My enthusiasm for cue exposure therapy as an intervention has been weakened by my review of the literature. That doesn’t mean that cues are not real, cravings are not a serious problem, and resisting cravings is not a part of the treatment of addiction (including food addiction). For me, it mainly means that a Pavlovian external-based process is unlikely to be all that effective at altering the core neurobiological problem. I do have some hope for the impact of increased frontal control through CBT, yet, there, too, I still have doubts.
Several talks have looked at the value of the combination of naltrexone and bupropion for obesity treatment and there is an FDA-approved weight-loss product on the market with this combination. The data shows that this combination has about the same effect as most pharmacological interventions (5-9% of weight loss). But that may be because cravings are not a problem for every single obese patient. One of the mistakes in today’s research is that we throw every patient into the same bucket and then give them the same intervention. This goes against the whole concept of personalized medicine. If we really want to see what the effects of drugs are we need to select the population that is most likely to respond to the drug and then do a trial with just those people.
Naltrexone/buproprion is probably the best choice for someone with cravings since it targets the problems like cravings for sugary food and difficulty resisting cravings. Two articles looked into the use of these medications in obesity treatment.
- Caixàs Assumpta, Albert Lara, Capel Ismael, Rigla Mercedes. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. Drug Des Devel Ther. September 18, 2014;8:1419-1427. doi:10.2147/DDDT.S55587.
Appetitive traits were assessed using self-report measures in these trials. In COR-I bupropion/naltrexone produced improvements on selected items in the Control of Eating Questionnaire (COEQ), namely increased fullness, reduced hunger (satiety effects), reduced desire for sweet, non-sweet or starchy foods (reward effects), increased ability to control eating and resist food cravings (craving control). Similarly naltrexone/bupropion-treated patients in COR-II report increased ability to resist cravings and control eating, as well as reduced frequency of food craving (as measured by COEQ) again suggesting effects on reward and control (if not satiety) at week 56.
- Roberts Carl A, Christiansen Paul, Halford Jason CG. Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?. Acta Diabetol. 2017;54(8):715-725. doi:10.1007/s00592-017-0994-x.
“Contrave” is a fixed-dose combination of naltrexone and bupropion. The idea of associating an antagonist of the opioid receptors, in order to block the autoinhibitory feedback, arises as a good way to enhance the anorexigenic effect of bupropion. The effect of the combination is synergistic, and the results are at least fully additive in all electrophysiological studies Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved in self-control and internal awareness might underlie its therapeutic benefits in obesity.
Another article delved into the neurobiology of how combined Naltrexone/buproprion affected the brain’s functional connectivity.
- Wang Gene-Jack, Zhao Jizheng, Tomasi Dardo, et al. Effect of combined naltrexone and bupropion therapy on the brain’s functional connectivity. Int J Obes (Lond). 2018;42(11):1890-1899. doi:10.1038/s41366-018-0040-2.
Results: After combination of sustained release (SR) naltrexone and SR bupropion (NB32) treatment, the group showed lower local and global functional connectivity density (FCD) than the placebo group in the right superior parietal cortex and lower local FCD in the left middle frontal gyrus. Seed-voxel correlation analysis for the right superior parietal cortex seed demonstrated higher positive FC with the dorsal anterior cingulate gyrus (ACC), bilateral insula, and left superior parietal gyrus and stronger negative FC with right inferior frontal gyrus and right superior parietal cortices for the NB32 than the placebo group. Further, the NB32 group showed a significant correlation between local FCD change after treatment in left middle frontal gyrus and craving control scores (r = 0.519, p = 0.039).
Conclusions: NB32 treatment decreased local and global FCD in superior parietal cortex and increased its connectivity with ACC (involved with saliency attribution), insula (interoception), and decreased local FCD in the medial prefrontal cortex (craving), which might underlie NB32 improved control over eating behaviors.
And this article provides a nice follow up on my comment about tailoring.
- Roberts Carl A, Christiansen Paul, Halford Jason CG. Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?. Acta Diabetol. 2017;54(8):715-725. doi:10.1007/s00592-017-0994-x.
In the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options.
Perhaps pharmacotherapy can work for some people, but with only 5-9% weight loss and most of the weight being regained when the medication is stopped, it’s not a solution for the whole problem of obesity, and it’s not necessarily a solution for all. Personalized medicine and tailored treatment can help address the obesity problem. Pharma is not always the solution.
