole.
On prescribing. Both drugs are prescription-only. If you need to work through your own case — which one fits, how to reach the right dose, what to do about side effects and how to come off safely — that is what a consultation is for.
Sources
1. Cipriani A, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder. Lancet. 2018;391(10128):1357–1366. PMID 29477251
2. Cipriani A, et al. Sertraline versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2009;(2):CD006117. PMID 19370626
3. Castro VM, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ. 2013;346:f288. PMID 23360890
4. Henssler J, et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry. 2024;11(7):526–535. PMID 38851198
5. Kishi T, et al. Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase. Mol Psychiatry. 2023;28(1):402–409. PMID 36253442
