Considerations for reduction and/or stopping an antidepressant

Note: Nine months was assessed as being an appropriate point when an individual may have completed a six-month course of treatment for first episode of depression and account for the time required to receive an effective antidepressant and dose. For example, first antidepressant partially effective at four weeks, then required to switch to alternative antidepressant, dose titration where appropriate, then six-month course for people achieving remission.

The strategy for reducing/stopping antidepressants should be guided and informed by the individual’s preferences and needs. Consider the clinical situation when reviewing and discussing reducing/stopping antidepressants. Encourage individuals to discuss stopping their antidepressants with their prescriber before doing so.

By discussing and planning withdrawals, the most appropriate rate of reduction can be agreed and planned with the individual, according to their preferences and needs:

If experiencing serious adverse effects/harms - may require rapid discontinuation within seven days or less (see the table below).
Completed a nine month or less course of antidepressant treatment e.g. with first episode of moderate to severe depression – reduce over a minimum of four weeks. Some individuals may need a slower reduction e.g. four weekly stepped reductions. (Shorter courses of antidepressant treatment may be less likely to be associated with discontinuation/withdrawal effects. However, the rate of reduction should be guided by the individual’s preferences and needs.)
Completed a longer course (nine months or more) of antidepressant treatment, and/or a history of recurrent depression or anxiety. Reducing and tapering the dose at a slower rate over months may be more appropriate, e.g. for people with anxiety disorders who have responded to antidepressants and received long-term treatment a minimum of three months or longer, tapered reduction is recommended.
Anxious about reducing/withdrawing antidepressants or history of experiencing discontinuation effects. Reducing and tapering the dose at a slower rate over months may be more appropriate.

Where people experience significant or unbearable withdrawal effects during reduction, increasing back to the previous dose that did not cause withdrawal symptoms, and after stabilising, considering a slower rate of reduction may help.

Serious adverse effects/harms which may require rapid discontinuation

Adverse effect

Drugs

Symptoms/signs

Serotonin syndrome (very rarely occurs)

SSRI, SNRI, clomipramine, moclobemide, other medicines e.g. triptans, tramadol, fentanyl, etc.

Mild (individual may/may not be concerned): insomnia, anxiety, nausea, diarrhoea, hypertension, tachycardia, hyperreflexia

Moderate (causes distress): agitation, myoclonus, tremor, mydriasis, flushing, diaphoresis, low fever (<38.5°C)

Severe (medical emergency): severe hyperthermia, confusion, rigidity, respiratory, coma, death

QTc interval prolongation

Citalopram, escitalopram, TCAs, and other medicines e.g. quinine, methadone, antipsychotics, antibiotics etc.

ECG changes in QTc interval

Note: Serotonin syndrome, for more detail see Buckley et al. 2014¹³⁸ and Isbister 2007 QTc prolongation is of concern as it is associated with ventricular tachycardia and sudden cardiac death, see Kallergis et al. 2012.⁵¹

Assess the individual’s readiness to reduce and/or stop

It is important that an individual’s motivation and readiness for reduction and/or discontinuation is adequately assessed. Where agreed a tailored dose reduction should be planned, and where implemented, regularly reviewed. Signposting or referral for interventions to support changes to prescribing should also be considered, including psychosocial or psychological interventions.

What is the risk-benefit balance of continuing current antidepressant dose?

Example considerations may be:

balancing anticholinergic effects versus neuropathic pain control
reducing the signs and symptoms of the condition it was prescribed for

or the

need to stop the antidepressant due to increased risks e.g. cardiovascular disease, QTc prolongation risk or a newly diagnosed condition

Has the individual completed the planned and agreed course or trial of treatment?

For example, in relation to depression, is the individual experiencing residual symptoms such as sleep issues, irritability and ruminating, motivation (have they managed to do something they like to do) and do they have plans for the future (moving on from depressive episode)?

These factors may indicate that an individual is suitable to consider reducing and stopping their antidepressant after completing an appropriate course of treatment. This can be six months for the first episode of depression or 12 or 24 months of treatment, depending on the number of depressive episodes and relapses.

Discontinuation/withdrawal symptoms

These may begin on average within two days (up to five days) after stopping and occasionally following dose reduction or missed doses. Generally, these symptoms subside within seven to ten days,^18,20 but may include a wide range of symptoms which can vary in intensity, depending on which antidepressant is being stopped (see the two tables below). For some people these symptoms are mild and self-limiting, however, others may experience severe or prolonged discontinuation or withdrawal symptoms e.g. flu-like symptoms, electric shocks (brain zaps), vivid dreams, dizziness or diarrhoea. Unfortunately, the optimum rate of taper to prevent discontinuation/withdrawal symptoms is unknown.^22,23

Clinical presentation of discontinuation/withdrawal symptoms

	Symptoms
Systemic, cardiac effects	Flu-like symptoms, dizziness/drowsiness*, tachycardia (fast heart rate), impaired balance, fatigue, weakness, headache, dyspnoea (breathlessness)
Sensory	Paraesthesia (burning, prickling sensation), electric shock–like sensation (“brain zaps/body zaps”), sensory disorders, dysesthesia (abnormal unpleasant sensation e.g. burning, itching), itch, tinnitus, altered taste, blurred vision, visual changes
Neuromuscular	Muscle tension, myalgia (muscle pain), neuralgia (nerve pain), agitation, ataxia (lack of muscle co-ordination)*, tremor, akathisia (inner restlessness, urgent need to constantly move, inability to stand/sit still)
Vasomotor	Perspiration, flushing, chills*, impaired temperature regulation
Gastrointestinal	Diarrhoea, abdominal pain, anorexia, nausea, vomiting
Sexual	Premature ejaculation, genital hypersensitivity
Sleep	Insomnia, nightmares, vivid dreams, hypersomnia (excessive sleepiness)
Cognitive	Confusion, disorientation, amnesia*, reduced concentration
Affective	Irritability, anxiety, agitation, tension, panic, depressive mood, impulsivity, sudden crying, outbursts of anger, mania, increased drive, mood swings, increased suicidal thoughts, derealization, depersonalization
Psychotic	Visual and auditory hallucinations
Delirium	Typically only with tranylcypromine

Adapted from Henssler et al 2019¹³⁰ and Haddad et al.¹⁴⁰ Symptoms in bold occur more frequently.

*Serotonin related

Antidepressant discontinuation/withdrawal symptoms

Antidepressant class	Most commonly associated^a	Common symptoms^b	Occasional symptoms^b
SSRI, Clomipramine (TCA)	Paroxetine	Flu-like symptoms (chills, myalgia, excess sweating, nausea, headache), ‘shock-like’ sensations, dizziness exacerbated by movement, insomnia, excess (vivid) dreaming, irritability, crying spells	Movement disorders, concentration, memory difficulties
SNRIs	Venlafaxine	Same as above, due to serotonin effects	Same as above
TCAs	Amitriptyline Imipramine	Flu-like symptoms, insomnia, excess dreaming Anticholinergic rebound – more common in older adults: headache, restlessness, diarrhoea, nausea and vomiting	Movement disorders, mania, cardiac arrhythmias
Other	Mirtazapine^c	Anxiety, panic attacks, insomnia, irritability, nausea	-
Other	Agomelatine	-	No discontinuation symptoms have been reported^d
Other	Trazodone	-	Rarely SSRI type withdrawals^e
Other	Vortioxetine	-	No discontinuation symptoms have been reported^f

Although most commonly associated with the listed medicines, other medicines in the group may cause similar symptoms.
Symptoms: As individuals may or may not experience discontinuation/withdrawal symptoms, and the intensity and range of symptoms may vary by individual, people may experience or identify symptoms not listed above.
Limited data: mirtazapine case studies, see Cosci et al. 2017.¹⁴¹
At time of writing no case reports in literature. Agomelatine rarely used.
See Haddad et al. 2001¹³⁶ and Otani et al. 1994¹⁴² for more detail.
Adapted from and informed by Maudsley and Psychotropic Drug Directory. Vortioxetine rarely used.