Indexed on: 14 Sep '12Published on: 14 Sep '12Published in: CNS drugs
It is approximately 20 years since the serotonin (5-hydroxytryptamine; 5-HT) hypothesis of appetite control was formally stated. In that time, evidence has accumulated to confirm the role of serotonergic mechanisms in appetite control. At present, it is believed that serotonin 5-HT1B and 5-HT2C receptor subtypes mediate the capacity for an inhibition of food intake. Animal studies show that serotonin-induced suppression of eating generally preserves the behavioural satiety sequence, which is widely regarded as an indication of the operation of the natural physiological processes for meal termination and sustained post-meal satiety.The precise nature of the human serotonin feeding control system is less well understood. However, the 5-HT2C receptor has been implicated in human eating, although any role for the 5-HT1Dβ (h5-HT1B) receptor has yet to be determined. A consistent pattern of reduction in hunger motivation and energy intake is seen in human studies with a variety of serotonergic agents. With some drugs, but not all, a controlled restraint of appetite can be observed for at least 1 year. Patients receiving drugs report both a lower frequency and a reduced strength of urges to eat, together with the feeling of being more in control of their eating. Some serotonergic drugs, such as dexfenfluramine, can exert a continued suppression of appetite even following substantial bodyweight loss brought about by a period of following a very low calorie diet.Recent evidence has outlined the effects of diet composition on energy balance and bodyweight gain. This has generated interest in the effect of serotonergic drugs on preference for high fat diets and diets characterised by energy dense foods coupled with potent palatability, and carbohydrate craving. The experimental evidence is not unanimous on whether manipulation of serotonergic systems can selectively adjust macronutrient intake and food choice. Animal studies indicate that certain serotonergic drugs such as dexfenfluramine are potent inhibitors of the consumption of high fat diets. Human studies confirm that there is a suppression of the consumption of highly palatable high fat foods, and some studies indicate a possible selective avoidance of fat after the administration of dexfenfluramine and sumatriptan.Serotonergic drugs may be particularly helpful in curtailing episodes of over-consumption. However, it remains to be clearly demonstrated whether serotonin-based interventions are appropriate for the binge eating subpopulation of obese people and for those individuals displaying binge eating disorder.Despite the recent withdrawal from the market of appetite suppressants containing dexfenfluramine and fenfluramine, evidence suggests that serotonergic drugs can continue to play a useful role in the treatment of obesity. Their effects are achieved by adjusting biological mechanisms, which in turn reduce the impact of risk factors that facilitate the development of positive energy balance and bodyweight gain. Although the recent development of sibutramine as an appetite suppressant is encouraging, further research in this area is required to develop well tolerated and effective serotonergic appetite suppressants. Furthermore, an improvement in methodology in clinical research is required to enable detection of a selective modulation of high fat (high energy dense) foods.