Stopping Antidepressants – The Antidepressant Discontinuation Syndrome
Discontinuation symptoms may occur after stopping many drugs including antidepressants. ‘Discontinuation syndrome’ is the preferred term since ‘withdrawal syndrome’ implies addiction. Symptoms can often be explained in terms of receptor rebound – e.g. an antidepressant with potent anticholinergic side effects may cause diarrhoea, headache, nausea, vomiting, and restlessness on discontinuation. Discontinuation symptoms may be entirely new or similar to the original presentation of illness, and are experienced by a third or more of patients.
Onset is usually within 5 days (generally 24-72 hours) of stopping the antidepressant, occasionally whilst tapering a dose or even after a single missed dose of short half-life antidepressants such as paroxetine or venlafaxine. Usually these effects are mild and self-limiting, lasting for 7-14 days, but can sometimes be prolonged and quite severe.
Why is it important clinically?
If the discontinuation symptoms are mistaken for relapse or a new physical illness may result in interference with daily functioning, unnecessary tests or treatments. Patients may misinterpret the symptoms to mean they are addicted to antidepressants and may then not want further treatment.
Who is most at risk?
Antidepressants with a short half-life are most likely to produce discontinuation symptoms (e.g. paroxetine and venlafaxine) – irregular dosing can increase this risk (two-thirds of patients may skip odd doses). Those people who developed marked anxiety symptoms at the start of treatment, who take other centrally acting drugs (e.g. antihypertensives, antihistamines, antipsychotics), children and adolescents and those who have had such discontinuation symptoms before are more at risk of discontinuation symptoms, especially after 8 weeks or more of treatment
How to avoid discontinuation syndrome?
Antidepressants should ideally be discontinued slowly, over at least 4 weeks, with gradual dose reduction (except fluoxetine). This is more important the higher the risk of such symptoms is (see above). Patients receiving MAOIs may need even longer. Anyone at risk should be tapered more slowly.
The UK Drug and Therapeutics Bulletin (1999) recommends:
- After less than 8 weeks treatment, withdraw over 1-2 weeks.
- After 6-8 months treatment, taper over 6-8 weeks
- After long-term maintenance treatment, reduce the dose by 25% every 4-6 weeks.
If symptoms occur despite a slow dose reduction it might be better to discuss a more rapid withdrawal with the patient. It may be more preferable to them to suffer more severe symptoms for a shorter duration than milder but longer lasting symptoms?
The perception of symptom severity is probably made worse by the absence of forewarning and it is important to educate patients so that they know about the possibility of discontinuation symptoms and what to expect.
Any treatment of discontinuation syndrome is not based on clinical trials, but anecdotal evidence. For milder symptoms patients may require reassurance that they are not relapsing or becoming physically ill and education may be enough. More severe symptoms may require reintroduction of the original antidepressant until symptoms resolve and then smaller dose reductions over a longer period of time.
Discontinuation symptoms by antidepressant group:
|Drugs most commonly associated with discontinuation
|Agitation, irritability, ataxia, movement disorders, insomnia, somnolence, vivid dreams, cognitive impairment, slowed speech, pressured speech.
|Hallucinations, paranoid delusions.
|Tranylcypromine is partly
metabolised to amphetamine and is therefore associated with a true ’withdrawal syndrome’.
|Flu-like symptoms, cholinergic rebound (headache, restlessness, diarrhoea, nausea and vomiting), sleep disturbance (insomnia, dreaming), lethargy.
|Movement disorders, mania, cardiac arrhythmias.
|Flu-like symptoms, electricshock
like sensations in the head, abdominal cramps, dizziness, vertigo, insomnia, vivid increased dreaming, agitation and irritability, crying spells, fatigue, sensory disturbance.
|Movement disorders, poor concentration and memory.
|Paroxetine and venlafaxine
[Fluoxetine least likely]
Key points to inform patients:
- Antidepressants are not addictive.
- Discontinuation symptoms may occur when antidepressants are discontinued.
- The most likely symptoms associated with the drug that he/she is taking.
- Antidepressants (except fluoxetine) should not be stopped abruptly, but the dose should be gradually tapered over at least 4 weeks. Follow instructions given by Doctor.
- Discontinuation symptoms usually start within 1-2 days of stopping an antidepressant and generally resolve within 2 weeks.
- Discontinuation symptoms may occur after missed doses if the antidepressant has a short half-life e.g. venlafaxine, paroxetine.
- Taylor D, Paton C, Kerwin R. The South London and Maudsley NHS Trust, Oxleas NHS Trust
2005-2006 Prescribing Guidelines, 8th Edition. Martin Dunitz.
- Drug and Therapeutics Bulletin 1999; 37: 49-52.
- Bazire S. Psychotropic Drug Directory 2005. Fivepin Limited.
Prepared by: Wendy Ackroyd BSc, MRPharmS, February 2004
Revised: September 2005
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