Contrave

Antidepressant (bupropion, atypical), Opioid antagonist (naltrexone), Anorectic (weight-loss agent), Fixed-dose combination

Bupropion / Naltrexone

Contrave (US), Mysimba (EU)

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Titration strategies

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Effects

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Summary

Classes

Antidepressant (bupropion, atypical), Opioid antagonist (naltrexone), Anorectic (weight-loss agent), Fixed-dose combination

Common uses

Chronic weight management adjunct in obesity (BMI ≥30, or ≥27 with risk factors)▲0▼

Pharmacy

Starting dose

Week 1: 1 tablet (8/90 mg) PO morning; week 2: 1 tablet AM + 1 PM; week 3: 2 AM + 1 PM; week 4 onward: 2 AM + 2 PM (32 mg naltrexone / 360 mg bupropion/d)

Preparations

8 mg naltrexone / 90 mg bupropion ER tablets (titration-pack design)

US FDA Max

32 mg naltrexone / 360 mg bupropion per day

Pharmacology

Routes

Oral

Onset

Modest appetite suppression within weeks; weight loss over months

Duration

12 hours (BID dosing required)

Half-life

Naltrexone ~4 hours (6β-naltrexol metabolite ~13 hours); bupropion ~21 hours

Bioavailability

Naltrexone ~5% (oral, extensive first-pass to 6β-naltrexol); bupropion ER ~87%

Pregnancy

Contraindicated in pregnancy (FDA label).^{[citation needed]}

Legal status

Rx-only in US. Contraindicated in uncontrolled hypertension, seizure disorder, anorexia/bulimia, chronic opioid use (would precipitate withdrawal), and during/within 14 days of MAOI use. Carries Boxed Warning for suicidal thoughts and neuropsychiatric reactions (bupropion class effect)

Purported mechanism

Bupropion inhibits norepinephrine and dopamine reuptake, activating POMC neurons in the hypothalamus to release α-MSH (suppressing appetite) and β-endorphin (which would normally feed back to inhibit POMC). Naltrexone blocks the β-endorphin autoinhibition, sustaining the appetite-suppressing POMC activity. The combination achieves greater weight loss than either component alone.▲0▼ Modest absolute weight loss (~5% from baseline at 1 year) versus placebo. Interaction profile includes CYP2D6 inhibition (bupropion), so dose-adjustment for tricyclic antidepressants, β-blockers metabolized by 2D6, and certain neuroleptics is warranted.