Antidepressant withdrawal: When and how to taper antidepressants

Antidepressants can be a powerful treatment for depression and anxiety, and they often work best together with talk therapy, which helps people build coping skills and address the causes of their distress. Once you feel better, you may think about stopping your antidepressant. This is a decision to make carefully, together with your doctor, nurse practitioner or pharmacist. Many people have trouble stopping because of withdrawal symptoms, renewed anxiety or a return of depression. This article explains why withdrawal happens, which antidepressants are harder to stop, and how to taper safely.

What is antidepressant withdrawal?

Antidepressant withdrawal (also called discontinuation symptoms) can happen when you stop an antidepressant or lower the dose. Over months of treatment, the brain adapts to the medication, and it needs time to readjust when the medication is reduced. Common symptoms include:

• dizziness, light-headedness and nausea
• trouble sleeping and vivid dreams
• irritability, anxiety and mood swings
• flu-like feelings, such as tiredness and aches
• unusual sensations, such as electric "brain zaps"
• intense inner restlessness (akathisia)

Symptoms usually start within a few days of stopping or lowering the dose. For most people they are mild and pass within a few weeks, but for some they are severe or last much longer.

How common is antidepressant withdrawal?

Estimates vary. A 2024 meta-analysis of 79 studies and more than 21,000 patients found that about 31% of people had at least one discontinuation symptom after stopping an antidepressant. Because 17% of people who stopped a placebo also reported symptoms, the researchers estimated that about 1 in 6 to 7 people have symptoms caused by stopping the medication itself. Severe symptoms affected about 3%. The University of British Columbia's Therapeutics Initiative, drawing on other studies and patient surveys, estimates that at least half of people notice some withdrawal symptoms. Either way, withdrawal is common enough that every plan to stop an antidepressant should include a slow taper.

The risk is higher for people who have taken an antidepressant for a long time or at a higher dose, and for some medications more than others.

Which antidepressants are harder to stop?

The most important factor is the drug's half-life, which is how long it takes the body to clear half of the medication. Drugs with a short half-life leave the body quickly, so blood levels drop sharply when a dose is reduced or missed. Drugs with a long half-life, such as fluoxetine, taper themselves naturally and are less likely to cause withdrawal. In the 2024 meta-analysis, desvenlafaxine, venlafaxine, imipramine and escitalopram were linked to more frequent symptoms, and imipramine, paroxetine and venlafaxine or desvenlafaxine to more severe symptoms.

The table below summarizes the withdrawal risk of common antidepressants, based on their half-life and available studies. Individual experience varies.

Drug name	Risk of withdrawal	Drug class	Main metabolizing enzymes
Paroxetine	Higher	SSRI	CYP2D6
Venlafaxine	Higher	SNRI	CYP2D6, CYP2C19
Desvenlafaxine	Higher	SNRI	Minimal CYP involvement
Duloxetine	Higher	SNRI	CYP1A2, CYP2D6
Levomilnacipran	Higher	SNRI	Mostly eliminated by the kidneys; CYP3A4
Fluvoxamine	Higher	SSRI	CYP2D6, CYP1A2
Mirtazapine	Higher	NaSSA	CYP1A2, CYP2D6, CYP3A4
Citalopram and escitalopram	Moderate	SSRI	CYP2C19
Sertraline	Moderate	SSRI	CYP2C19, CYP2B6
Fluoxetine	Lower	SSRI	CYP2D6, CYP2C9
Vortioxetine	Lower	Serotonin modulator	CYP2D6
Trazodone	Lower	SARI	CYP3A4
Bupropion	Unknown	NDRI	CYP2B6

To see how genes affect specific antidepressants, read Comparison of antidepressants' effectiveness and side effects.

What else affects the risk of withdrawal?

• Dose and duration. Higher doses and longer treatment are linked to more withdrawal symptoms.
• Missed doses. With short half-life drugs, even one or two missed doses can cause symptoms.
• Age and health. Older adults and people with liver or kidney disease often clear antidepressants more slowly and may be more sensitive to changes, so they may need smaller steps and closer follow-up.
• Other medications. Starting or stopping another medication or supplement can raise or lower antidepressant levels in the blood, which can feel like withdrawal or a setback.
• Your genes. The CYP2D6, CYP2C19 and CYP2B6 enzymes break down most antidepressants, and your genes determine how active they are. They affect how much medication is in your blood at a given dose. Research has not yet shown that metabolizer status predicts who will have withdrawal, but these results help a pharmacist understand your drug levels when planning dose steps and checking interactions.

Should I stop my antidepressant?

Many people can stop successfully, but stopping carries a real risk of relapse, so it is worth weighing carefully. In the ANTLER trial, people in UK primary care who had been well on an antidepressant for at least nine months were randomly assigned to continue or to taper off. Over one year, 56% of those who stopped had a relapse of depression, compared with 39% of those who continued. In a Cochrane review, stopping abruptly or with short tapers of four weeks or less was linked to a higher risk of relapse than continuing, although the studies may have mistaken some withdrawal symptoms for relapse. Psychological support, such as preventive cognitive therapy, helped many people stop without a higher relapse risk.

Talk with your prescriber about whether now is the right time. Stopping is usually best when you have been well for several months, your life is relatively stable, and you have support in place.

How can I reduce withdrawal symptoms?

Go slowly

Short tapers of two to four weeks, still common in practice, offer little benefit over stopping abruptly. Tapering over several months, and down to doses much lower than the usual starting dose, is more successful in reducing withdrawal symptoms. In general, the slower, the better.

Use a hyperbolic taper

In a standard "linear" taper, the dose is reduced by the same amount at each step, for example 50, 37.5, 25, 12.5 mg and then zero. Brain imaging studies show that the effect of an SSRI on its target, the serotonin transporter, changes very little between high doses but drops steeply at low doses. This is why the last steps of a linear taper are often the hardest.

A hyperbolic taper reduces the dose by a percentage of the current dose, for example about 10% of the most recent dose every two to four weeks. The steps become smaller as the dose gets lower, so the effect on the brain changes more evenly. For high-risk medications such as venlafaxine or paroxetine, a hyperbolic taper can take many months or even a year or more.

Get precise doses

Small doses are hard to get by splitting tablets. Ask your pharmacist about liquid formulations, or about smaller doses specially prepared by a compounding pharmacy. Early research suggests that diluting liquid formulations gives accurate low doses.

Agree on a plan and check in regularly

• Plan the taper with your prescriber and pharmacist before you start.
• Check in every two to four weeks after each dose reduction.
• Agree in advance that you can pause or return to the previous step if symptoms become hard to manage, and when to contact your care team.
• Use a pill organizer or a reminder app. Missed doses and irregular timing can cause sudden drops in blood levels.

Look after your body and mind

Regular physical activity, good sleep habits, mindfulness or meditation, and talk therapy can all help you stay well during and after the taper.

Is it withdrawal or is my depression coming back?

Withdrawal symptoms usually start within days of a dose reduction, often include physical symptoms such as dizziness, brain zaps or flu-like feelings, and improve quickly if you go back to the previous dose. A relapse of depression usually develops more gradually over weeks, and symptoms such as low mood and loss of interest persist. Telling them apart can be hard, so report any changes to your care team rather than deciding alone. If you have thoughts of self-harm, seek help right away.

How can pharmacogenetic testing help?

A Pillcheck test reports CYP2D6, CYP2C19 and CYP2B6, the main genes that affect antidepressant levels. A pharmacist can use your results together with your full medication list to plan dose steps, check for interactions with other medications, and help choose a well-tolerated medication if you need to restart or switch treatment. Read more about how genes affect antidepressant side effects and how to reduce the risks of antidepressants.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• Withdrawal symptoms are common when stopping an antidepressant. Estimates range from about 1 in 6 people to half or more, and about 3% have severe symptoms.
• Antidepressants with a short half-life, such as paroxetine and venlafaxine, are harder to stop. Fluoxetine, with its long half-life, is among the easiest.
• Stopping increases the risk of relapse, so decide together with your prescriber, ideally when you have been well for several months.
• Slow, hyperbolic tapering over months, with precise low doses from liquid or compounded formulations, reduces withdrawal symptoms.
• Check in every two to four weeks, and agree in advance that you can pause or go back a step.
• Pharmacogenetic results and a pharmacist review help plan dose steps, check interactions and guide the choice of medication if treatment needs to restart.

Frequently asked questions

How long should an antidepressant taper take?

It depends on the medication, the dose and how long you have taken it. Many people need several months, and some need a year or more, especially with paroxetine or venlafaxine. Short tapers of two to four weeks often do not prevent withdrawal.

Can I stop my antidepressant once I feel better?

Talk to your prescriber first. Stopping too soon or too quickly raises the risk of withdrawal and relapse. Guidelines generally recommend continuing for at least six months after you feel well, and longer if you have had several episodes of depression.

What should I do if withdrawal symptoms are hard to manage?

Contact your prescriber or pharmacist. Going back to the previous dose usually eases withdrawal symptoms within days, and you can then continue with smaller steps.

Can a genetic test tell me how fast to taper?

Not on its own. A pharmacogenetic test shows how quickly your body breaks down many antidepressants, which helps your pharmacist understand your drug levels and check interactions. The pace of the taper is still guided by how you feel at each step.

References

Therapeutics Initiative, University of British Columbia. How to stop antidepressants. Therapeutics Letter 157. 2025.

Henssler J, Schmidt Y, Schmidt U, et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry. 2024;11(7):526-535.

Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry. 2019;6(6):538-546.

Van Leeuwen E, van Driel ML, Horowitz MA, et al. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database Syst Rev. 2021;4(4):CD013495.

Duffy L, Clarke CS, Lewis G, et al. Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess. 2021;25(69):1-62.

O'Brien D, Healy AM, Harkin A, Cadogan C. A systematic review of manipulations to pharmaceutical dosage forms used in psychotropic tapering plans. Br J Clin Pharmacol. 2025;91(7):1899-1913.