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New research published in The Lancet in November 2025 has found that antidepressants vary widely in how they affect the body. The large-scale study reviewed data from more than 58,000 people across 150 clinical trials, comparing 30 different antidepressants and their short-term effects (typically over eight weeks).
The researchers found that some antidepressants can cause problematic changes in body weight, heart rate and blood pressure within just a few weeks, whereas others don’t have any significant physical effects.
The study’s authors are calling for antidepressant treatment guidelines to be updated to reflect these findings, highlighting the importance of individualised prescribing.
People with pre-existing conditions (such as heart disease) or a family history of certain disorders, or who are worried about specific side effects of their medicines, should be making an informed choice about which antidepressant is most suitable for them.
“Antidepressants are among the most widely used medicines in the world,” says Dr Toby Pillinger, academic clinical lecturer at the Institute of Psychiatry, Psychology and Neuroscience, consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, and the study’s senior author.
“While many people benefit from them, these drugs are not identical. Some can lead to meaningful changes in weight, heart rate and blood pressure in a relatively short period.
Our findings show that SSRIs, which are the most prescribed type of antidepressant, tend to have fewer physical side-effects. But, for others, closer physical health monitoring may be warranted. The aim isn’t to deter use, but to empower patients and clinicians to make informed choices and to encourage personalised care.”
Treating depression
Depression affects nearly one in six people in the UK at some time in their life. Even when it is considered ‘less severe’, depression can negatively affect a person’s work, social life and relationships. More severe depression can be disabling.
With the right treatment and support, people with depression can usually manage their symptoms and make a good recovery. However, despite its high prevalence, depression is often under-treated.
This is because many people are unwilling to seek help, they worry about taking antidepressants (especially long-term) or see their GP about physical symptoms associated with depression, rather than the underlying mental health issues.
The National Institute for Health and Care Excellence (NICE) guideline on the treatment and management of depression in adults states that healthcare professionals should help people with depression choose the treatment that suits them best, explain the benefits and risks, and offer ongoing support and check-ups.
For some people, especially those with moderate to severe depression, antidepressants can be an effective and necessary first choice.
“While evidence shows that antidepressants can be a safe and effective treatment for some patients, like any medication, they are not without side effects, which can vary from patient to patient,” says professor Kamila Hawthorne, chair of the Royal College of GPs.
“If a decision is made to prescribe medication, patients should be reviewed by their GP two to three weeks later to check for side effects. There should then be regular medication reviews to consider whether the treatment is still optimal, whether it’s having any side effects, and whether to reduce the dosage or stop taking medication altogether.”
According to the NICE guideline on depression in adults, people with less severe symptoms should be offered psychological therapies (talking treatments) as a first-line management approach, rather than antidepressants.
However, the availability of talking therapies on the NHS varies across the country and antidepressant prescribing continues to rise.
“While antidepressants are evidence-based and effective for some patients, we also need to see much greater investment in alternative treatments, such as talking therapies,” says professor Hawthorne. “
These have been shown to be effective, but patients are facing long waiting lists, and current service provision is patchy.”
“The results underscore the need for routine physical health checks in those treated with antidepressants”
Antidepressant prescribing
In 2024/25, around 8.89 million people were prescribed antidepressants in England alone, and it is estimated that around a third of these medicines were newly prescribed.
At the end of October 2025, the New Medicine Service (NMS) in pharmacies was expanded to include medicines for depression under the 2025/26 funding deal.
This means that people aged 18 years and over who are newly prescribed the most common antidepressants will be able to seek additional advice and support from their local pharmacist about their medicines, healthy lifestyle changes, and understanding their treatment options.
According to the Lancet study, it is important to tailor antidepressant treatment to each patient, taking into account their health and individual preferences.
Antidepressants work by increasing levels of brain transmitters such as serotonin and noradrenaline, which are linked to mood and emotion.
Their side effects are mild for most people and usually wear off over a couple of weeks. However, some antidepressants are more likely to cause side effects in certain people or may not be suitable due to the person’s underlying medical conditions.
What the study says
In the Lancet study, the antidepressants showed different effects on weight, blood pressure, heart rate and metabolism, all of which are important risk factors for heart disease, diabetes and many other long-term conditions.
The researchers found that some antidepressants (e.g. maprotiline and amitriptyline) were associated with weight gain in almost half of patients prescribed them, while another antidepressant (agomelatine) was instead associated with weight loss in 55 per cent of patients.
The researchers also found that there was a difference of more than a 20 beats-per-minute in heart rate when taking different antidepressants, and a difference of over 10mmHg variation in blood pressure.
Most antidepressants did not show major effects on kidney or liver function, electrolyte levels, or heart rhythm.
“It is thought that the neurotransmitters dopamine and noradrenaline, which can be altered by antidepressants, are also involved in the regulation of appetite, satiety, craving, and eating behaviours,” says Dervla Kelly, associate professor at the School of Medicine at the University of Limerick.
“We know from previous research that the antidepressants paroxetine, mirtazapine and amitriptyline are associated with increased weight gain. Weight gain, cholesterol and metabolic changes are typically gradual health issues, where small changes over time can – sometimes without symptoms – lead to health problems.”
It still isn’t known whether antidepressant-induced physical effects like these persist or change over time. More research is needed to understand how the medicines affect the body in the long term and whether any changes could be significant for people who are already at a higher risk of certain diseases.
“This finding is particularly important for individuals with pre-existing conditions like heart disease or diabetes,” says professor Azeem Majeed, chair of primary care and public health and head of department at Imperial College London.
“For patients and clinicians, the results underscore the need for routine physical health checks in those treated with antidepressants. Moreover, awareness of these side effects is essential to support shared decision-making about the risks and benefits of treatment with antidepressants.”
Regular monitoring
Dr Kelly stresses that these discoveries should not create panic about the safety of antidepressants. “For patients with existing obesity or heart problems, the findings from the study are an important piece of information for prescribers to have to hand,” she says.
“Once someone is started on these medicines, they need to have follow-up monitoring to check blood pressure, blood sugars and cholesterol. How often monitoring takes place can vary a lot for people, often depending on their doctor.”
Patients certainly should not stop taking antidepressants without medical advice and the support of an experienced healthcare professional.
Stopping these medicines abruptly, missing doses or not taking a full dose can lead to withdrawal symptoms.
In July 2025, researchers at Imperial College London, King’s College London, UCL and UK collaborators found that most people do not experience severe withdrawal when they stop taking most antidepressants after long-term use.
The most common withdrawal symptoms in this review (published in JAMA Psychiatry) were dizziness, nausea, vertigo and nervousness.
This followed research led by UCL researchers (published in Psychiatry Research in May 2025), which found that people who have been taking antidepressants for more than two years are 10 times more likely to experience withdrawal symptoms when they come off the medicines, compared to people who have been taking antidepressants for less than six months.
Dr Kelly says that while the Lancet research results are important, they should be treated with some caution until they are confirmed with further research studies.
“Sometimes cardiovascular problems that coincide with antidepressant use could be influenced by behavioural or lifestyle factors associated with depression, such as delayed healthcare-seeking and poor cardiovascular health,” she says.
“In addition, randomised controlled trials typically recruit younger adults without other illnesses, so this study likely does not reflect the risks of antidepressant use in practice, where they are prescribed in people with other illnesses.”
Alternatives to antidepressants
Alternatives to antidepressants
According to NHS England’s Decision support tool: making decisions about managing depression, depression affects people in different ways, so not everyone needs to take antidepressants to manage their symptoms. Other management approaches, recommended for less severe depression or to use alongside antidepressants in more severe cases, include:
1. Active monitoring: lifestyle changes, such as regular exercise, healthy eating, giving up smoking, cutting down on alcohol, getting enough sleep and taking up hobbies such as dance and gardening, can help to improve a person’s mood and overall wellbeing
2. Exercise programmes: some sports and exercise sessions are specifically aimed at people with depression and other mental health problems
3. Guided self-help: this is a form of cognitive behavioural therapy (CBT). People can use self-help guides such as books, computer programmes and self-help apps with the support of a therapist online, over the phone or in person
4. Talking therapies, including CBT: these can be part of a group session or
one-to-one counselling. Talking therapies are available on the NHS for anxiety and depression, but not in all parts of the country
5. Mindfulness or meditation: can again be undertaken in a group, one-to-one with a practitioner or using apps such as Headspace
6. St John’s Wort: research shows that the herbal remedy St John’s Wort may help less severe depression, but it is important to explain the risk of side effects, that product quality varies significantly, and there is a chance of potentially serious drug interactions (e.g. with hormonal contraceptives, anticoagulants and anticonvulsants)
7. Light therapy: may help people with winter depression, which is also known as seasonal affective disorder (SAD).
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