Phentermine-lorcaserin combo enhances reduction in food cravings
The addition of the appetite suppressant phentermine to the 5-HT2C* receptor agonist lorcaserin improves control of food cravings among individuals who are under a short-term energy-restricted diet, a new study shows.
A total of 235 nondiabetic obese or overweight patients were randomized 1:1:1 to receive twice-daily lorcaserin hydrochloride 10 mg either alone or in combination with once- (LP1) or twice-daily phentermine 15 mg (LP2). Food cravings were evaluated using the Food Craving Inventory (FCI) and Control of Eating Questionnaire (COEQ) over a 12-week period. Participants were instructed to engage in a daily 30-minute moderate-intensity exercise programme and to reduce caloric intake to 600 kcal below their estimated daily requirement. [Obesity 2018;26:332-339]
Compared with lorcaserin alone, there was greater reduction in total FCI score among LP2 recipients at week 12 (least squares [LS] mean change, -0.84 vs -0.65).
COEQ assessment also revealed significantly reduced scores at week 12 in the LP2 vs the lorcaserin alone arms in terms of hunger (LS mean change, -11.0; p=0.002), difficulty in resisting food cravings (LS mean change, -12.6; p=0.001), eating in response to cravings (LS mean change, -12.5; p=0.001), and difficulty in controlling eating (LS mean change, -16.1; p<0.001).
With regards to craving assessment for specific foods, significant reductions at week 12 were observed for chocolate (LS mean change, -11.3; p=0.005), other sweets (LS mean change, -13.7; p=0.001), and starchy foods (LS mean change, -8.1; p=0.030).
Aside from its proven efficacy against nicotine-seeking and impulsive behaviours, [ACS Chem Neurosci 2015;6:1231-1240; Behav Pharmacol 2014;25:775-783; Neuropsychopharmacology 2012;37:1177-1191] lorcaserin has also been found to provide benefit for craving-triggered eating disorders such as emotional and binge eating. [Int J Eat Disord 1998;23:353-360; Diabetes 2016;65:2943-2953]
Phentermine has been shown to reduce body weight and cravings when used in conjunction with a meal replacement system and nutritional counselling, [Obesity (Silver Spring) 2016;24:2344-2350] and when compared against naltrexone and bupropion. [Obesity (Silver Spring) 2013;21:935-943] However, further trials are warranted to validate this comparison, noted the researchers.
The favourable neurobiological and behavioural responses associated with lorcaserin and phentermine appear to validate the influence of anti-obesity medications on the motivational drive to eat or reward-induced eating, said the researchers.
“[However,] if food cravings were psychological manifestations of energy depletion reflected as a metabolic need and expressed as hunger, the reduction in energy intake during the treatment period would be expected to increase food cravings,” the researchers pointed out. “[Nonetheless, our findings suggest] that lorcaserin in combination with phentermine can enhance the reduction in food cravings [despite] energy restriction.”
Apart from hunger, food cravings may also be triggered by a multitude of biologic, emotional, and cognitive processes such as menstrual-related changes, dysphoric mood states, and expectations and cognitions. [J Affect Disord 1995;34:157-164; Appetite 1991;17:187-197]
“Eating in the absence of nutritional need is evidence of a strong and overpowering control exerted by the corticolimbic structures,” the researchers pointed out. Most people would rather give in than restrain themselves from their cravings, using this to validate their food consumption. [Proc Nutr Soc 2007;66:277-285] This, in turn, could lead to overeating and, eventually, overweight and obesity. [Appetite 1990;15:231-246]
These factors highlight the importance of interventional measures that can suppress cravings and subsequently help affected individuals fight their battle against overeating, underscored the researchers, who called for further trials to determine the ability of the lorcaserin-phentermine combo to address physiologic hunger and reward mechanisms, its long-term effects, and patients who would most benefit from this approach.