select search filters
briefings
roundups & rapid reactions
Fiona fox's blog
Different antidepressants vary widely in their physical side effects, according to a systematic review and meta-analysis published in The Lancet. The study found that some antidepressants are linked to weight gain in nearly half of patients, while others are associated with weight loss in over half. Certain drugs can also raise or lower heart rate and blood pressure. The authors emphasise that these findings should not deter people from taking antidepressants, but highlight the importance of tailoring treatment to each individual, taking into account their personal health and preferences.
The All Ireland Science Media Centre asked local experts to comment.
Dr Brian O’Donoghue, Professor of Psychiatry, University College Dublin, comments:
“This is an important study by Pillinger and colleagues that compared the side effects of 30 different antidepressant medications by combining over 150 studies, which included more than 58,000 participants in total.
“The effectiveness of different antidepressant medications that are used as first line treatments for depression or anxiety do not vary substantially. Therefore, the selection of antidepressant medication should be based on the anticipated side-effects. This review by Pillinger et al helps inform individuals about the likely side-effects associated with each antidepressant medication, which in turn will facilitate making an informed decision about which antidepressant medication is most suitable. For example, the study highlights that different antidepressants have varying effects on weight gain, heart rate, blood pressure, cholesterol and blood glucose levels. Therefore, individuals with pre-existing conditions, vulnerabilities from family history of certain disorders or if they have a concern about a specific side effect, they can now make a more informed and individualised decision in relation to what antidepressant medication would be best suited for them.
“Although not mentioned in the article, members of this research group have also developed an online tool that can be used, in consultation with a clinician, to support people to make an informed decision about selecting an antidepressant medication; www.psymatik.com“
Professor Frank Moriarty, Associate Professor, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, comments:
“This review of evidence was conducted in a thorough way, and notably, the researchers looked at sources where unpublished trials might be found. This is important as previous work has shown that not all antidepressant trials have been published, and focusing on only the published research can skew the evidence.
“These findings do not show major new physical side effects of antidepressants, and so should not be a cause for concern. Rather the results should help to personalise the choice of therapy for patients starting on antidepressant medicine. They may also help tailor advice and monitoring of side effects, going beyond the overall drug class effects. However it is worth bearing in mind that these are the average effect in groups of patients, and so there may be differences between individuals in their experience of using a medicine. If a patient thinks they may be experiencing a side effect of their medicine, they should let their healthcare professional know and discuss this with them.
“For patients and their healthcare professionals in Ireland, most of the medicines identified as having strongest side effects, e.g. the biggest decrease in heart rate or increase in blood pressure, are older drugs that are used less often, or only when other medicines have not been effective.
“It’s also important to bear in mind that this study only looked at physical side effects of these medicines. It does not provide any evidence on their possible benefits, nor on other possible harms, including the effects when a patient stops taking these medicines. These factors, as well as non-drug treatment options where available and accessible, are important for patients to discuss with their prescriber in making a decision to start an antidepressant.”
Professor Keith Murphy, Professor of Neuropharmacology, University College Dublin, comments:
“In a very recent meta-analysis published this week in The Lancet, Pillinger and colleagues (2025) report the first comprehensive comparative review of how different antidepressants affect the body beyond the central nervous system and their mood-related benefits. They analysed data from over 58,000 participants across 151 clinical trials, and report clear differences between antidepressant drugs in their effects on weight, blood pressure, heart rate, and metabolism, factors with important impacts on cardiovascular health. Tricyclic antidepressants and certain SNRIs (serotonin and noradrenaline reuptake inhibitors), such as amitriptyline, venlafaxine, and duloxetine, were associated with, for example, increased heart rate and blood pressure. In contrast, medications like agomelatine and bupropion appeared to have fewer measurable physiological effects. While most of these effects were relatively small over the short term, they have the potential to become more significant with long-term use, especially for people already at risk of cardiovascular disease.
“These findings have potentially important implications for prescribing practice in Ireland, where antidepressant use is relatively high by European standards. At present, doctors generally monitor weight and blood pressure, but systematic checks for other metabolic changes are not routine. The results of this new study suggest that a more structured approach may be beneficial, perhaps similar to the monitoring already recommended for antipsychotic medications. Regular reviews of weight, blood pressure, and blood tests for glucose and cholesterol could help identify early signs of metabolic disturbance. This would be particularly useful in patients on higher-risk drugs or long-term treatment.
“The research highlights the potential for physical side effects of antidepressants. It is essential, however, to note that the appropriate use of these medicines remains effective and generally safe. The Lancet study reinforces the importance of open discussion between patients and prescribers about the mental health benefits and the potential physical side effects of antidepressants. Such dialogue can ensure that antidepressant treatment decisions can be best tailored to support the whole person’s wellbeing.”
Dr Dervla Kelly, Associate Professor, School of Medicine, University of Limerick, comments:
Do antidepressants cause weight gain and increase risk of heart problems?
“Results from a new systematic review of 30 different antidepressant medicines suggest that some antidepressants may cause problematic weight gain and heart problems. Antidepressants are available by prescription and have proven to be effective in treating depression. Beyond depression, they have proven useful in other conditions such as anxiety, OCD, eating disorders, incontinence and chronic pain. Because there are lots of antidepressant to choose from, it is really important to have comparative studies like this to differentiate between antidepressants, in terms of side effects.
“It has been known for some time that certain antidepressants cause weight gain and others may be unsafe for people with chronic heart disease and arrythmias. It is also accepted that people with diabetes need to monitor their blood glucose more closely and may need to adjust their diabetes medications when taking an antidepressant. This new study brings back to the spotlight the side effects of antidepressants.”
What is known about the link between antidepressants and weight gain?
“Regarding weight gain, 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. We know from previous research than antidepressants paroxetine, mirtazapine and amitriptylline are associated with increased weight gain. The new study calls out maprotiline as having the worst effect on weight, however this drug is not routinely used in Ireland.
“Weight gain, cholesterol and metabolic changes are typically a gradual health issues, where small changes over time can, sometimes without symptoms, can lead to health problems. The duration of a randomised controlled trial (3-12 weeks in this study) may not always give time to monitor for these issues.”
What is known about cardiovascular health and antidepressants?
“Heart problems previously linked with antidepressants include increased heart rate, arrhythmia, conduction problems, hypertension and postural hypotension. Indeed, guidelines currently recommend sertraline as the first line treatment for people with existing cardiovascular problems. While tricyclic antidepressants, duloxetine, reboxetine, and venlafaxine and citalopram and escitalopram are less preferred or generally avoided in people with heart disease.
“In this study, amitriptyline, venlafaxine, fluoxetine and duloxetine are associated with increased blood pressure compared to placebo. However, it is important to be cautious when interpreting the study findings as 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. 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.”
So given all of this, should people worry about how safe antidepressants are?
“This new study should not create a 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.
“Given how common heart disease and heart disease risk factors are, such as high blood pressure, obesity and diabetes (which are often unrecognised), it is important to select antidepressant treatments, considering an individual’s weight, cardiovascular health status, family history and lifestyle factors.
“Sometimes the cardiovascular side effects may be dose related and a baseline test a called an ECG may be used in people with cardiac disease before starting them on antidepressants such as citalopram or escitalopram.
“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. This study suggests that weight, cholesterol, blood pressure, blood sugars may need to be routinely monitored when people are taking antidepressants. It’s important to talk with your pharmacist or doctor if you have questions about taking an antidepressant you’ve been prescribed.”
Declared interests:
Dr Brian O’Donoghue: No conflicts of interest, except that I have collaborated with researchers involved in this study.
Professor Frank Moriarty: My research focuses on the effects of reducing or stopping medications, and is funded by national research funders or charitable foundations (Health Research Board, Wellcome Trust). I have no other conflicts of interest.
Prof Keith Murphy: No conflicts of interest.
Dr Dervla Kelly: Nothing to declare.