Clinical Medicine Reviews in Therapeutics

The serotonin (5-HT) system is implicated in the control of human appetite expression. However, previous serotonergic approaches to obesity, d-fenfluramine and sibutramine, were withdrawn over issues of safety. Selectively targeting hypothalamic 5-HT2C receptors should reduce the side effects produced by previous treatment. Lorcaserin is the first of a new generation of highly selective 5-HT2C agonists to pass through clinical development. Data is limited but the drug produces significant reductions in energy intake. These appear small compared to those reportedly produced by sibutramine and there is little evidence to indicate behavioural specificity or a clear satiety effect. However, Lorcaserin produces significant placebo-subtracted weight loss over two years of treatment which may be greater than current treatments such as the lipase inhibitor orlistat. Drugs that strengthen satiety may help individuals resist the urge to over-consume and maintain the reduction in energy intake required for successful weight control. However, for a number of patients Lorcaserin proved to be ineffective. For a centrally acting agent the drug's effect on appetite and behaviour remain poorly characterised. In summary, Lorcaserin produces statistically significant effects on energy intake, but the clinical significance of these findings is still debatable. Furthermore, the history of serotonin drugs indicates caution is warranted.