[157] How to stop antidepressants

17 Jul 2025 [157] How to stop antidepressants

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Plain Language Summary

Stopping antidepressants safely

What is this Therapeutics Letter about?

This Therapeutics Letter looks at the problems people may have when they stop taking antidepressant drugs. It talks about how to stop safely, and avoid withdrawal problems.

What are antidepressants used for?

They are medicines (drugs) used to treat depression and other mental health conditions.

Do people always need to keep taking antidepressants?

Not always. Many people start antidepressants during a stressful time but may find that they’ve learned other ways to cope and now feel better, or no longer feel the medication is helping. For many, the negative side effects of the medication might start to outweigh any benefits.

What is antidepressant withdrawal?

Antidepressant withdrawal can happen when someone stops taking antidepressant medication. The body has adjusted to having the drug, and reacts in a negative way while it rebalances and gets used to not having it. It’s a common problem, but many people don’t realize it can happen.

What happens when people stop taking antidepressants?

At least half of the people who stop taking antidepressants will notice some withdrawal symptoms. This can include trouble sleeping, unusual physical sensations, and mood changes. For those taking larger amounts over a long time, symptoms can be quite severe. Some are described as feeling like electric pulses in the head (“brain zaps”) and feelings of extreme physical and emotional restlessness (akathisia).

What does the research recommend for stopping antidepressants?

Experiments are ongoing in Australia to determine the best way to stop. Meanwhile, doctors, nurse practitioners, and pharmacists can help patients stop gradually, sometimes over months or even years, if needed. Stopping slowly can reduce the chance of having severe withdrawal problems. Sometimes, the drug dose is lowered in very small steps, using liquid versions or smaller doses specially made by pharmacists.

How should patients be supported during the stopping process?

Patients should:

  • Be part of the decision to stop.
  • Understand the risks and steps to lower the dose.
  • Be checked every 2-4 weeks after lowering a dose.
  • Feel free to pause or go back a step at their own comfort level.

Why is this important?

Stopping antidepressants the wrong way can cause serious problems. But with careful planning and support, most people can stop safely and feel better in the long run.

Patient Handout

 

How to stop antidepressants

Abstract

Background: Most people treated with antidepressants drugs for mild-to-moderate depression may not benefit from ongoing pharmacotherapy. Over time, adverse effects often outweigh benefits. Yet many, especially women, take antidepressants for much longer than clinical guidelines recommend. Therefore, when prescribers recommend starting an antidepressant, they also need to know how to stop it. Antidepressant withdrawal is a common but under-recognized clinical issue. At least half of people who stop antidepressants experience significant withdrawal symptoms, particularly from higher doses or after long-term treatment.

Aims: Therapeutics Letter 157 discusses the rationale for stopping antidepressants, and provides guidance on safe and effective deprescribing. It recommends dose tapering tailored to a patient’s individual risk, and adjusting an individualized care plan to the clinical response. Successful deprescribing also includes distinguishing withdrawal symptoms from possible relapse of a mental health condition. This Letter offers suggestions from physicians experienced in stopping antidepressants to manage challenging cases such as antidepressant withdrawal-induced akathisia or protracted withdrawal.

Recommendations: To reduce the likelihood or severity of withdrawal symptoms, avoid abrupt discontinuation. For high-risk patients, consider very gradual tapering over months or even years. Hyperbolic dose tapering can be facilitated by liquid formulations or compounding pharmacies. Monitor patients every two to four weeks after each dose reduction, with the option to pause or reverse a dose taper as needed. Patient education, shared decision-making, and informed consent to deprescribing should minimize harms and improve outcomes.

How to stop antidepressants

Vignette: Your new patient is a 53-year-old woman who started venlafaxine 75 mg/day for post-partum depression 19 years ago. Withdrawal symptoms ended a prior attempt to reduce to 37.5 mg/day, suggesting potential problems if she tries again. (See Therapeutics Letter 156, June 2025) But she is now determined to stop the antidepressant. You agree to help her plan an approach more likely to succeed. During a 30-minute follow-up appointment tomorrow, how will you advise her?

Summary and Conclusions

  • At least half of people experience significant withdrawal symptoms when stopping an antidepressant.
  • Prolonged antidepressant treatment and high doses increase the risk of a significant withdrawal syndrome.
  • Some people require months or even years of gentle, supervised dose tapering to minimize disturbing or dangerous symptoms.
  • A compounding pharmacy or use of a liquid formulation or pill/capsule fragments may be necessary for very gradual dose tapers.

Therapeutics Letter 156 (June 2025) updated our understanding of the characteristics and frequency of antidepressant withdrawal syndrome. This Letter focuses on how to avoid or manage what can become a serious clinical problem. The Appendix (available as a sample PDF or editable Word document)  is a modifiable Informed Consent to Taper an Antidepressant form, adapted from opioid and benzodiazepine treatment agreements recommended by the College of Physicians and Surgeons of British Columbia. Allowing patients time to review and consider such a form might facilitate true informed consent and mitigate societal pressures associated with antidepressant withdrawal.

Why stop an antidepressant?

Patients and prescribers have a variety of reasons for wanting to stop an antidepressant. Many people start drug therapy at a stressful period in life, but adjust over time to a loss, or develop non-drug coping skills. Medication may become superfluous.1 For up to 30-50% of people taking antidepressants, no evidence-based reason is found to continue.2–6 Without compelling clinical reasons to continue an antidepressant, it may simply be time to attempt a return to life without medication.

Women are especially likely to receive long-term prescriptions. For example, an Australian longitudinal study on younger women’s health from mid-2012 through 2019 found a mean duration of drug treatment of 2.4 years in women who refilled an initial prescription (N=4,416 born after 1945).7 In contrast, most guidelines recommend 6-12 months of treatment for an episode of anxiety or depression, reserving longer-term treatment for severe and recurrent cases. However, most people who are prescribed antidepressants have mild conditions.8,9

When patients treated with antidepressant drugs improve, it is natural human psychology – but faulty logic – to attribute this with certainty to a pharmacological effect. Most people improve with time alone.10 What appears to be obvious clinical logic should be tempered by understanding that in randomized clinical trials (RCTs), the average difference between antidepressants and placebo is about 2 points on the 52-point Hamilton Depression Rating Scale. And the proportion of participants in randomized controlled trials (RCTs) who achieve clinically meaningful improvement – compared with placebo – varies from a high of about 15% to a low of about 10%.11

This translates to a number needed to treat for clinical benefit (NNT) of about 7-10.12 The large majority would do equally well without an active drug. Even when drug therapy at first seems clearly beneficial, pharmacological tolerance may reduce the effect over time, an inevitable consequence of the brain’s adaptation.13

For many people, adverse effects of antidepressants outweigh benefits. For example, 50% experience treatment-emergent sexual problems with arousal, erectile dysfunction and orgasm.14 Emotional numbing, cognitive and memory impairment, and sleep disturbance are also common.15 Evidence of analogous effects in healthy volunteers taking antidepressants indicates that such adverse effects do not arise from a mental illness alone.16,17

Other harms are not clinically obvious. Antidepressant RCTs are typically small, brief, and enrol relatively healthy participants; longer-term harms in the real world are detectable only from pharmacoepidemiologic studies. While epidemiological associations must account for confounding factors and do not prove causation,18 antidepressants (including SSRIs and venlafaxine) have been found to increase falls, fractures, osteoporosis, bleeding risk, strokes, dementia, cardiovascular disease, weight gain, cataracts and premature mortality, especially in older people.19-23 An increased risk of withdrawal after long-term use may be another unanticipated harm.24

Is there an optimal way to deprescribe?

Few RCTs have studied how best to stop antidepressants, mostly in people treated for recurrent depression by specialists (total N=4,995 people).25 At least 2 deprescribing trials are now underway in Australia.26,27 Several cohort studies have compared traditional linear tapers and gradual hyperbolic tapers.28

Current recommendations, guidelines, and algorithms are based on the clinical experiences of clinicians and patients – not experimental results. Just as people differ in their tolerance for drugs and dose increases, their experiences of dose reductions vary. This is similar to other drugs that induce pharmacological tolerance and dependence (e.g. nicotine, alcohol, benzodiazepines, and opioids). After antidepressant treatment for more than a few weeks or months, many patients may require a relatively cautious approach to deprescribing.

Speed of tapering

Unsurprisingly, the more slowly antidepressants are stopped, the lower the risk of withdrawal effects or apparent relapse of depression.29 A meta-regression analysis of antidepressant discontinuation RCTs found no increase in depression relapse when doses were tapered over 6 months compared with continuing drug treatment.30 But fast tapering over 1 or 2 months was associated with significantly increased relapse in the largest RCT of deprescribing.31 The meta-regression authors emphasize that antidepressant withdrawal can easily be mistaken for relapse of depression.30

Tapering pattern

The pattern of tapering is also thought to be important. The relationship between the dose and blood concentration of a drug and its effects on receptors in the brain is believed to be hyperbolic. Drug effects rise steeply at doses near the lower end of the approved dose range. But at higher doses and concentrations, many drug effects plateau.29 Hyperbolic dose tapering attempts to mimic this relationship inversely. As the daily dose declines, reductions become progressively smaller. This can be approximated by reducing at an arbitrary percentage, such as 10% per month of the most recent daily dose.

Pragmatic alternatives recommended by many guidelines include stepwise dose reductions over a few weeks, a “slow slide,” or substitution of the very long-lived SSRI fluoxetine for related antidepressants.32 However, even the long elimination half-life of the active metabolite norfluoxetine (mean 9 days, range 4-16 days)33 does not avoid withdrawal in about half of people who take fluoxetine – in whom withdrawal may be delayed for 4-6 weeks after stopping.34

Some people need a very gentle approach. In the United Kingdom (U.K.), a cluster RCT of general practices found that traditional stepwise tapering (e.g. sertraline 200 mg/day, 150 mg/day, 100 mg/day, 50 mg/day, 25 mg/day, stop) was unsuccessful for 58% of patients who had taken at least 9 months of antidepressant therapy for depression or anxiety (N=274 assessable at 6 months).35 For people unable to stop antidepressants in a traditional taper, Dutch researchers have reported success with a much more gradual hyperbolic taper, facilitated with specialized dose “tapering strips.” For example, 608 people mostly taking venlafaxine and paroxetine used 28-day tapering strips to reduce drug doses hyperbolically over schedules of 4 to 20 weeks.28

To reduce withdrawal symptoms markedly, a cautious approach to tapering antidepressants (including hyperbolic dose reductions) is now recommended by the UK National Institute for Health and Care Excellence (NICE) and a number of UK specialty organizations.36,37

Safe and effective deprescribing in practice

The rate and pattern of tapering are clinical decisions specific to the circumstances and needs of individual patients. The Canadian Medication Appropriateness and Deprescribing Network provides a convenient, concise, and lucid guide for patients, their family or friends, and clinicians (also available in French).32

As a general rule, people who have taken an antidepressant for more than 4 weeks should preferably not stop abruptly. A practical approach to avoid or minimize withdrawal is a test dose reduction, using the patient’s response to determine further steps. Barring an urgent need to stop the antidepressant, slow decrements are reasonable. One can accelerate the pace as tolerated. A very slow taper implies a few weeks or months of unnecessary drug exposure. On the other hand, excessively rapid dose reduction potentially risks akathisia, suicide, or possible years of disability. Poor outcomes are not always reversible.1

Patients can be risk stratified based on duration of use, type of antidepressant, past experience of stopping and dose.38,39 People who have taken an antidepressant for only several weeks are at low risk of serious withdrawal, compared with those with years of exposure. Past experience of withdrawal, and high doses, also predict future risk. But the smallest doses used clinically affect amine transporters and brain receptors almost as much as maximum doses. Therefore, even a “low” dose of an antidepressant often confers a substantial risk of withdrawal upon discontinuation.

Without direct comparisons between antidepressants after long-term use, withdrawal risk categories are inherently arbitrary. Table 1, adapted from a review of data available in 2022,34 shows categorical risk estimates for frequent or severe withdrawal, and published incidence estimates for antidepressants commonly used in Canada.

Table 1: Comparative risks for withdrawal after stopping antidepressants

Two analyses of the World Health Organization’s adverse drug reaction (ADR) database also identified paroxetine, venlafaxine/desvenlafaxine, duloxetine, sertraline, and citalopram/escitalopram as the highest risk for withdrawal.40,41 However, this could reflect ADR reporting biases for newer antidepressants. A 2023 Canadian guideline on treatment of depression provides different ratings, but does not cite sources.42 And a 2024 systematic review of short RCTs and observational studies also identified imipramine (the original tricyclic antidepressant) as especially problematic.43

Starting an antidepressant taper

For low-risk patients (weeks of use, low risk antidepressant), a rule of thumb is to start with a 25% dose reduction. For patients deemed at moderate risk (months of use, moderate risk antidepressant), reducing by 10% may be more appropriate. For patients expected to be at high risk for withdrawal (years of use, high risk antidepressant, significant prior problems with withdrawal), a 5% initial reduction is unlikely to cause serious problems.

After starting a dose taper, experts in deprescribing antidepressants recommend monitoring patients clinically for 2-4 weeks per step, to assess the response. In “slow slide” or “hyperbolic” tapering, milligram reductions in daily dose become smaller and smaller as the dose declines. Table 2 shows a hyperbolic tapering schedule that would last well over 1 year for the Vignette patient who took venlafaxine 75 mg/day for 19 years.1

Table 2: Hyperbolic dose tapering: example of venlafaxine 75 mg/day

Schedules recommended by the Canadian Medication Appropriateness and Deprescribing Network are somewhat faster.32 The ongoing Australian RELEASE deprescribing RCT also provides a series of possible “slow” and “slower” schedules for 15 antidepressants.44

Expert advice –  in the absence of evidence from trials

English and Dutch physicians with substantial deprescribing experience indicate that people at low risk can generally stop in 6-9 months, and people at moderate risk in 9-18 months. But high-risk patients may require 2 years or longer. Other experienced clinicians indicate that people treated only briefly with an antidepressant may be able to stop within 2-4 weeks without problematic withdrawal.32 As with other habituating drugs like nicotine, alcohol, and caffeine, some patients may simply prefer to stop “cold turkey,” after short-term use of antidepressants.

Difficult withdrawal symptoms often improve by pausing dose reductions, or retreating a step or two in dose reduction, and slowing the taper. Profound suffering can necessitate reinstating the original dose. Prescribing other drugs to suppress withdrawal substitutes another potential problem, so it is clinically more sensible to interpret withdrawal symptoms as a useful signal to slow the tapering process.

Practical aspects for clinical practice

  1. Explain the process: inform patients about risks of tapering too rapidly, and that gradual tapering appears to minimize withdrawal problems. Balance the rate of taper against harms of long-term antidepressant use, and adjust to the experience of individual patients.
  2. Facilitate tapering with appropriate drug formulations, when necessary: available tablets and capsules are not suited to very slow tapering. Even fragments of the lowest dose tablets or part of a capsule produce high neuronal receptor occupancy and end organ effects. Hyperbolic tapering requires provision of much smaller doses. In Canada, fluoxetine oral solution is one option – including for “cross-tapering” from another antidepressant.45 It is covered by Pharmacare in BC. But, it too should be tapered carefully.
    Compounding pharmacies can produce small doses as liquids, capsules or tablets, equivalent to the tapering strips popular in the Netherlands.28 This service is not covered by Pharmacare, and could be expensive. Some patients use techniques devised by pharmacists to overcome swallowing difficulties.46,47 This can include subdividing tablets with a pill splitter, crushing tablets, using the powdered contents of capsules to make suspensions, opening capsules to count or weigh beads, or even weighing tablet fragments.1 Pharmacists can provide guidance on technical issues such as tablet splitting.
  3. Alternate day dosing often not appropriate: Because the elimination half-life of many antidepressants is <1 day, every-second-day dosing can produce wide fluctuations in drug concentrations, and precipitate severe withdrawal effects.48 If inter-dose withdrawal symptoms arise, divided daily doses can be helpful. Fluoxetine is an exception, because both the parent drug and its active metabolite have very long half-lives.33
  4. Evidence for switching to fluoxetine is equivocal: Although its long elimination half-life and availability as a liquid formulation are obvious advantages for tapering, fluoxetine is not a panacea. Withdrawal is not unusual, even if it is often misdiagnosed because of delayed onset.34,41 Diverse antidepressant effects on neurotransmission and other brain processes may not be replaced adequately by a substitute drug.1 This differs from the typical interchangeability of benzodiazepines, opioids, or beta-blockers. Tapering the antidepressant already familiar to the patient can simplify clinical assessments.
  5. Managing withdrawal-induced akathisia: Reinstating or increasing the dose of the antidepressant may improve symptoms, especially soon after symptom onset.1,49 Akathisia normally resolves spontaneously; but when symptoms persist for months or longer, they can be unbearable. Using other drugs to suppress akathisia yields mixed results; patients can be exquisitely sensitive to psychotropic drugs, sometimes with negative responses.1 If a short trial of another drug is ineffective, continuing it is irrational.
  6. Managing protracted withdrawal: Although this affects only a small minority of patients, it can be very difficult to treat if it occurs. The term “protracted withdrawal” is misleading because it implies that resuming the drug will resolve the syndrome, which is not always the case.1,48,49 A conservative approach is to wait for improvement to occur – generally over months or even years. Non-pharmacological techniques to manage ongoing psychological symptoms are sometimes helpful.Resuming the withdrawn drug at a low dose, months after stopping it, can have unpredictable effects, including paradoxical worsening of symptoms.1,48,50 To mitigate these risks, clinicians experienced with antidepressant deprescribing recommend a very small test dose (e.g. 2 mg of venlafaxine, or 1 mg of citalopram), with further steps determined by the patient’s response.1 This helps determine whether to increase the tiny dose cautiously, or to abandon the approach. As with treating withdrawal-induced akathisia, prescribing other psychotropic drugs as sedatives or to numb symptoms, should be a last resort.1,42,43 The U.K. government has called for specialist services to help manage such patients.51,52 In British Columbia, Primary Care Network (PCN) pharmacists may be able to assist.

Vignette resolution: Your new patient has taken venlafaxine 75 mg/day for 19 years. Given her prior experience trying to reduce the dose to 37.5 mg/day, she is at high risk for a withdrawal syndrome if she stops precipitately. But you agree that stopping venlafaxine is reasonable, and propose a cautious approach. After thorough discussion, you provide her with written information,32 and plan to request preparation of progressively smaller doses by a compounding pharmacist. You inform the patient that she may have to pay for this service. At the next visit, you and your patient can agree on a supervised taper and a first follow-up in 2 weeks.

Multiple experts and primary care clinicians reviewed the draft of this Therapeutics Letter for factual accuracy, and to ensure it is relevant to clinicians.
The UBC TI is funded by the BC Ministry of Health to provide evidence-based information about drug therapy. We neither formulate nor adjudicate provincial drug policies.
ISSN: 2369-8691
International Society of Drug Bulletin LogoThe Therapeutics Letter is a member of the International Society of Drug Bulletins (ISDB), a world-wide network of independent drug bulletins that aims to promote international exchange of quality information on drugs and therapeutics.

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