naltrexone / bupropion in obesity

Last edited 08/2019 and last reviewed 02/2022

  • 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

  • naltrexone/bupropion ER is a well-tolerated safe medication for the long-term management of obesity (2)
    • in the large-scale randomized noninferiority cardiovascular outcomes trial that was prematurely discontinued, naltrexone/ bupropion ER resulted in 2.5% (placebo-subtracted) weight loss at 104 weeks (n = 2408 naltrexone/bupropion-treated subjects, n = 2264 placebo-treated subjects) (3)
      • despite the large-scale efforts of the randomized noninferiority cardiovascular outcomes trial, the FDA requirement for cardiovascular safety still has not been met (2)

  • concern about bupropion/naltrexone and driving ability (4)
    • in the UK, there has been guidance to "Advise patients that naltrexone/bupropion has been associated with adverse reactions such as dizziness or somnolence, which can affect ability to drive, operate machinery, or perform dangerous tasks. Advise patients not to drive if they suspect their ability may be impaired. .."

    • Advice for healthcare professionals:
      • people taking naltrexone/bupropion may commonly experience dizziness or somnolence, and may rarely experience loss of consciousness or seizure
      • these effects would pose a risk to their ability to drive or operate machinery especially at the beginning of the treatment or during the dose titration phase
      • advise patients experiencing adverse reactions with naltrexone/bupropion to not drive or operate machinery until they have resolved

Reference:

Related pages:

naltrexone (Nalorex)

bupropion