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MHRA guidance (2014): Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs): use and safety
There is a risk of suicidal behaviour with the use of any SSRI and SNRI, particularly when used by children, adolescents or young adults. Refer to Treatment of unipolar depression, for further guidance.
In 2008, a meta-analysis of data on antidepressants, including SSRIs and SNRIs, was completed by the Food and Drug Agency (FDA) in the USA. The results of this analysis were reviewed in both the UK and in Europe.
The UK/EU review concluded that the risk of suicidal acts and behaviour is increased with the use of SSRIs or SNRIs in young people aged up to 25 years. The risks of sertraline, citalopram, escitalopram, paroxetine, venlafaxine, and mirtazapine outweigh the benefits when used in children and adolescents with depression and should not be used in this patient group.
The risk of suicide is greatest in the early stages of SSRI treatment. This may be due to the fact that SSRIs and SNRIs need to be taken for a few weeks before they are effective in treating depression (which is itself associated with an increased risk of suicidal behaviour).
All SSRIs and SNRIs may be associated with withdrawal reactions on stopping or reducing treatment. Withdrawal reactions are less severe when the dose is gradually decreased or 'tapered off' over several weeks. The most commonly experienced withdrawal reactions are: dizziness, numbness and tingling, gastrointestinal disturbances (particularly nausea and vomiting), headache, sweating, anxiety, sleep disturbances. See "Stopping and switching between antidepressants", here.
SSRIs and SNRIs cross the placenta in pregnant women and have the potential to affect the unborn foetus. Pregnant women should only use SSRIs or SNRIs after discussing any potential risks to their unborn child with their doctor. See "Depression in pregnancy and the postnatal period", here. The UK Teratology Information Service (UKTIS) provides a national service on all aspects of the toxicity of drugs and chemicals in pregnancy (Tel: 0344 892 0909), and provides the 'best use of medicines in pregnancy' (bumps) website for supportive information relating to individual treatments.
SSRIs have been associated with a small increased risk of fractures.
MHRA Drug Safety Update (December 2014)
Citalopram and escitalopram: QT interval prolongation
Citalopram and escitalopram have been found to prolong the QT interval in a dose dependent manner. The maximum daily doses for citalopram and escitalopram are restricted – see individual drug entries.
Citalopram and escitalopram are contraindicated in patients at greatest risk of QT interval prolongation, such as those with:
Patients taking concomitant medications known to increase plasma levels of escitalopram and citalopram may require a dose reduction. Drugs known to increase plasma concentrations of escitalopram and citalopram include some antiretroviral medications, and omeprazole and cimetidine.
The balance of benefits and risks of citalopram and escitalopram should be considered carefully; particularly at higher doses, in patients with pre-existing risk factors for QT interval prolongation, for example:
The MHRA suggest the following monitoring recommendations:
For further details refer to BNF and individual manufacturer Summary of Product Characteristics, and see also Drugs that prolong the QT interval, formulary guidance.
MHRA Drug Safety Update (January 2021): SSRI/SNRI antidepressant medicines: small increased risk of postpartum haemorrhage when used in the month before delivery
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