Antidepressant half-life An antidepressant’s half-life is the time it takes for the amount of the drug in your blood to fall by half. It shapes how soon, and how likely, withdrawal symptoms are after a missed dose or a cut. For some drugs, such as fluoxetine, what the drug turns into in the body lasts longer still. Half-life is only part of the picture, so withdrawal can still happen with longer-acting drugs.
Also called: Half-life.
Written by Alena Kozlova, PhD , from published studies and prescribing information.
Definition medically reviewed by Dr. Jason Tan , Consultant Psychiatrist, on October 28, 2026, this definition only. Next review: October 28, 2027.
What is a half-life of a drug? It is the time for the drug’s concentration in the blood to fall by half. The body clears each medication mostly by breaking it down in the liver and passing what is left out through the kidneys. Each drug is broken down at a different speed, so half-lives range from about an hour to several days. The speed also differs between people, with age, liver or kidney disease, genes and other medicines. For example, the Lexapro prescribing information reports a half-life about 50% longer in people over 65. So the figures quoted are averages.
How long does an antidepressant stay in your system? After one half-life, half of the drug is left; after two, a quarter; after three, an eighth. On average it takes about five half-lives for a drug to clear: by then around 97% of it has gone. Some antidepressants also break down into active substances that last longer than the drug itself. Venlafaxine itself has a half-life of about 5 hours, but the active substance it turns into lasts about 11, so the two together take two to three days to clear. A drug with a half-life of about a day takes around five days, and fluoxetine takes several weeks.
Which antidepressants have the shortest and longest half-lives? Among the 18 antidepressants sold in the US in the table below, venlafaxine has the shortest half-life, about 5 hours, though the active substance it turns into lasts about 11. Fluoxetine has the longest, 4 to 6 days with regular use by its US prescribing information, and norfluoxetine, which fluoxetine breaks down into, lasts 4 to 16 days. Vortioxetine comes next, at close to 3 days.
Does a longer half-life mean easier withdrawal? Often milder, but not always: half-life is only one factor. A short half-life means the level drops fast after a missed dose or a cut, and UK guidance from NICE names venlafaxine and paroxetine as more likely to cause withdrawal. Yet paroxetine’s half-life, about 21 hours, is close to that of other SSRIs, so other properties of a drug matter too. A long half-life delays and softens the drop. Withdrawal can still happen with fluoxetine, sometimes weeks after the last dose.
Half-life by antidepressant Half-lives of antidepressants sold in the US, shortest first.
Why does half-life matter for a taper? With a short half-life, a step down is felt within a day or two, so problems show up quickly and the next step can be adjusted. With fluoxetine, a step can take weeks to be felt fully, so prescribers usually wait longer before judging how it went.
What people on Reddit say
On the forums for two short half-life medications, symptoms came within a day more often: 15 of 39 people on r/effexor and r/cymbalta, against 19 of 83 overall. Of 1,185 people who described coming off an SSRI or SNRI on Reddit, 83 said how soon symptoms began after a missed dose, a dose cut or their last dose: 19 within a day, 24 within two or three days, 30 only after more than a week, and the other 10 at other times. People who write about coming off are not typical of everyone who stops, so these counts show what happens, not how often.
From public Reddit posts, counted by withClaro. These are self-reports, not a clinical study.
What to do If symptoms come on hard after a missed dose or a step down, contact your prescriber rather than waiting for your next appointment. Ask them what to do if you miss a dose, and how slow the last steps of a taper should be. The guide for your medication in the withClaro taper calculator shows its half-life and usual doses.
Find the taper guide for your medication
How withClaro helps Your doses and symptoms side by side, so it’s easier to see when a late dose is behind them A record you can show your prescriber Get the withClaro app on the App Store
Related terms Sources U.S. Food and Drug Administration. Lexapro (escitalopram) tablets and oral solution: prescribing information. FDA / DailyMed, 2026. U.S. Food and Drug Administration. Celexa (citalopram): prescribing information. FDA / DailyMed, 2023. U.S. Food and Drug Administration. Effexor XR (venlafaxine extended-release capsules): prescribing information. FDA / DailyMed, 2025. U.S. Food and Drug Administration. Paxil (paroxetine) tablets: prescribing information. FDA / DailyMed, 2026. U.S. Food and Drug Administration. Prozac (fluoxetine): prescribing information. FDA / DailyMed, 2026. Gury C, Cousin F. Pharmacokinetics of SSRI antidepressants: half-life and clinical applicability. L'Encéphale, 1999. National Institute for Health and Care Excellence (NICE). Depression in adults: treatment and management. NICE guideline [NG222]. NICE, 2022. Horowitz MA, Taylor D. The Maudsley Deprescribing Guidelines. Wiley, 2024. All glossary terms