Most of the body's serotonin is made in the gut, and SSRIs such as sertraline act on serotonin. That is why an antidepressant often unsettles the stomach at first, and why the effect usually fades as the gut adjusts. SSRIs do not kill gut bacteria in the way antibiotics do, and early research points to smaller, subtler effects. Painkillers such as ibuprofen and naproxen raise the risk of bleeding from the gut when taken with an SSRI, so check before combining them. None of this is a reason to stop a prescribed antidepressant, so raise any problem with your GP or pharmacist.
Why do SSRIs affect your gut?
SSRI stands for selective serotonin reuptake inhibitor. In the UK, the most commonly prescribed are sertraline, citalopram, escitalopram, fluoxetine and paroxetine. They are used for depression and for anxiety disorders, and the NHS describes them as the most widely prescribed type of antidepressant.
They all work in the same way. When a nerve cell releases serotonin to pass on a signal, a transporter protein pumps the serotonin back into the cell for reuse. An SSRI blocks that transporter, so more serotonin stays active between cells. The medicine is aimed at the brain, but the gut runs on the same serotonin system, and the tablet reaches both.
In fact, the gut is where most of the body's serotonin is made. Cells in the gut lining release it to trigger the muscle contractions that move food along and the secretions that digest it. It also sends signals up to the brain, including the one we feel as nausea. Serotonin matters so much to digestion that medicines acting on gut serotonin are used to treat forms of IBS and to prevent nausea during chemotherapy. The gut clears serotonin away using the same transporter the brain uses.
So when you start an SSRI, more serotonin than usual is active in your gut wall. That can speed the gut up, unsettle the stomach and set off the nausea signal. Over the following weeks, the gut's serotonin receptors adjust to the new level. That is why the stomach symptoms of a new prescription usually appear early and then fade.
What gut side effects do SSRIs cause?
Nausea is the most common. A 2023 analysis pooling the results of dozens of trials found it affected roughly one person in four. The medicines also differ from each other in how much stomach trouble they cause. That is one reason a GP may suggest switching to a different SSRI rather than stopping treatment when side effects will not settle.
The other common gut effects are diarrhoea or looser stools, constipation with some of the medicines, indigestion, and changes in appetite. Feeling sick after eating in the first week or two of a new prescription is a familiar pattern, and taking the tablet with or just after food often softens it. Persistent diarrhoea after eating that carries on beyond the first few weeks is less typical, so mention it to your GP.
These symptoms usually pass. The NHS advice is to keep going for a few weeks if you can, because the early stomach effects commonly settle while the benefit builds. Never stop an SSRI suddenly, because stopping abruptly can cause withdrawal effects. If the side effects are too much, your prescriber can lower the dose gradually or look at other options with you.
Do antidepressants kill gut bacteria?
No, not in the way antibiotics do. Antibiotics are designed to kill bacteria, and what antibiotics do to the gut microbiome is fast, large and well documented. SSRIs are designed to act on human cells, not on bacteria. Any effect they have on gut bacteria is far smaller, and researchers are still working out whether it matters at all.
The idea comes from the laboratory. A 2018 study in Nature tested a large number of everyday medicines against common gut bacteria. Around a quarter of the drugs designed to act on human cells, antidepressants among them, slowed the growth of at least one bacterial species in the dish. Whether the same happens inside a person is not known. A laboratory dish is a very different place from a living gut.
There is some human evidence too. A Taiwanese study compared the gut bacteria of people with depression who were taking an SSRI, or the closely related SNRI type, with people with depression who were not. Those on the medicines had a lower variety of gut bacteria. This is early research, and it cannot prove the medicines caused the difference. People who take an antidepressant often differ from people who do not. They may be more unwell, eat differently, or take other medicines too.
The illness itself muddies the picture further. Depression and anxiety are linked with differences in gut bacteria in their own right. Pooled research led from King's College London found that people with depression and anxiety tend to carry fewer butyrate-producing bacteria, the species that ferment fibre and feed the cells lining the colon. So when a study finds a difference in someone taking an SSRI, the tablet is only one possible explanation. The signs of an imbalance in your gut bacteria are covered in a guide of their own.
Can you take ibuprofen or naproxen with sertraline or another SSRI?
Check with a pharmacist or GP first. Ibuprofen, naproxen and aspirin irritate the stomach in their own right, and taken alongside an SSRI they raise the risk of bleeding from the gut. Prescribers do sometimes use the two together deliberately, with precautions, so the combination is not banned. It simply should not happen by accident.
The reason comes back to serotonin. Platelets, the blood cells that form clots, collect serotonin from the bloodstream and use it when they clump together to stop a bleed. Most of that circulating serotonin comes from the gut, and platelets take it up through the same transporter that SSRIs block. On an SSRI, platelets can end up carrying less serotonin than usual. Researchers believe that is why a small rise in bleeding risk shows up in the data.
The risk has been measured. A large pooled analysis found that taking an SSRI on its own was linked with roughly 1.7 times the odds of a bleed in the upper gut. The absolute risk stayed small. On the authors' estimates, thousands of low-risk people would need to take an SSRI for one extra bleed to happen. In higher-risk people, such as older adults with previous stomach problems, that falls to hundreds.
Adding an anti-inflammatory painkiller changes the picture. The same analysis found the odds of an upper gut bleed rose to around four times the background level when the two were taken together. A 2022 analysis found that adding an SSRI to an existing anti-inflammatory raised the odds of a bleed by about 75% compared with the anti-inflammatory alone. The painkiller side of this is covered in our guide to how anti-inflammatory painkillers affect the stomach and gut.
In practice, mention your SSRI whenever you buy painkillers. Ibuprofen and aspirin are on open sale, so the combination is easy to stumble into without anyone noticing. If you have been prescribed both, your prescriber has weighed it up and may have added a stomach-protecting medicine, so keep taking everything as prescribed. Paracetamol does not carry this interaction. Whether it suits your pain is a question for the pharmacist at the counter.
What does the gut-brain axis have to do with antidepressants?
The gut-brain axis is the two-way communication network between the digestive system and the brain. It runs through nerves, hormones, immune signals and the chemicals gut bacteria produce. Serotonin sits in the middle of it, which is why researchers who study antidepressants have become so interested in gut bacteria.
The largest human study so far surveyed over a thousand Belgian adults, then checked its findings in a second population. Butyrate-producing bacteria were consistently more common in people reporting a higher quality of life, and two bacterial groups were depleted in people with depression. That difference remained after the researchers accounted for antidepressant use. It is an association across a population. It does not show that gut bacteria cause low mood in any one person.
Animal research suggests the traffic runs both ways. In studies in mice, certain gut bacteria prompted the gut's own cells to make more serotonin, which changed how the gut moved. Whether the same happens in people has not been shown.
The newest question in the field is whether gut bacteria influence how well an SSRI works. One small study found that people who went on to respond to SSRI treatment carried a different mix of gut bacteria beforehand than people who did not, and a 2025 study using deeper sequencing points the same way. Both studies were small, and both teams say larger trials are needed. No stool test can tell you whether your antidepressant is working or will work. That is a judgement for you and your prescriber, over time.
None of this research is a treatment, and none of it changes what is known to help with depression or anxiety now, which is talking therapies and, where appropriate, medication prescribed by your doctor. If your interest in this area comes from anxiety that arrives with digestive symptoms, our guide to anxiety after eating and the gut-brain axis looks at that overlap.
Can a gut microbiome test tell you anything useful?
Not about your mental health, and not about your medication. No stool test can diagnose depression or anxiety, measure how well an antidepressant is working, or tell you whether to take one.
What a stool test can show is which bacteria you carry, and at what levels, on the day of the sample. That includes the butyrate-producing species that appear throughout the research above. If you have taken an SSRI for a long time alongside other medicines and want a picture of where your gut bacteria stand, a gut microbiome test measures a wide range of gut bacteria from one home-collected sample. It cannot show whether a medicine caused the result, and it does not diagnose any condition. Our page on gut microbiome testing for a gut imbalance explains what a result covers and what it leaves out.
How can you look after your gut while taking an SSRI?
Keep taking your antidepressant exactly as prescribed, and never stop it suddenly. Untreated depression and anxiety carry far greater risks than an unsettled stomach, and side effects can usually be managed within treatment. With that in place, a few things help the gut side:
- Take the dose with or just after food. For many people that softens the nausea
- Give the early stomach effects a few weeks before judging them. They commonly settle just as the benefit starts to build
- Eat for the butyrate-producing bacteria that keep appearing in this research. They live on plant fibre, so a varied, plant-rich week does more for them than any single food
- Include fermented foods such as live yoghurt or kefir if you enjoy and tolerate them
- Check with a pharmacist before adding any supplement or herbal remedy. Some interact with SSRIs, and St John's wort in particular should not be taken with them
- Mention your SSRI whenever you buy painkillers or any other over-the-counter medicine, because of the bleeding interaction above
Food and testing are not treatments for depression or anxiety, and we do not present them that way. What diet can do is support your gut while your prescription does its job. For the fuller detail, see our guide to the best foods for gut health and why they help.
When should you see a GP?
SSRIs slightly reduce the blood's ability to clot, so on this medicine the signs of bleeding from the gut matter more than any other gut symptom. Contact your GP the same day, or ring NHS 111 when the surgery is closed, if you notice:
- Black, tarry or sticky stools, particularly if you also take anti-inflammatory painkillers, aspirin or a blood thinner
- Blood in your stool, or bleeding when you go to the toilet
- Vomiting blood, or vomit that looks like ground coffee
- Unusual bruising, or bleeding that takes longer than normal to stop
Vomiting blood or passing black, tarry stools needs emergency assessment. Call 999 or go to A&E straight away.
The general gut warning signs still apply while you are taking an SSRI, and each needs a GP appointment in its own right: a change in bowel habit lasting more than three weeks, unexplained weight loss, difficulty swallowing, persistent vomiting, severe or persistent stomach pain, and new digestive symptoms over the age of 50 or with a family history of bowel or ovarian cancer. Gut side effects that are not dangerous but are not settling are also a reason to book in, because options such as changing the dose timing or switching to a different SSRI do not mean giving up treatment.
Your mental health has its own red flags. If your mood gets worse after starting or changing an antidepressant, or you have thoughts of harming yourself, contact your GP urgently or call NHS 111. If you feel unable to keep yourself safe, call 999 or go to A&E. The Samaritans are free to call on 116 123, at any time, from any phone. In England you can also refer yourself directly to NHS talking therapies for anxiety and depression without going through your GP first.
This guide is for information only and does not replace medical advice. Speak to your GP or pharmacist about your own treatment.
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