Jump to: What does UK guidance say? | Are there any indirect effects to be aware of? | Can Wegovy affect your mood? | Practical tips for taking both medications | Frequently asked questions | Take home message
You can take Wegovy (semaglutide) with sertraline. The UK Summary of Product Characteristics (SmPC) for Wegovy and the British National Formulary (BNF) list no direct pharmacokinetic interactions between semaglutide and antidepressants, including SSRIs like sertraline.1
The reason there’s no direct interaction comes down to how each drug is processed by your body. Wegovy is broken down through proteolytic cleavage (similar to how your body breaks down proteins), while sertraline is metabolised by liver enzymes (cytochrome P450).1 Because they use completely different pathways, they don’t compete or interfere with each other.
That said, both medications can cause gastrointestinal side effects like nausea, so you may notice these are more pronounced when starting Wegovy while already on sertraline. This typically settles as your body adjusts.
If you’re considering Wegovy while taking sertraline, it’s worth letting both your GP and prescribing pharmacist know about all your medications so they can monitor your progress.
Important safety information: Wegovy (semaglutide) is a prescription-only medication for managing obesity in adults with a BMI of 30 or above, or 27 or above with weight-related health conditions. This article is for informational purposes only. Always consult with your healthcare provider before starting any new medication, particularly if you’re taking antidepressants or have other health conditions.
What does UK prescribing guidance say about Wegovy and sertraline?
The official UK prescribing information for Wegovy doesn’t list any clinically relevant interactions with antidepressant medications.1
This is largely because of how differently these medications work in your body:
- Wegovy is a peptide-based medication that mimics the gut hormone GLP-1. It’s broken down by enzymes that digest proteins, not by liver enzymes.
- Sertraline is processed primarily by cytochrome P450 enzymes in the liver, particularly CYP2B6, CYP2C19, and CYP3A4
Because they don’t share metabolic pathways, there’s no competition for the same enzymes and therefore no direct drug-drug interaction.1
The same applies to other commonly prescribed SSRIs, like citalopram, fluoxetine, and escitalopram, as well as SNRIs, like venlafaxine and duloxetine.1
What the prescribing information does mention
While there’s no direct interaction with sertraline, the Wegovy SmPC does note that semaglutide delays gastric emptying, which could theoretically affect the absorption of some oral medications.1
However, this is primarily a concern for medications with a narrow therapeutic index (where small changes in blood levels can cause problems) or those that require rapid absorption for effectiveness.
Sertraline doesn’t fall into either category. It has a relatively wide therapeutic window, and its effectiveness doesn’t depend on rapid absorption. Any minor changes in how quickly it’s absorbed are unlikely to affect how well it works.
Are there any indirect effects to be aware of?
While Wegovy and sertraline don’t interact directly, there are some practical considerations worth knowing about.
Shared side effects
Both medications can cause gastrointestinal symptoms:
| Side effect |
Wegovy |
Sertraline |
| Nausea |
Very common (affects more than 1 in 10 people) |
Common (affects up to 1 in 10 people) |
| Diarrhoea |
Very common |
Common |
| Reduced appetite |
Common |
Common |
| Constipation |
Common |
Common |
When you’re taking both medications, these effects might be additive, particularly nausea. This is most likely during the first few weeks of starting Wegovy or when your dose increases.
The good news is that Wegovy’s gastrointestinal side effects typically improve over time. In the STEP clinical trials, the proportion of people experiencing nausea dropped significantly after the first few months of treatment.2
Weight and mood: a connected relationship
There’s a well-established link between obesity and mental health conditions like depression. Research suggests that people living with obesity are at higher risk of developing depression, and vice versa.3
Losing weight can have positive effects on mood and mental wellbeing, which may complement the effects of your antidepressant medication. However, it’s important not to reduce or stop your sertraline without discussing this with your doctor, even if you’re feeling better.
Can Wegovy affect your mood?
This is an area of active research, and the evidence is mixed. Here’s what we know so far.
Evidence suggesting potential benefits
A 2024 systematic review and meta-analysis of six studies involving 2,071 participants found that people treated with GLP-1 medications showed significant reductions in depression rating scale scores compared to control groups.4
A 2025 systematic review examining GLP-1 receptor agonists for depression found that several observational studies showed reduced depressive symptoms in people taking these medications, though results from randomised controlled trials were more mixed.5
These benefits might come from several factors:
- Weight loss itself improves mood and self-esteem
- Reduced inflammation (which is linked to depression)
- Direct effects on GLP-1 receptors in the brain, which are present in areas involved in mood regulation
- Improved physical function and mobility
- Healthier eating habits developed while on the medication
Evidence suggesting caution is needed
However, pharmacovigilance studies (which analyse reports of side effects submitted to drug safety databases) have identified signals for psychiatric adverse events with GLP-1 medications, including semaglutide.
A 2024 pharmacovigilance analysis of a global drug safety database found that GLP-1 receptor agonists, including semaglutide, had reporting-odds ratios suggesting associations with depression, anxiety, and, in rare cases, suicidal ideation.6 However, pharmacovigilance data can’t prove causation, as it reflects reports rather than controlled studies.
Several case reports have described individual patients developing or experiencing worsening depression temporally associated with semaglutide use.7,8
In one notable case, a patient with no prior psychiatric history developed depressive symptoms and was subsequently treated with sertraline while semaglutide was discontinued, with improvement noted.9
A large meta-analysis of randomised controlled trials published in 2024 found no significant overall association between GLP-1 medications and psychiatric disorders, but the authors noted that ongoing monitoring is advisable.10
What this means for you
The relationship between weight loss medications and mental health is complex. The current evidence doesn’t suggest you should avoid Wegovy if you’re taking sertraline, but it does highlight the importance of:
- Continuing your prescribed antidepressant treatment
- Monitoring your mood, particularly in the first few months
- Keeping your GP informed about any changes in how you’re feeling
- Not stopping sertraline without medical advice, even if you feel your mood has improved
Practical tips for taking both medications
If you’re taking sertraline and starting Wegovy, here are some practical suggestions.
Timing your medications
There’s no specific requirement to take Wegovy and sertraline at different times. Wegovy is a once-weekly injection that can be taken at any time of day, with or without food.1
Sertraline is typically taken once daily, often in the morning. You can continue your usual routine.
Managing nausea
If you experience increased nausea when starting Wegovy:
- Eat smaller, more frequent meals rather than large portions
- Avoid or limit ultra-processed foods and takeaways
- Stay well hydrated with small, regular sips of water
- Ginger tea or ginger supplements may help
- Speak to your pharmacist about anti-nausea options if needed
For more detailed guidance on managing side effects, see our guide to Wegovy side effects.
When to contact your healthcare provider
Get in touch with your GP or prescribing pharmacist if you experience:
- Persistent nausea or vomiting that prevents you from eating or drinking
- Significant changes in your mood, including increased anxiety or low mood
- Thoughts of self-harm (seek immediate help)
- Severe abdominal pain
- Any other symptoms that concern you
Keep all prescribers informed
Make sure both your GP (who prescribes your sertraline) and your weight loss medication prescriber know about all the medications you’re taking. This helps ensure coordinated care and allows them to monitor you appropriately.
Frequently asked questions
Will Wegovy make my sertraline less effective?
No. There’s no evidence that Wegovy affects how well sertraline works. While Wegovy does slow gastric emptying, this doesn’t significantly impact sertraline absorption or effectiveness.1
Should I take Wegovy and sertraline at different times of day?
There’s no requirement to separate them. Wegovy is a weekly injection, and sertraline is typically taken daily. You can continue your usual sertraline schedule without adjusting for Wegovy.
Can antidepressants affect how well Wegovy works for weight loss?
A 2022 study published in JAMA Network Open found that people taking antidepressants experienced somewhat reduced weight loss with GLP-1 medications compared to those not taking antidepressants.11
However, this doesn’t mean Wegovy won’t work for you. It simply means that weight loss outcomes may vary, and your prescriber can help set realistic expectations.
What if my nausea gets worse when I start Wegovy?
Some increased nausea is common when starting Wegovy and usually improves over the first few weeks. Try eating smaller meals, avoiding ultra-processed foods, and staying hydrated. If nausea is severe or prevents you from eating, contact your prescriber.
Can I come off sertraline if I lose weight and feel better?
Never stop or reduce your antidepressant without discussing it with your doctor first. While weight loss can improve mood, stopping sertraline abruptly can cause withdrawal symptoms and potentially a return of depression.
Any changes to your antidepressant should be gradual and medically supervised.
Will weight loss improve my depression?
Weight loss can positively affect mood and mental wellbeing for many people. However, depression is a complex condition with many contributing factors, and weight loss alone isn’t a treatment for clinical depression.
What about other antidepressants besides sertraline?
The same principles apply to other SSRIs (citalopram, fluoxetine, escitalopram, paroxetine) and SNRIs (venlafaxine, duloxetine). There are no listed direct interactions with Wegovy.1
If you’re taking a tricyclic antidepressant or MAOI, it’s still worth checking with your prescriber, though no specific interactions are documented.
Should I tell my GP I’m taking Wegovy?
Yes. Your GP must know about all medications you’re taking, including private prescriptions. This ensures they can provide coordinated care and monitor for any issues.
What if my mood changes while taking Wegovy?
Monitor how you’re feeling and report any significant mood changes to your healthcare provider. While the evidence is mixed, some people may experience mood changes on GLP-1 medications.
Continuing your antidepressant and maintaining open communication with your prescribers is the best approach.
Take home message
You can safely take Wegovy alongside sertraline. UK prescribing guidance confirms no clinically relevant direct drug interactions between semaglutide and SSRI antidepressants.1
The main practical consideration is that both medications can cause gastrointestinal side effects, which may be more noticeable when you first start Wegovy. These typically improve with time.
While research on GLP-1 medications and mental health is ongoing, the current evidence doesn’t suggest avoiding Wegovy if you’re taking antidepressants.
However, it’s important to continue your sertraline as prescribed and keep your healthcare providers informed about any mood changes.
If you’re considering Wegovy while taking sertraline, speak with both your GP and weight loss medication prescriber to ensure coordinated, safe care.
Second Nature's Mounjaro and Wegovy programmes
Second Nature provides Mounjaro or Wegovy as part of our Mounjaro and Wegovy weight-loss programmes.
Why choose Second Nature over other medication providers, assuming you're eligible?
Because peace of mind matters.
We've had the privilege of working with the NHS for over eight years, helping people across the UK take meaningful steps toward a healthier, happier life.
Our programmes are designed to meet people where they are, whether that means support with weight loss through compassionate one-to-one health coaching, or access to the latest weight-loss medications (like Mounjaro and Wegovy) delivered alongside expert care from a multidisciplinary team of doctors, psychologists, dietitians, and personal trainers.
At the heart of everything we do is a simple belief: real, lasting change comes from building better habits, not relying on quick fixes. We're here to support that change every step of the way.
With over a decade of experience, thousands of lives changed, and a long-standing record of delivering programmes used by the NHS, we believe we're the UK's most trusted weight-loss programme.
We hope to offer you something invaluable: peace of mind, and the support you need to take that first step.
References
- Electronic Medicines Compendium. (2024). Wegovy Summary of Product Characteristics (SmPC).
- Wilding, J.P., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384(11), 989-1002.
- Luppino, F.S., et al. (2010). Overweight, Obesity, and Depression: A Systematic Review and Meta-analysis of Longitudinal Studies. Archives of General Psychiatry, 67(3), 220-229.
- Chen, X., et al. (2024). The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. American Journal of Geriatric Psychiatry, 32(1), 117-127.
- Mansur, R.B., et al. (2025). Repurposing GLP-1 receptor agonists for depression: a systematic review. Progress in Neuro-Psychopharmacology & Biological Psychiatry.
- Martins, T., et al. (2024). Psychiatric adverse events associated with GLP-1 receptor agonists: Disproportionality analysis of a global pharmacovigilance database. Frontiers in Endocrinology, 15, 1330936.
- Faour, M., et al. (2023). Case report: Semaglutide-associated depression. Frontiers in Psychiatry.
- Mondin, T.C., et al. (2024). GLP-1 agonists can affect mood: A case of worsened depression associated with semaglutide. Case Reports.
- Chen, Y., et al. (2025). Association of semaglutide use with depressive symptoms and suicide attempt: case report and pharmacovigilance context. Journal of International Medical Research.
- Silverii, G.A., et al. (2024). Glucagon-like peptide-1 receptor agonists and mental health: A meta-analysis of randomized controlled trials. Diabetes, Obesity and Metabolism, 26(6), 2306-2313.
- Kalra, S., et al. (2022). Effect of antidepressants on glucagon-like peptide-1 receptor agonist–related outcomes. JAMA Network Open, 5(8), e2228225.
