Mysimba

Mysimba is an oral medication for weight reduction that combines two active ingredients: naltrexone (an opioid antagonist) and bupropion (an antidepressant/smoking cessation aid).

Unlike the GLP-1 agonists (Wegovy, Ozempic), Mysimba acts primarily in the brain, on the reward and satiety center. It is taken as a tablet, not injected.

Mysimba is approved for adults with a BMI ≥ 30 or a BMI ≥ 27 with comorbidities.

The combination acts synergistically on the brain:

Bupropion:

• Inhibits the reuptake of dopamine and norepinephrine
• Stimulates neurons in the hypothalamus that regulate appetite
• Reduces the craving for food

Naltrexone:

• Blocks opioid receptors
• Enhances and prolongs the effect of bupropion
• Reduces the feeling of reward from eating

Together:

• Decreased appetite
• Reduced craving for food (especially "emotional eating")
• Increased energy expenditure

Mysimba is suitable for:

• Adults with a BMI ≥ 30 (obesity)
• Adults with a BMI ≥ 27 and at least one weight-related comorbidity
• In each case as an adjunct to a reduced-calorie diet and increased physical activity
• As an alternative to injectable medications

Not suitable in cases of uncontrolled high blood pressure, epilepsy, eating disorders.

Gradual dose escalation:

• Week 1: 1 tablet in the morning
• Week 2: 1 tablet in the morning + 1 in the evening
• Week 3: 2 tablets in the morning + 1 in the evening
• From week 4: 2 tablets in the morning + 2 in the evening (maintenance dose)

Maximum dose: 4 tablets daily (2-0-2)

• Swallow the tablets whole, without chewing, with water
• Preferably with meals
• Not with a high-fat meal (increases the risk of seizures)
• Follow the dose escalation as prescribed

Absolute contraindications:

• Uncontrolled high blood pressure
• Epilepsy or a history of seizures
• Tumor of the central nervous system
• Alcohol or benzodiazepine withdrawal
• Bulimia or anorexia
• Concurrent use of MAO inhibitors
• Opioid use or opioid withdrawal
• Severe hepatic insufficiency
• Bipolar disorder (including a past history)
• End-stage renal insufficiency

Relative contraindications:

• Severe depression
• Moderate or severe renal impairment (no more than 2 tablets daily)

Very common:

• Nausea
• Constipation
• Headache
• Vomiting

Common:

• Dizziness
• Dry mouth
• Sleep disturbances
• Anxiety, irritability
• Increase in blood pressure
• Abdominal pain

Rare but serious:

• Seizures (risk increased with rapid dose escalation)

Frequency not known, but serious:

• Suicidal thoughts (monitor in patients with a psychiatric history)

Contraindicated:

• MAO inhibitors (14-day interval)
• Opioids (naltrexone blocks their effect!)
• Other bupropion products

Caution:

• Medications that raise blood pressure
• Medications that lower the seizure threshold
• CYP2D6 substrates (tamoxifen, metoprolol)