Guidance

Antidepressants: use and safety

Updated 15 October 2026

For up to date information about these medicines, please consult the relevant Summary of Product Characteristics and Patient Information Leaflet on the MHRA’s products page.

1. Overview

There are currently 29 different medicines classified as antidepressants that fall into several different groups. These groups are:

• selective serotonin reuptake inhibitors (SSRIs),
• serotonin and noradrenaline reuptake inhibitors (SNRIs),
• tricyclic antidepressants,
• monoamine oxidase inhibitor antidepressants (MAOIs)
• and “other” antidepressants .

The names of the individual antidepressants can be found at the bottom of this page^{[footnote 1]}. For prescribing information please see MHRA Products

2. Antidepressants and the risk of suicidal thoughts and behaviour

Regulatory history 

In 2003, an expert working group (EWG) established by the Commission on Human Medicines (CHM) considered the safety of antidepressants, including the risk of suicide and suicidal behaviours. The group reviewed all available data, including original clinical trial data, the scientific literature, postmarketing reports and patient testimony, and concluded that:

• generally, in depressed patients the risk of suicide is greatest around the time of their presentation to medical services, however the risk of suicide may increase in the early stages of treatment for depressive illness
• a modest increase in the risk of suicidal thoughts and self-harm for SSRIs compared with placebo cannot be ruled out
• there is insufficient evidence of any marked difference in risk of suicidal thoughts and behaviours  between the different SSRIs, or between SSRIs and other antidepressants

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 of the totality of evidence 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).

There are no marked differences in suicidal risk between the different classes and types of antidepressant and there is no evidence that the use of SSRIs or SNRIs leads to an increased risk of suicide in the general adult population    in those who take antidepressants compared to those who don’t.

On the basis of the UK and European reviews, in 2008 it was agreed that the warning on the risk of suicidal thoughts and behaviour with antidepressants should be included in the Patient Information Leaflets (PILs) and Summary of Product Characteristics (SmPCs) for all antidepressants, including SSRIs and SNRIs. All subsequently licensed antidepressants were required to include a warning on suicidal thoughts and behaviours.

In 2025, an EWG considered the data gathered from patients and families in relation to concerns raised about the effectiveness of the warnings in the approved patient information leaflets. The EWG met on several occasions and heard directly from patients, their families and patient representative organisations. Based on this evidence, the EWG developed recommendations for updates to the product information, which were considered by the CHM in September 2025. The CHM advised that the proposed updates should be user tested   by a group of patients with a range of mental health conditions to ensure the message was clear and understandable for patients. The Patients Association was therefore commissioned to convene a focus group of patients from a diverse range of backgrounds, and with a range of mental health conditions, to finalise the updates to the patient information leaflets.

In addition to the updated information in patient information leaflets:

• a new boxed warning in the PIL has been introduced to better highlight the risk of suicidal thoughts and behaviours.
• It is the expectation that a new robust and portable patient card is implemented which contains key safety messages and advice on where to get help
• the MHRA is working with healthcare system partners to co-develop a safety (ancillary) leaflet that healthcare professionals can give to patients at their first or next consultation to support discussions and decisions about treatment.
• the MHRA is working with healthcare system partner organisations to help ensure that clinical guidance documents are consistent with the regulatory position wherever possible. Partner organisations include NICE, the BNF, the Royal College of Psychiatrists and Royal College of General Practitioners.

The updated information in the antidepressants’ patient information leaflets will state:

Warning – Thoughts of self- harm and suicidal behaviour

This medicine may be associated with thoughts of self-harm and suicidal behaviour in some people.  

Tell someone you trust, who can help you in an emergency, that you are taking this medicine and ask that they read this leaflet  

Talk to your trusted person, prescriber or go to a hospital straight away, if after starting this medicine, you have new or worse:  

• Feelings of anxiety or irritability
• Feelings of restlessness and agitation
• Extreme increases in activity and difficulty sleeping
• Thoughts of acting on dangerous impulses to harm yourself
• Thoughts about suicide or dying
• Changes in behaviour or mood you, or someone you trust, notices and is worried about  

In some people, thoughts of self-harm and suicidal behaviour may be increased when first starting antidepressants. Antidepressants take time to work; and sometimes side effects occur before you or others notice improvements in your mood.   

Never stop taking an antidepressant suddenly without first talking to a healthcare professional. Stopping an antidepressant medicine suddenly can cause other symptoms related to withdrawal to occur.   

Information from clinical trials has shown the highest risk of thoughts of self harm and suicidal behaviour, is in adults aged less than 25 years who were treated with an antidepressant, but the risk applies to people of all ages treated with these medicines.   

Call NHS 111 who can offer you support, until you can be with someone who can help you in person.

The patient card available in electronic and hard copy states:

Patient Card

• This medicine is an effective treatment but can take time to work.
• You may experience some side effects before your symptoms improve
• Please read the leaflet provided in the box of your medicine for more information

Warning: Thoughts of self-harm and suicidal behaviour

• Do not suddenly stop taking this medicine without talking to a healthcare professional
• Tell someone you trust you are taking this medicine
• Ask your trusted person to read the leaflet
• Contact your trusted person, go to a hospital or call NHS 111, or your local NHS mental health crisis team, if you have new or worse thoughts of harming yourself.

The impact of the patient card and updates to the PIL will be monitored through the manufacturer’s risk management plan framework and via a MHRA study in the Clinical Practices Research Datalink.

Further details on the considerations of the EWG can be found in the public assessment report. 

3. Antidepressants and the risk of “Post SSRI Sexual Dysfunction” (“PSSD”)

In 2019, an EU/UK review of data associated with antidepressant use and sexual dysfunction which continued after stopping treatment was conducted. The review concluded that for certain^{[footnote 2]} antidepressants included in that review, long-lasting sexual dysfunction symptoms have continued despite discontinuation of the SSRIs/SNRI.

The term “PSSD” was not included in the update to the product information for those antidepressants where evidence showed an association with sexual dysfunction.

In 2024, the MHRA sought the advice of the CHM on the concerns raised by a number of patients and patient support organisations that there was a lack of awareness of the risk   of long-lasting sexual dysfunction after stopping antidepressants (“PSSD”).  The CHM advised that this potential risk should be considered by the EWG as part of its review of antidepressant risk minimisation measures.

Patients affected by “PSSD” attended the meeting of the EWG on 01 July 2025 to emphasise what they had submitted in written documentation and shared with the MHRA during meetings.  The symptoms reported by patients were associated with a range of antidepressants, not just SSRIs. In addition to sexual symptoms patients also reported non-sexual symptoms.

There is currently no International Classification of Disease (ICD) code for PSSD. “PSSD” is not currently recognised as a formal diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorders (DSM V), however DSM V does state that “in some cases, SSRI-induced sexual dysfunction may persist after the agent is discontinued.”

Despite the limitations associated with the term “PSSD”, patients provided feedback that the term “PSSD” should be specifically mentioned in antidepressant product information.

The EWG recommended that the patient information leaflets for certain^{[footnote 3]} antidepressants should be updated to reflect clinical practice.

The updates to the PILs for certain antidepressants will therefore state:

Medicines like [medicines name] may cause symptoms of sexual dysfunction. Rarely people can experience more persistent sexual side-effects after they have stopped taking SSRIs. The term ‘post SSRI sexual dysfunction’ (PSSD) has been used by some people to describe these symptoms. For these people, PSSD can have a significant and distressing impact on their lives. Research is needed to understand why this happens and how common it is. It is important that people experiencing ongoing sexual side-effects receive appropriate and timely support. 

Further details can be found on the considerations of the EWG in the public assessment report.

4. SSRIs/SNRIs and the risk of withdrawal reactions

The MHRA Is currently undertaking a review of the communication of withdrawal reactions. The outcome of this review will be communicated on its completion.

5. Safety concerns with SSRI/SNRI use in pregnancy

SSRIs and SNRIs cross the placenta in pregnant women and have the potential to affect the unborn foetus.

5.1 Persistent pulmonary hypertension in newborn infants

Persistent pulmonary hypertension in the newborn (PPHN) is a disorder of the heart and respiratory system in a newborn baby which causes breathing and circulation difficulties, and is associated with an increase in mortality.

The symptoms usually begin during the first 24 hours after birth and include:

• fast breathing
• inability to sleep or feed properly
• a blue-ish tinge to the skin
• vomiting

After a review of data from scientific studies (Chambers and colleagues, 2006; Kallen and Olausson, 2008), the MHRA advised healthcare professionals that:

• SSRI use later in pregnancy, particularly after the twentieth week, may increase the risk of PPHN; the normal background risk of PPHN is 1–2 cases per 1000 pregnancies and this risk increases to approximately 5 cases per 1000 pregnancies with maternal SSRI use
• although there is currently no evidence for an association of PPHN with SNRIs, a potential risk cannot be ruled out as their mechanisms of action are very similar

The SmPC for all SSRIs and SNRIs have been updated with the new information.

5.2 Neonatal serotonergic effects and withdrawal symptoms

Some evidence suggests that exposing an unborn child to SSRIs or SNRIs in the womb is associated with complications when the baby is born, such as neonatal abstinence syndrome (NAS) - a withdrawal syndrome seen in newborn babies. Therefore, the MHRA advises that:

• discontinuation/withdrawal symptoms may occur in newborns if SSRIs or SNRIs are used until or shortly before birth
• pregnant women should only use SSRIs or SNRIs after discussing any potential risks to their unborn child with their doctor.
• female patients should inform their doctor if they become pregnant during treatment with these drugs
• newborn babies should be observed by a health professional if maternal use of an SSRI or SNRI continues into the later stages of pregnancy, particularly the third trimester

Symptoms which may occur in newborn babies after maternal SSRI/SNRI use in later stages of pregnancy include:

• irritability
• tremor
• muscle weakness
• persistent crying
• difficulty in sucking or sleeping.

These symptoms could be due to either serotonergic effects or discontinuation symptoms. In the majority of cases the complications begin immediately or soon (less than 24 hours) after delivery.

5.3 Other safety concerns with SSRI use during pregnancy

Use of SSRIs in the first 3 months of pregnancy and the risk of birth defects

It is estimated that between 7 in 100 and 20 in 100 pregnant women may experience symptoms of depression.   It is important to treat depression in pregnancy, as it is associated with a variety of adverse outcomes for both the unborn baby and the mother. It is also important that the safety of any antidepressant medicines given in pregnancy is adequately monitored.

A regulatory review of available data in 2005  assessed a possible association between exposure to paroxetine (brand name Seroxat) in the first trimester of pregnancy and the risk of congenital malformations (birth defects) in the developing foetus.

The results suggest that there is an increased risk of all malformations, particularly cardiovascular, in infants exposed to paroxetine during the first trimester of pregnancy (less than 2 in 100 pregnancies). The background (naturally occurring) incidence of any congenital malformation is approximately 1 in 100.

A similar meta-analysis on possible congenital defects with SSRI use was conducted for fluoxetine in 2009. The results of this analysis suggest that fluoxetine first trimester use in pregnancy is not associated with a risk of non-cardiac birth defects. However, the results also showed that the use of fluoxetine in the first trimester of pregnancy is associated with a small increased risk (less than 2 in 100 pregnancies) of congenital cardiac defects in the unborn child.

The level of risk is similar to the level of risk associated with maternal paroxetine use. The background (naturally-occurring) incidence of congenital cardiac defects is approximately 1 in 100.

6. Other safety concerns with SSRI use

6.1 SSRI antidepressants and the risk of bone fractures

The MHRA has issued advice to healthcare professionals  and patients about a small increased risk of fractures associated with the use of SSRIs and another group of antidepressant medicines called tricyclic antidepressants (TCAs).

A review of epidemiological studies shows an increased  risk of bone fractures in patients receiving SSRIs and TCAs.

The mechanism leading to this increased risk is unclear and is probably multifactorial. Healthcare professionals should be aware of the potential risk of fractures in patients taking, or starting to take SSRIs or TCAs, to better inform their discussions with patients and the decision-making processes in prescribing these medicines.

6.2 The effects of SSRIs on tamoxifen effectiveness

Some SSRIs may interfere with the cancer-fighting actions of tamoxifen if they are given around the same time.

Tamoxifen is a medicine used to treat oestrogen-receptor-positive breast cancer in premenopausal and postmenopausal women. Tamoxifen is a prodrug and the formation of its active metabolite endoxifen is mediated by the cytochrome P450 isoenzyme 2D6 (CYP2D6).

Some medicines such as SSRIs (which are commonly prescribed to treat depression in women with breast cancer) block the function of CYP2D6, and may therefore also interfere with the cancer-fighting actions of tamoxifen if they are given around the same time. The MHRA advises that:

• the SSRIs paroxetine and fluoxetine should be avoided in patients taking tamoxifen
• the use of any medicine that is known to be a strong or potent CYP2D6 inhibitor should be avoided in patients taking tamoxifen

7. Venlafaxine and risks associated with overdose

In December 2004, concerns about the potential for cardiotoxicity and toxicity in overdose with venlafaxine (Efexor) led to its restriction to specialist initiation and contraindications in patients with heart disease.

In May 2006, the MHRA concluded a review of all the latest safety evidence related to venlafaxine, particularly the risks associated with overdose. Prescribing advice for venlafaxine was updated:

• specialist supervision is needed for severely depressed or hospitalised patients who require venlafaxine doses of 300 mg daily or more
• cardiac contra-indications are more targeted towards high-risk groups
• as previously, patients with uncontrolled hypertension should not take venlafaxine, and blood pressure monitoring is recommended for all patients
• concomitant SSRI use should be restricted to specialist use
• other drug interactions are a possibility, particularly CYP3A4 inhibitors and CYP2D6 inhibitors
• these interacting drugs should only be prescribed when strictly indicated

8. SSRI/SNRI interaction with methylthioninium chloride

Methylthioninium chloride (formerly known as methylene blue) is licensed to treat a blood disorder called methaemoglobinaemia. It is also sometimes used ‘off-label’ as a visualising agent in surgical procedures or to manage uncontrollable hypotension during surgery, although these are not licensed uses.

The MHRA in 2009  investigated reports  of central nervous system (CNS) toxicity associated with methylthioninium use. All the cases occurred after the off-label use of methylthioninium as a visualising agent in parathyroid or thyroid surgery, or for the management of uncontrollable hypotension during cardiac surgery. In almost all of the cases, the patients were also being treated with serotonergic drugs (such as SSRIs and SNRIs).

After investigation, the MHRA advised that:

• there is a possibility of CNS toxicity with methylthioninium use in patients treated with serotonergic drugs such as SSRI antidepressants, the SNRI venlafaxine, and clomipramine
• intravenous methylthioninium chloride should be avoided in patients who have been treated recently with serotonergic antidepressants, including SSRIs, clomipramine, and venlafaxine

Healthcare professionals were also advised to carefully evaluate off-label use of methylthioninium chloride before starting treatment. Information on this safety issue has been added to the product information for methylthioninium chloride.   

1. luvoxamine, fluoxetine, citalopram, escitalopram, sertraline, paroxetine, venlafaxine, duloxetine, reboxetine, amitriptyline, clomipramine, dosulepin, doxepin, Imipramine, lofepramine,  nortryptiline, trimipramine, trazodone, isocarboxazid, tranylcypromine, moclobemide, phenelzine, agomelatine, vortioxetine, L-tryptophan, esketamine, mianserin, mirtazapine, zuranolone. Note that zuranolone was licensed in August 2025 and was not included in the start of the review. ↩

2. duloxetine, venlafaxine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline which are licensed in the UK. The EU review also contained milnacipran and desvenlafaxine which are not licensed in UK. ↩

3. duloxetine, venlafaxine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, amitriptyline and nortriptyline ↩