Deprescribing Antidepressants: When To Consider It And How To Do It

Figure 1 – International Antidepressant Consumption Over Time [OECD, 2025]

An increase in antidepressant prescribing alone is not evidence of inappropriate prescribing. [Looi et al., 2025]

That said, there is a growing recognition that antidepressant deprescribing should more readily be considered in patients who are clinically stable.

The decision to cease antidepressant therapy is made challenging by differing clinical guidelines, fears about recurrence of depression & risk of suicide, and limited clinical experience with antidepressant discontinuation.

The RANZCP Clinical Practice Guidelines for Mood Disorders suggest that for major depressive disorder, patients should stop their antidepressant medication after they have been in remission for 9 months to a year. [Malhi et al., 2021]

The Clinical Practice Guidelines for the Treatment of Panic Disorder, Social Anxiety Disorder and Generalised Anxiety Disorder recognise limited evidence available in regard to the optimum duration and suggest continuation until avoidance behaviours have been overcome and remission of symptoms rather than a specific time period. [Andrews et al., 2018]

In both guidelines, tapering on cessation is recommended without any specificity, the former suggesting an “extended period” and the latter advising a period of “weeks to months”.

Concerns have been raised that limited guidance to do this means it is not prioritised, and patients may not be aware they have the choice to do this. [Ranwala et al., 2025]

This has become an important issue for anyone who prescribes these medications, given that the issue has entered the mainstream media and consumers of mental health services are encouraged to be active participants in their care more than ever.

Proportional tapering of antidepressants has traditionally been the method for cessation, generally involving dose reductions of a fixed percentage (i.e. 50%) until at a low enough dose to cease (generally half the lowest unit dose).

In recent years, hyperbolic tapering has been recognised as an important alternative method, particularly for those unable to cease antidepressants via proportional tapering.

Hyperbolic tapering involves a stepwise, non-linear dose reduction, primarily based on receptor occupancy rather than on specific dose, with initial reductions being the greatest and later reductions becoming increasingly small and as prolonged as is required for each individual patient. This method forms the basis of the recently released Maudsley Deprescribing Guidelines. [Horowitz & Taylor, 2024]

The RANZCP has featured the authors of these guidelines via a webinar, and the RACGP has endorsed the guidelines, which is relevant given that in 2023-24, 92% of antidepressant prescriptions were provided by GPs, whilst psychiatrists (5%) and other specialists (3%) provided the remainder.[Australian Institute of Health and Welfare, 2025]

It is also important to recognise the limitations of hyperbolic tapering, which may be logistically onerous for patients and practitioners and often requires collaboration between prescriber and pharmacist.

A key difference between the UK, where the Maudsley Guidelines were composed, and Australia is the availability of liquid preparations, often recommended for ease of dosing in the later stages of a taper.

Australian consumers have access to escitalopram as an oral liquid, whilst fluoxetine is available as a dispersible tablet. Comparatively, in the UK, eight of the top ten most commonly used ADs are available in liquid or dispersible form, whereas in the USA this figure is six out of ten. [Horowitz & Taylor, 2024]

A recent meta-analysis on the incidence of antidepressant withdrawal symptoms in individuals using antidepressants for a short period of time found that while those who discontinued an antidepressant reported one more symptom of discontinuation compared to those who ceased a placebo or continued on an antidepressant, the most common of which was dizziness. [Kalfas et al., 2024]

It is also necessary to consider the duration of taper: one cohort study found that withdrawal symptoms are most pronounced in those undergoing a 28-day taper, suggesting that a longer tapering trajectory may reduce their incidence. [van Os & Groot, 2023]

THE HOW OF DEPRESCRIBING – WORKED EXAMPLES:

The initial approach to antidepressant de-prescribing should be reducing the dose by 50% every 2-4 weeks until the medication is at its lowest available dose and then ceasing it 2-4 weeks later. This approach will work for most patients. [Lewis et al., 2021]

However, for patients who experience significant discontinuation symptoms, a hyperbolic tapering approach will be required. The worked examples below show suggested dose reductions and the resulting estimated receptor occupancy (RO).

These steps are to take place every 2-4 weeks, but not less than 1 week, depending on patient preference and tolerability.

They have been adapted from the Maudsley Deprescribing Guidelines for the Australian setting, taking into account key differences in the availability of specific formulations.

Where dilutions, solutions or suspensions are required, it should be noted that these need to be used immediately and discarded. Examples include selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), mirtazapine and tricyclic antidepressants (TCAs). [Horowitz & Taylor, 2024]

Table 1 represents a hyperbolic taper of escitalopram, the only SSRI available in Australia as a liquid, as noted above. Receptor refers to the serotonin transporter (SERT). The starting dose of 20mg would achieve Receptor Occupancy (RO) of 79%. Further guidance on SSRI tapering is available here.

Table 1 – Hyperbolic tapering of Escitalopram

Table 2 shows that a hyperbolic taper of venlafaxine, an SNRI, is commonly implicated in withdrawal syndromes both in terms of incidence and severity (15). Similar to escitalopram the receptor refers to serotonin transporter (SERT). The starting dose of 300mg would achieve an RO of 88%. [Horowitz & Taylor, 2024]

Table 2 – Hyperbolic tapering of Venlafaxin [Horowitz & Taylor, 2024]

Table 3 shows that mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), has receptor activity at serotonergic, adrenergic and histaminergic receptors, and in this case, receptor occupancy refers to the alpha 2 adrenoreceptor. The starting dose of 45mg would achieve an RO of 32.8%. [Horowitz & Taylor, 2024]

Table 3 – Hyperbolic tapering of Mirtazapine [Horowitz & Taylor, 2024]

Finally, amitriptyline, a common TCA, interacts with a vast array of receptors, including serotonergic, adrenergic, histaminergic and muscarinic receptors, all of which are thought to be hyperbolic relationships. Receptor occupancy is unable to be estimated, given that no neuroimaging has been undertaken to quantify amitriptyline’s receptor occupancy. Other TCAs, meanwhile, do have receptor occupancy data available, with the norepinephrine transporter (NET) being the identified receptor for clomipramine and nortriptyline, while dosulepin is measured based on its histamine (H1) receptor occupancy. [Horowitz & Taylor, 2024]

Table 4 – Hyperbolic tapering of Amitriptyline [Horowitz & Taylor, 2024]

A key part of the deprescribing process is the ongoing monitoring, particularly for both relapse and withdrawal syndromes.

This presents a challenge, given that relapse and withdrawal can present similarly, as demonstrated by the significant overlap of available rating scales, the Hamilton Depression Rating Scale (HAM-D) and Discontinuation-Emergent Signs and Symptoms (DESS) checklist.

Symptoms such as low mood, anxiety, sleep disturbances, cognitive disturbance, and physical disturbances (GI upset, headaches) are common to both. Differentiating the cause requires a good history with specific timelines as well as screening for items specific to the DESS, including “electric shock” sensations, vivid nightmares, and vertigo.

Relapse prevention is also cited as a reason for continuation of antidepressants, though a randomised double-blind trial of adults in general practice who had been taking antidepressants for 2 years or longer found antidepressant cessation led to a higher relapse of depressive episodes in 56%, compared to 39% of those who continued on their maintenance dose. [Lewis et al., 2021]

This indicates a higher risk of relapse, but also that a significant portion of those who discontinued antidepressants did so without relapse (and long-term antidepressants will not necessarily prevent relapse in those who continue).

This study, which did not involve hyperbolic tapering, also shows that most patients can have their antidepressants withdrawn successfully without the use of hyperbolic tapering. Hyperbolic tapering should be reserved for those in whom this approach is unsuccessful.

Clinical suspicion of a withdrawal syndrome may also be dependent on the antidepressant itself, with factors such as shorter half-life, higher dose and longer duration of treatment all contributing to a higher risk of withdrawal. [Quilichini et al., 2022]

To explore the antidepressant withdrawal diagnosis and management further, please refer here.

Antidepressants continue to be used at high levels in Australia and other OECD countries. At the same time, there are growing concerns that a proportion of antidepressant use may be inappropriate or prolonged beyond the period of clear benefit.

Where deprescribing is clinically indicated, patients should be fully informed of the different means of achieving this, though to insist on hyperbolic tapering for all would be resource-intensive and impractical. This may actually lead to people remaining on antidepressants for longer than is necessary.

Despite this, hyperbolic tapering offers an approach to reduce withdrawal symptoms and support successful discontinuation, particularly for patients who experience significant antidepressant discontinuation syndromes or who have had difficulty tapering using linear dose reductions and should be core knowledge for anyone prescribing or deprescribing these medications.

Ultimately, the choice to taper via traditional or hyperbolic means will be a joint decision between doctor and patient. We recommend that a simple tapering approach – reducing the dose by 50% every 2-4 weeks – is the optimal first approach. Hyperbolic tapering should be reserved for those who do not tolerate standard tapering measures.

1. What is antidepressant deprescribing?

Antidepressant deprescribing refers to the planned, supervised reduction and cessation of antidepressant medication when ongoing treatment is no longer clearly indicated or when the risks, adverse effects, or burden of treatment outweigh expected benefit. It should involve clinical review, patient discussion, tapering, and monitoring for relapse or withdrawal symptoms.

2. When should antidepressant deprescribing be considered?

It may be considered when a patient is clinically stable, has remained in remission for an appropriate period, experienced only mild or minimal depressive symptoms at the time of prescribing, or wishes to review the need for long-term medication. The decision should be individualised, particularly in patients with recurrent depression, severe prior episodes, suicidality, comorbid anxiety disorders, or previous difficulty stopping medication.

3. What is the difference between proportional and hyperbolic tapering?

Proportional tapering usually involves reducing the antidepressant dose by a fixed proportion, such as 50%, every few weeks until the lowest available dose is reached. Hyperbolic tapering uses progressively smaller dose reductions at lower doses, reflecting the non-linear relationship between dose and receptor occupancy. It is particularly relevant for patients who develop significant discontinuation symptoms during standard tapering.

4. Is hyperbolic tapering needed for all patients stopping antidepressants?

No. The article recommends a simple tapering approach as the initial strategy for most patients, with hyperbolic tapering reserved for those who do not tolerate standard tapering or who experience clinically significant withdrawal symptoms. Using hyperbolic tapering for every patient may be impractical and could unnecessarily prolong antidepressant use.

5. How can clinicians distinguish antidepressant withdrawal from relapse?

Withdrawal and relapse may share symptoms such as low mood, anxiety, sleep disturbance, cognitive symptoms, gastrointestinal upset, and headaches. A careful timeline is essential. Features more suggestive of withdrawal include symptoms emerging soon after dose reduction or cessation, as well as discontinuation-specific symptoms such as “electric shock” sensations, vivid nightmares, and vertigo.

6. Which antidepressants are more associated with withdrawal symptoms?

Withdrawal risk may be higher with antidepressants that have a shorter half-life, higher doses, longer treatment duration, or a previous history of discontinuation symptoms. Venlafaxine is highlighted as an antidepressant commonly associated with withdrawal syndromes.

7. Does stopping antidepressants always lead to relapse?

No. While antidepressant cessation can increase relapse risk, many patients discontinue successfully without relapse. This reinforces the need for careful patient selection, shared decision-making, and monitoring rather than assuming indefinite treatment is always required.

8. What monitoring is needed during antidepressant deprescribing?

Monitoring should include withdrawal symptoms, depressive relapse, anxiety, sleep disturbance, suicidality, cognitive symptoms, physical symptoms, and functional deterioration. A clear timeline of dose changes and symptom emergence is essential.

9. What is the key clinical message for prescribers?

The key message is that antidepressant deprescribing should be treated as an active clinical intervention. A simple taper is suitable for many patients, while hyperbolic tapering is an important option for those who struggle with standard reductions.