Starting a GLP-1 While on Antidepressants? Read This First

Posted on August 28, 2026 by

According to the Office for National Statistics (ONS) in 2025, as many as 18% — nearly 1 in 5 people — in the UK are diagnosed with depression. Once noted to be a short-term medication, around 2 million people are now taking antidepressants for five years or more.

Depression and anxiety are far more than just feeling sad or nervous. Research highlights everything from brain chemistry to gut microbiome composition as potential causes of these conditions.

This becomes more interesting when conditions such as obesity are added and, of course, how GLP-1s like Wegovy and Mounjaro will impact all of those delicate systems. This is why, if you have depression and anxiety and want to engage in medicated weight loss, you need clinical expertise to ensure it is as seamless as possible.

At the Bodyline Clinic, we have helped over 100,000 people across the UK to hit their weight loss goals over the last 18 years. We are also composed of a multidisciplinary team who are involved in clinical research into GLP-1s, offering clinical trials and expertise. So, in short, we know what we are doing and pride ourselves on being able to offer those rejected for GLP-1s from pharmacies a potential chance at weight loss with this method.

How GLP-1s and Antidepressants Work

When drugs interact negatively with each other, it is usually because they impact the same parts of the body. So, let's have a quick biology lesson.

GLP-1s

GLP-1s, like semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro), are peptides. When they are ingested orally or injected, they are broken down through the body's general protein-clearing pathways. Crucially, these medications are not broken down through the liver (or by the CYP450 enzyme), which is where most drug interactions occur. One drug will build up over another due to competing for the same enzyme — this is how someone can get unwell from taking two medications.

Antidepressants

The two groups of antidepressants we are talking about here are selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, and serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine and venlafaxine.

These drugs are cleared in the liver by the CYP450 enzyme. So, an SSRI or an SNRI and a GLP-1 will barely overlap at a chemical level in the body.

So, What's the Problem?

At this stage, you may be confused. You may have approached an online pharmacy only to be told that you aren't suitable for GLP-1s due to taking an SSRI. If they aren't contraindicated, why was that the response you got?

Slower Gastric Emptying

GLP-1 medications, such as Wegovy or Mounjaro, have the side effect of delayed gastric emptying. They slow down how fast your stomach empties into the small intestine, especially when you have just started or in the first week of a new dosage.

So, in theory, this will likely have an impact on how fast an oral antidepressant is absorbed. A study by Granhall et al. (2019) explored semaglutide and noted that it delayed the time to peak concentration of co-administered oral drugs. However, it did not change the total amount that was absorbed.

Many people who take SSRIs are also on anti-seizure medications or mood stabilisers. It is worth noting that a GLP-1 will probably have an impact on those too. At the time of writing, there is no clear data which highlights how many people are taking a mood stabiliser alongside an SSRI. What we do know is that 4.0% of people with newly diagnosed bipolar disorder in the UK were prescribed lithium and an antidepressant as their first treatment combination, according to a 2022 study from Cambridge University.

The Side Effects

When you start taking weight loss medication like Wegovy, you will experience side effects. If you start both GLP-1s and antidepressants at the same time, you will likely experience nausea. When you are increasing the dosages at the same time, the nausea can become serious.

Is nausea overly serious? No, not really, but it can become extremely difficult to ignore and can increase the likelihood of you giving up on one or both medications. There is some good news, though. Nausea with both antidepressants and GLP-1s is one of the most studied areas and is considered more manageable with slower titration of the GLP-1s and smaller meals.

There are a few other linked side effects. Both GLP-1s and SSRIs can cause:

• Loose stools/diarrhoea
• Constipation
• Blunted appetite/not feeling hungry
• Fatigue
• Headaches

None of these symptoms is dangerous and they are usually temporary. However, they can make taking these medications more complex, more so when you are starting both or increasing/decreasing one at the same time. This kind of management requires clinical care that online prescribers simply cannot offer.

Serotonin Syndrome

Serotonin syndrome is a dangerous buildup of serotonin in the body, usually when two or more serotonergic drugs are combined. GLP-1s are not classically serotonergic drugs, so a GLP-1 plus an SSRI is not a typical high-risk combination. However, the bigger serotonin syndrome risk in someone taking SSRIs comes from other agents, like bupropion combined with another serotonergic drug, or adding a second serotonergic drug on top of an SSRI. There is also the risk that, due to slower gastric emptying, some medications may build up, which may lead to dangerous levels of serotonin accumulation.

Minor to moderate signs of serotonin syndrome include:

• Nervousness and agitation
• Nausea and vomiting
• Diarrhoea
• Dilated pupils
• Shakiness or tremor
• Muscle twitching, spasms and rigidity

More severe signs of serotonin syndrome include:

• Confusion, disorientation and delirium
• Tachycardia, or a rapid heart rate
• High blood pressure
• High body temperature (greater than 38.5°C / 101.3°F)
• Seizures
• Fainting or collapsing

If you notice these symptoms while taking a GLP-1 and an SSRI, call 999 immediately.

Clinical Studies and Depression

Clinical studies into GLP-1 treatment routinely exclude people from their studies if they have a history of extreme depression, major depressive disorder or suicidal ideation. For studies into Wegovy, Ozempic and Mounjaro long-term side effects, people who fit these criteria are routinely excluded from pivotal Phase 3 randomised controlled trials. But why?

• Researchers need to ensure that any side effects or mood changes that occur in their studies are due to the GLP-1s, rather than underlying depression or other mental health issues.
• Many severe psychiatric issues can cause secondary safety risks. These would require specialised monitoring and interventions that the standard drug trial is not able to oversee.
• Those who have psychiatric issues may be more prone to dropping out of studies or, in self-report studies, misreporting their symptoms. This creates incomplete data sets and can skew data in one direction or another.

So, the long and the short of it is that we don't have data on how these medications may interact with people who have these disorders. As a result, pharmacies and online GPs will not give the green light to those with them to take weight loss medications.

GLP-1s and Mood

If you are taking an SSRI or an SNRI, you will want to know if taking a GLP-1 will cause you to have a worse mood long-term. As we have mentioned in our piece on Obesity and Alcohol Misuse, a core brain mechanism that is impacted is dopamine. As GLP-1s seem to cause dopamine levels to lower, this begs the question of whether taking GLP-1s can impact the mental health of those taking them.

The research is mixed in this area. A study from 2024 noted that GLP-1s like semaglutide can decrease feelings of depression. Looking at the STEP trials of semaglutide 2.4mg, which used the Patient Health Questionnaire-9 (PHQ-9) as its screening tool for depressive symptoms, the study found no statistically significant increase in depressive symptoms. Indeed, participants had a small but statistically significant reduction in depressive symptoms.

However, looking more closely at this study, we notice something a bit unusual. Around 15% of the participants taking semaglutide were taking an antidepressant or a similar psychiatric medication. 8.6% were taking SSRIs, and those who took semaglutide (versus placebo) had an 8.2% improvement in their PHQ-9 scores. Yet, the study did not report whether those who improved were specifically those taking antidepressants.

On the other side of the fence, a 2025 study from the Diabetes, Obesity and Metabolism Journal points to a potential worsening of mental health issues when taking GLP-1s. However, this study has a few things worth noting:

• Unlike the 2024 study on semaglutide, there were no clinically validated questionnaires to measure depressive symptoms.
• This study was observational — participants reported how they felt.
• Three different GLP-1s were examined (semaglutide, tirzepatide and liraglutide). Across the groups, there was no significant difference in rates of depressive symptoms developing.

When looking to clinical, double-blind studies for insight, no evidence points to GLP-1s increasing the risk of depression or suicidal behaviour. However, as highlighted earlier, these trials exclude those who may have significant or potentially unstable psychiatric disorders.

Mental Wellbeing with Bodyline

Our team at the Bodyline Clinic are not your standard online pharmacy. We have over 18 years of expertise in helping people to hit their weight goals. We are also involved in clinical research into GLP-1s and have an exceptional clinical team behind us. We personalise each weight loss journey and aim to help those who may need specialised clinical care, such as those taking antidepressants.

So, if that sounds good, contact our team today for a free consultation and let's get your weight loss journey started.

FAQs

Can I Take GLP-1 Medications if I Am Taking an SSRI?

These medications are not contraindicated, but there is very little research that looks at groups who fit the criteria for depression taking GLP-1s. However, our team at Bodyline will provide specialised care to help you stay motivated and monitor your mood.

Will Taking Both Medications at the Same Time Worsen My Mood?

There is no notable evidence that suggests that if you take an SSRI and a GLP-1 at the same time, it will negatively impact your mood. However, if you do experience this on your weight loss journey with our team, please tell us and we will aim to find a solution.

Will I Need Closer Monitoring?

It depends. The clinical assessment made by our team will help us determine how severe your mental health issues are and how much monitoring you will need when taking GLP-1s.