Naltrexone prescription for weight loss is an increasingly discussed topic in UK clinical practice, particularly following the authorisation of the fixed-dose combination naltrexone/bupropion (Mysimba) by the MHRA. While naltrexone alone is not licensed as a standalone obesity treatment in the UK, the combination product offers a regulated, evidence-based option for eligible adults. This article explains how naltrexone is used for weight management, who may qualify under NHS or private pathways, what the prescribing process involves, and the key safety considerations patients and clinicians should be aware of before starting treatment.

How Naltrexone Is Used for Weight Loss in the UK

Naltrexone is used for weight loss in the UK only as part of the licensed combination product Mysimba (naltrexone/bupropion), which reduces appetite and food cravings by acting on hypothalamic POMC neurones and reward circuitry. Naltrexone alone is not licensed for this indication.

Naltrexone is an opioid receptor antagonist originally developed to support the management of alcohol and opioid dependence. In recent years it has attracted considerable interest as a component of weight management therapy. In the UK, naltrexone is not licensed as a standalone treatment for obesity, but it is available as part of a fixed-dose combination tablet — naltrexone/bupropion (brand name Mysimba) — which is authorised for use in the UK. The UK Summary of Product Characteristics (SmPC), available via the MHRA/Electronic Medicines Compendium (EMC), defines the licensed indication as the management of weight in adults with an initial body mass index (BMI) of 30 kg/m² or greater, or between 27 kg/m² and 30 kg/m² in the presence of at least one weight-related comorbidity such as type 2 diabetes, dyslipidaemia, or hypertension. The product was originally authorised via the European Medicines Agency (EMA) and its approval is reflected in the UK licence held by the MHRA.

The mechanism by which this combination supports weight loss involves two complementary pathways. Bupropion acts on dopamine and noradrenaline pathways in the hypothalamus to stimulate pro-opiomelanocortin (POMC) neurones, which reduce appetite.^[1][2] Naltrexone blocks opioid receptors — including those involved in the auto-inhibitory feedback on POMC neurones — and also acts on reward circuitry associated with food intake.^[1][2] Together, these actions are believed to reduce food cravings and promote satiety, helping patients adhere to a reduced-calorie diet.

It is important to note that naltrexone alone — at standard doses used for addiction — is not licensed for weight loss in the UK. Some clinicians may prescribe it off-label in low-dose formulations (so-called 'low-dose naltrexone'), but this use is unlicensed, the evidence base remains very limited, and it falls outside NICE-approved pathways. Low-dose naltrexone for weight management should not be used outside of specialist advice or a formal research setting. Any use of naltrexone for weight management should be discussed thoroughly with a qualified healthcare professional.

Key references: MHRA/EMC SmPC for Mysimba; EMA EPAR for Mysimba; NICE TA494.

Who May Be Eligible for a Naltrexone Prescription

Eligibility is guided by the UK SmPC (BMI ≥30 kg/m², or ≥27 kg/m² with a comorbidity) and NICE TA494, which restricts NHS prescribing to adults with a BMI ≥35 kg/m² plus a comorbidity within a specialist weight management service. Key contraindications include opioid use, uncontrolled hypertension, and a history of seizures.

Eligibility for a naltrexone-containing prescription for weight loss in the UK is guided by two distinct but related frameworks: the licensed indication set out in the UK SmPC, and the NHS commissioning criteria defined in NICE technology appraisal guidance TA494.

The UK SmPC licenses naltrexone/bupropion (Mysimba) for adults with a BMI of 30 kg/m² or above, or 27–29.9 kg/m² with at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity.

NICE TA494 sets more specific NHS commissioning criteria. The combination is recommended as an NHS option only when all of the following apply:

• BMI of 35 kg/m² or above with at least one weight-related comorbidity (such as type 2 diabetes, hypertension, or dyslipidaemia); or a BMI of 30–34.9 kg/m² where clinically indicated and agreed within a specialist service

• The individual has not responded adequately to dietary and lifestyle interventions alone

• Treatment is used alongside a reduced-calorie diet and increased physical activity

• Prescribing takes place within a specialist weight management service (tier 3 or above)

Local Integrated Care Boards (ICBs) and Health Boards may apply additional restrictions, so NHS availability can vary even where NICE criteria are met. The licensed indication is broader than NHS commissioning criteria; patients who do not meet TA494 thresholds may still be eligible for treatment via a private prescription following appropriate clinical assessment.

Contraindications and important cautions

Certain individuals are not suitable for this treatment. Contraindications listed in the UK SmPC include:

• Current or recent use of opioid medications, or opioid dependence (naltrexone will precipitate acute withdrawal)

• Uncontrolled hypertension

• Current or past history of seizures or conditions that lower the seizure threshold

• Eating disorders (bulimia nervosa or anorexia nervosa)

• Abrupt withdrawal from alcohol or benzodiazepines (risk of seizures)

• Use of monoamine oxidase inhibitors (MAOIs) within the preceding 14 days

• Severe hepatic impairment

• End-stage renal disease (ESRD)

• Pregnancy or breastfeeding

• Bipolar disorder or a history of mania (bupropion may precipitate manic episodes)

Additional cautions apply in older adults: the combination is generally not recommended in patients aged over 75 years due to limited data.^[1][2] Patients with a history of opioid dependence or those currently prescribed opioid-based pain relief (including codeine, tramadol, or dihydrocodeine) are excluded, as naltrexone will block the analgesic effect and may cause acute withdrawal. An opioid-free interval of at least 7–10 days is required before starting treatment; patients should be counselled that opioid sensitivity may increase after stopping naltrexone, raising the risk of overdose if opioids are subsequently taken.^[1][20]

A thorough medical history, medication review, blood pressure measurement, and assessment of renal and hepatic function are essential before any prescription is considered. Individuals who believe they may be eligible are encouraged to speak with their GP or a specialist obesity service in the first instance.

Key references: MHRA/EMC SmPC for Mysimba; NICE TA494; BNF monograph (naltrexone/bupropion).

How to Get a Prescription Through the NHS or Private Care

On the NHS, Mysimba must be initiated within a specialist (tier 3 or above) weight management service following GP referral, with availability varying by ICB. Private prescriptions are available from CQC-regulated clinics following a thorough clinical assessment.

Accessing a naltrexone prescription for weight loss in the UK typically involves either an NHS referral pathway or a private healthcare consultation.

NHS pathway

Under the NHS, NICE TA494 stipulates that Mysimba (naltrexone/bupropion) should only be initiated within a specialist weight management service (tier 3 or tier 4). A GP alone cannot initiate this treatment without an appropriate referral. Patients interested in this option should begin by speaking with their GP, who can assess eligibility and refer to a specialist service if appropriate.

NHS availability varies significantly by region. Some ICBs in England may not routinely commission Mysimba, meaning access can depend on local formulary decisions even where NICE criteria are met. Patients in Scotland, Wales, and Northern Ireland should check with their respective Health Boards, as prescribing policies differ across the devolved nations. NHS weight management service information is available via NHS England and the equivalent bodies in Scotland (NHS Scotland), Wales (NHS Wales), and Northern Ireland (Health and Social Care).

Private route

For those considering the private route, a number of registered clinics and online prescribing services offer consultations with qualified clinicians who can assess suitability and, where appropriate, issue a private prescription. It is essential that any private provider is regulated by the relevant UK healthcare regulator:

• England: Care Quality Commission (CQC)

• Scotland: Healthcare Improvement Scotland (HIS)

• Wales: Healthcare Inspectorate Wales (HIW)

• Northern Ireland: Regulation and Quality Improvement Authority (RQIA)

Prescribing clinicians should be registered with the General Medical Council (GMC) and must follow GMC Good practice in prescribing and managing medicines and devices standards. Patients should be cautious of unregulated online platforms offering naltrexone without a thorough medical assessment, ongoing monitoring, or clear follow-up arrangements.

Regardless of the route taken, a comprehensive consultation — including a review of current medications, medical history, blood pressure measurement, renal and hepatic function assessment, and discussion of realistic expectations — should always precede any prescription. Weight management medication is most effective when combined with structured lifestyle support, and regular follow-up must be arranged.

Key references: NICE TA494; CQC, HIS, HIW, RQIA regulatory guidance; GMC prescribing standards.

Dosage, Administration, and What to Expect

Mysimba is titrated over four weeks to a maximum of two tablets twice daily (32 mg naltrexone / 360 mg bupropion), taken whole with food. Treatment should be reviewed at 16 weeks and stopped if less than 5% body weight has been lost.

When prescribed as Mysimba, the standard dosing regimen follows a gradual titration schedule designed to minimise side effects, particularly nausea. The regimen set out in the UK SmPC is as follows:

• Week 1: One tablet (8 mg naltrexone / 90 mg bupropion) each morning

• Week 2: One tablet in the morning and one in the evening

• Week 3: Two tablets in the morning and one in the evening

• Week 4 onwards (maintenance): Two tablets in the morning and two in the evening (maximum daily dose of 32 mg naltrexone / 360 mg bupropion)

Tablets should be swallowed whole and not crushed, chewed, or divided, as this disrupts the extended-release formulation and may increase the risk of adverse effects. They should be taken with food to reduce gastrointestinal discomfort. Patients are advised to avoid taking tablets with a high-fat meal, as this can significantly increase drug absorption and the risk of adverse effects, as noted in the SmPC.^[1][3]

Special populations

Dose adjustments or additional caution are required in certain groups. The combination is not recommended in patients with end-stage renal disease or severe hepatic impairment. In moderate renal or hepatic impairment, the maximum dose may need to be reduced; prescribers should refer to the SmPC for specific guidance. The combination is generally not recommended in patients aged over 75 years due to limited clinical data in this group.^[1][2]

What to expect

Clinical trial data (the COR programme, referenced in the EMA EPAR for Mysimba) indicate that patients using naltrexone/bupropion alongside lifestyle intervention can achieve approximately 5–10% body weight reduction over 56 weeks, though individual results vary considerably.^[2][11] In accordance with NICE TA494 and the UK SmPC, treatment should be reviewed at 16 weeks: if a patient has not lost at least 5% of their initial body weight, the medication should be discontinued, as continued use is unlikely to be clinically beneficial.^[1][7]

Patients should be aware that weight loss is typically gradual and that the medication is intended to support, not replace, dietary changes and physical activity. Treatment should also be stopped if intolerable adverse effects occur or if blood pressure rises substantially during therapy. Regular follow-up appointments are important to monitor progress, blood pressure, and tolerability throughout the course of treatment.

Key references: MHRA/EMC SmPC for Mysimba; EMA EPAR for Mysimba (COR trial data); NICE TA494.

Possible Side Effects and Safety Considerations

The most common side effects are nausea, headache, insomnia, and raised blood pressure; serious risks include seizures, neuropsychiatric effects including suicidal ideation, and hypertensive crisis with MAOIs. Patients should seek urgent medical attention for seizures, chest pain, severe allergic reactions, or thoughts of self-harm.

As with all prescription medications, naltrexone/bupropion (Mysimba) carries a risk of side effects, and patients should be fully informed before starting treatment. The most commonly reported adverse effects include:

• Nausea (the most frequent complaint, particularly during the titration phase)

• Headache and dizziness

• Constipation or dry mouth

• Insomnia or sleep disturbance

• Increased heart rate or blood pressure

Nausea tends to improve as the body adjusts to the medication, and the gradual dose titration schedule is specifically designed to reduce this risk. Patients should be advised to persist through the initial weeks if side effects are mild and manageable, but to contact their prescriber if symptoms are severe or persistent.

Important safety warnings (per UK SmPC)

Seizures: Bupropion lowers the seizure threshold in a dose-dependent manner. The combination is contraindicated in individuals with a history of epilepsy or other conditions that increase seizure risk (including eating disorders, abrupt alcohol or benzodiazepine withdrawal, and concomitant use of medicines that lower the seizure threshold). If a seizure occurs during treatment, Mysimba must be stopped immediately and not restarted.

Neuropsychiatric effects: The UK SmPC includes warnings regarding neuropsychiatric effects, including changes in mood and behaviour. In rare cases, suicidal ideation and suicidal behaviour have been reported, particularly in younger patients.^[1][2] Patients and their carers should be advised to monitor for any changes in mood, unusual thoughts, or behaviour, and to seek prompt medical advice if these occur. Bupropion may also precipitate manic or hypomanic episodes in patients with bipolar disorder or a history of mania; this combination should be avoided in such patients.

Cardiovascular effects: Uncontrolled hypertension is a contraindication. In patients with controlled hypertension or established cardiovascular disease, treatment should be used with caution and blood pressure and heart rate monitored regularly. Treatment should be discontinued if a clinically significant and sustained increase in blood pressure or heart rate is observed.

Other cautions: Angle-closure glaucoma has been reported with bupropion; patients with raised intraocular pressure or at risk of acute angle-closure glaucoma should be monitored.^[1][17] Patients with type 2 diabetes treated with insulin or oral hypoglycaemic agents may be at increased risk of hypoglycaemia during weight loss; blood glucose monitoring and medication adjustment may be required. Dizziness is a recognised adverse effect; patients should be advised to exercise caution when driving or operating machinery until they know how the medication affects them.

Drug interactions

Naltrexone/bupropion has several clinically significant interactions. Bupropion is a strong inhibitor of CYP2D6 and can substantially increase plasma concentrations of drugs metabolised by this enzyme, including certain antidepressants (SSRIs, tricyclics), antipsychotics, beta-blockers (e.^[1][9]g. metoprolol), and tamoxifen. MAOIs are contraindicated within 14 days of starting or stopping Mysimba due to the risk of hypertensive crisis.^[1][5] Concomitant use with opioid analgesics (including codeine, tramadol, and dihydrocodeine) is contraindicated, as naltrexone will block their effect and may precipitate withdrawal. Patients should always inform their prescriber and pharmacist of all medications — including over-the-counter medicines and herbal products — before starting treatment.

When to seek urgent medical help

Patients should seek urgent medical attention (call 999 or go to A&E) if they experience:

• A seizure or convulsion

• Signs of a severe allergic reaction (swelling of the face, lips, tongue, or throat; difficulty breathing; severe rash)

• Chest pain or palpitations

• Severe or sudden headache with confusion or visual disturbance

• Thoughts of self-harm or suicide

Reporting side effects

Patients and carers are encouraged to report any suspected side effects directly to the MHRA via the Yellow Card scheme at www.mhra.gov.uk/yellowcard or via the Yellow Card app. Reporting helps the MHRA monitor the ongoing safety of medicines in the UK.

Key references: MHRA/EMC SmPC for Mysimba; BNF monograph (naltrexone/bupropion); MHRA Yellow Card scheme.

Frequently Asked Questions