Naltrexone / bupropion in obesity

The synergistic activity of the bupropion/naltrexone combination was based on an understanding of the physiological responses to the neural circuitry affected by each drug, unlike most other obesity medications which were developed following observations of weight loss during therapeutic intervention

• bupropion is a monoamine reuptake inhibitor that increases the synaptic activity of dopamine and norepinephrine
  • bupropion also stimulates the hypothalamic pro-opiomelanocortin (POMC) neurons to decrease appetite and increase energy expenditure
    • POMC is cleaved into alpha-melanocyte-stimulating hormone (alpha-MSH) and beta endorphin to activate neural pathways with opposing effects on appetite
• naltrexone, an opioid antagonist, blocks the orexigenic effects of P-endorphin activity, which in theory should enhance the hypophagic effect of alpha-MSH

NICE no longer recommends naltrexone–bupropion within its marketing authorisation for managing overweight and obesity in adults alongside a reduced-calorie diet and increased physical activity.

NICE state: Clinical trial evidence shows that naltrexone–bupropion with lifestyle measures is more effective than lifestyle measures alone, but its long-term effectiveness is unknown. The estimate of cost effectiveness for naltrexone–bupropion with lifestyle measures, compared with lifestyle measures alone, is highly uncertain because of uncertainties in the modelling assumptions. Large numbers of people could be eligible for treatment which could potentially be long-term, leading to high overall costs for naltrexone–bupropion. Therefore, in these circumstances more certainty is needed that naltrexone–bupropion will provide value for the NHS.

Reference

1. NICE. Naltrexone–bupropion for managing overweight and obesity. Technology appraisal guidance TA494. Published: December 2017