Jump to: What does UK prescribing guidance say? | Are there any indirect effects to be aware of? | Can Mounjaro affect your mood? | Practical tips for taking both medications | Frequently asked questions | Take home message
You can take Mounjaro (tirzepatide) with sertraline. The UK Summary of Product Characteristics (SmPC) for Mounjaro and the British National Formulary (BNF) list no interactions between tirzepatide and antidepressants, including SSRIs like sertraline.1
The reason there’s no interaction comes down to how each drug is processed by your body. Mounjaro is broken down through a process called proteolytic cleavage, 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 Mounjaro while already on sertraline. This typically settles as your body adjusts.
If you’re considering Mounjaro 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: Mounjaro (tirzepatide) is a prescription-only medication for treating type 2 diabetes and managing obesity. 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 Mounjaro and sertraline?
The official UK prescribing information for Mounjaro doesn’t list any clinically relevant interactions with antidepressant medications.1
This is largely because of how differently these medications work in your body:
- Mounjaro is a peptide-based medication that mimics two gut hormones (GLP-1 and GIP). 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 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 Mounjaro SmPC does note that tirzepatide 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 could cause problems) or those requiring 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 Mounjaro 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 |
Mounjaro |
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 Mounjaro or when your dose increases.
The good news is that Mounjaro’s gastrointestinal side effects typically improve over time. In 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 Mounjaro 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
The SURMOUNT trials (the main clinical trials for Mounjaro in obesity) also showed improvements in mental health and psychosocial quality-of-life measures. In SURMOUNT-1, all doses of tirzepatide showed significant improvements in mental health scores compared to placebo.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
- Improved physical function and mobility
- Healthier eating habits developed while on the medication
Evidence suggesting caution is needed
However, a 2024 cohort study of over 162,000 patients found an association between GLP-1 medication use and increased rates of depression and anxiety diagnoses.6
A large meta-analysis of randomised controlled trials published in 2024 found no significant association between GLP-1 medications and psychiatric disorders overall, but the authors noted that ongoing monitoring is advisable.7
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 Mounjaro 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 Mounjaro, here are some practical suggestions.
Timing your medications
There’s no specific requirement to take Mounjaro and sertraline at different times. Mounjaro 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 Mounjaro:
- 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 Mounjaro 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 Mounjaro make my sertraline less effective?
No. There’s no evidence that Mounjaro affects how well sertraline works. While Mounjaro does slow gastric emptying, this doesn’t significantly impact sertraline absorption or effectiveness.1
Should I take Mounjaro and sertraline at different times of day?
There’s no requirement to separate them. Mounjaro is a weekly injection, and sertraline is typically taken daily. You can continue your usual sertraline schedule without adjusting for Mounjaro.
What if my nausea gets worse when I start Mounjaro?
Some increased nausea is common when starting Mounjaro 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. The SURMOUNT trials showed improvements in mental health quality of life scores with tirzepatide treatment.5 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 interactions with Mounjaro.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 Mounjaro?
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 Mounjaro?
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 Mounjaro alongside sertraline. UK prescribing guidance confirms no clinically relevant drug interactions between tirzepatide 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 Mounjaro. These typically improve with time.
While research on GLP-1 medications and mental health is ongoing, the current evidence doesn’t suggest avoiding Mounjaro 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 Mounjaro 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.
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References
- Electronic Medicines Compendium. (2024). Mounjaro KwikPen Summary of Product Characteristics (SmPC).
- Jastreboff, A.M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387(3), 205-216.
- 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.
- Murphy, M., et al. (2023). Improved Mental And Psychosocial Patient-Reported Outcomes Among People With Obesity Treated With Tirzepatide: Results From SURMOUNT-1 Study. Journal of the Endocrine Society, 7(Suppl 1).
- Kornelius, E., et al. (2024). The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy. Scientific Reports, 14, 24433.
- 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.
