What is amitriptyline?
Amitriptyline is a tricyclic antidepressant that’s been used in the UK since the 1960s. It works by increasing the levels of serotonin and noradrenaline in the brain, which can help improve mood and reduce pain signals.
It’s prescribed for several different conditions. According to its UK SmPC, amitriptyline is licensed for major depressive disorder, neuropathic pain, chronic tension-type headache prevention, and migraine prevention.1
It’s also commonly used off-licence for fibromyalgia and other chronic pain conditions. The dose varies depending on the condition being treated, with lower doses (10-25 mg) typically used for pain and higher doses (75-150 mg) for depression.
What is Mounjaro?
Mounjaro is a weight-loss injection that mimics two gut hormones, GLP-1 and GIP, which help us feel full and manage blood sugar levels after eating.
The drug in Mounjaro is tirzepatide. It’s a long-acting medication injected once a week, and it takes 4-5 weeks to reach a steady level in the body where its effects become more consistent.
Research suggests Mounjaro supports weight loss of up to 26% after two years, which is around 10% more weight loss than another well-known weight-loss injection, Wegovy.2
Potential interactions to be aware of
No clinical trials have specifically studied Mounjaro alongside amitriptyline. The interactions below are based on what we know about each medication individually, so they remain theoretical rather than confirmed.
Heart rate
Both Mounjaro and amitriptyline can increase heart rate through different mechanisms. Amitriptyline raises heart rate through its anticholinergic effects, which reduce the body’s natural ‘braking system’ on the heart. Tachycardia (a fast heart rate) is listed as a very common side effect in its SmPC.1
Tirzepatide also modestly increases heart rate. Data from the SURMOUNT-1 trial showed increases of around 2-3 beats per minute compared to placebo after 72 weeks.3
When taken together, there’s a theoretical risk that these effects could add up. In practice, for most people the increase from Mounjaro is small. But if you notice a resting heart rate consistently above 100 beats per minute, chest discomfort, or unexplained palpitations, contact your GP.
Gastric emptying and absorption
Mounjaro slows gastric emptying (how quickly food and medications move from the stomach into the intestine). This is one of the main ways it reduces appetite.
Amitriptyline also has anticholinergic properties that can slow the digestive system, with constipation listed as a very common side effect.1 When taken together, these effects could theoretically overlap.
The clinical significance isn’t known. Slower gastric emptying could affect how quickly amitriptyline is absorbed, though it shouldn’t change the total amount absorbed. If you notice worsening constipation or nausea after starting both medications, let your GP know.
Blood sugar
Mounjaro helps lower blood sugar levels, which is beneficial for people with type 2 diabetes or insulin resistance. Amitriptyline can also affect blood sugar, with its SmPC noting it may modify insulin and glucose responses.1
For most people without diabetes, this is unlikely to cause problems. If you have diabetes and take both medications, your healthcare team may want to monitor your blood sugar more frequently.
How Mounjaro and amitriptyline compare on shared pathways
| Effect |
Mounjaro (tirzepatide) |
Amitriptyline |
Combined consideration |
| Heart rate |
Modest increase of 2-3 bpm (SURMOUNT-1)3 |
Increase via anticholinergic and noradrenaline reuptake effects1 |
Possible additive effect; monitor resting heart rate |
| Gastric emptying |
Slows gastric emptying (primary mechanism of appetite reduction) |
Anticholinergic effects can slow gut motility1 |
Theoretical overlap; watch for worsening constipation or nausea |
| Blood sugar |
Lowers blood sugar levels |
May modify insulin and glucose responses1 |
Relevant mainly for people with diabetes; monitor if applicable |
| Weight |
Up to 26% weight loss after two years2 |
Weight gain is a recognised side effect1 |
Mounjaro may offset amitriptyline-related weight gain |
| Nausea |
Common side effect, especially during dose escalation |
Listed as a very common side effect1 |
Both can cause nausea; report persistent symptoms to your GP |
Common questions answered
Can Mounjaro help with weight gain caused by amitriptyline?
Weight gain is a recognised side effect of amitriptyline. Research shows that people living with obesity have a 55% higher risk of developing depression, while people with depression have a 58% higher risk of developing obesity.4
Mounjaro’s weight-loss effects could help counteract amitriptyline-related weight gain, potentially benefiting both your physical and mental health. Data from the SURMOUNT-1 trial also showed that participants taking tirzepatide experienced improvements in quality of life and psychosocial function compared to placebo.5
Should I separate the timing of taking these medications?
There’s no specific guidance recommending this. Mounjaro’s effects on gastric emptying last throughout the week, not just after injection. Continue taking amitriptyline at your usual time, whether that’s morning or evening.
Will Mounjaro affect how well my amitriptyline works?
Slower gastric emptying from Mounjaro could theoretically delay how quickly amitriptyline is absorbed, but it shouldn’t reduce the total amount your body absorbs. If you notice any changes in your symptoms after starting Mounjaro, speak to your GP.
What warning signs should I watch for?
Contact your healthcare team if you experience a resting heart rate consistently above 100 beats per minute, unexplained palpitations or chest discomfort, severe or persistent constipation, persistent nausea that doesn’t improve, or significant changes in your mood or pain levels.
I’m taking amitriptyline for pain, not depression. Does that change things?
The interaction considerations are the same regardless of why you’re taking amitriptyline. The heart rate, gastric motility, and blood sugar effects relate to how the drug works in your body, not the condition it’s treating. Lower doses used for pain (10-25 mg) may carry a smaller risk of interaction than higher doses used for depression.
Can I stop taking amitriptyline now that I’m losing weight on Mounjaro?
Never stop amitriptyline without speaking to your GP first. Suddenly stopping can cause withdrawal symptoms including nausea, headache, and sleep disturbance. If you and your GP decide it’s appropriate, the dose should be reduced gradually over several weeks.
Managing multiple medications can feel stressful. What should I do?
It’s completely normal to feel uncertain when taking more than one medication. The most practical step is to keep your GP informed about everything you’re taking. They can review your medications together and monitor for any issues. If you’re feeling anxious about it, that’s worth mentioning too.
Are there people who shouldn’t take this combination?
People with existing heart rhythm problems, severe gastroparesis (very slow stomach emptying), or those taking other medications that affect heart rate should be assessed more carefully. Your prescriber will review your full medication list and medical history before approving this combination.
Take home message
You can take Mounjaro alongside amitriptyline. There are no direct contraindications between the two medications.
The main considerations are a theoretical overlap in heart rate effects and gastric motility, but for most people these aren’t clinically significant. Let your GP know you’re taking both so they can monitor you appropriately.
Mounjaro may also help offset weight gain associated with amitriptyline, which could benefit both your physical health and the conditions amitriptyline is treating.
Second Nature’s Mounjaro programme
Second Nature combines Mounjaro with a structured habit-change programme built around a balanced plate approach (half vegetables, quarter protein, quarter complex carbohydrates, plus a serving of fat) and support from registered dietitians and health coaches.
A 2025 study published in JMIR Formative Research found that active subscribers on Second Nature’s semaglutide-supported programme achieved an average weight loss of 19.1% at 12 months, with 77.7% achieving at least 10% weight loss.6
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). Amitriptyline 10 mg Film-Coated Tablets – Summary of Product Characteristics
- Wadden, T.A. et al. (2023). Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. JAMA, 330(23), 2258-2269.
- 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.
- Poon, J.L. et al. (2023). Improved mental and psychosocial patient-reported outcomes among people with obesity treated with tirzepatide: results from the SURMOUNT-1 study. Journal of the Endocrine Society, 7(Supplement 1).
- Richards, R. et al. (2025). Real-world outcomes of a digital health programme combining GLP-1 receptor agonist therapy with behavioural support. JMIR Formative Research, 9(1), e72577.
