The concomitant use of sibutramine and monoamine oxidase inhibitors can increase the risk of serotonin syndrome.
Many who are overweight or obese struggle with the condition and attempt to find a reason for their present condition but, except in very rare cases, it is not a genetic or metabolic problem. Obesity results from the consumption of significantly more calories than the body needs to get through the day. The body has a mechanism for turning any unneeded calories into fat and stores that fat for later when it might be needed. However, when large amounts of calories continue to be consumed, the stored fat is never needed and more fat is added to it aggravating the condition. The opposite of course is also true, there is no miracle to losing those pounds, fewer calories must be consumed than the body needs so that it burns that stored fat and eliminates it.
Normally, 6 months after the initiation of sibutramine treatment food intake recovers and body weight plateaus until sibutramine is discontinued [1 ]. This phenomenon is called sibutramine tachyphylaxis. Upon discontinuation, regain of the lost weight is frequently observed. This highlights that sibutramine is effective at reducing body weight and food intake when given for short periods of time (6-12 months), but its effectiveness diminishes when administered chronically (> 1 year) [18 ]. Indeed, in humans there are no studies longer than 2 years evaluating the weight reducing effects of sibutramine [2 ]. Sibutramine tachyphylaxis may be explained by homeostatic counterregulatory mechanisms that promote resistance to further weight reduction actions of this drug [4 ]. These counterregulatory mechanisms can be explained as follow. Short-term administration of sibutramine lowers the body weight set point. This body weight set point is not permanently reduced by long-term administration of sibutramine, since the brain will oppose this change by stimulating appetite [8 ], food reward (pleasure associated with consumption of a palatable food) [10 , 18 ] and food intake, and also by decreasing basal energy expenditure and dampening reductions in body fat stores. Boozer et al. [19 ] points out that the decreased circulating levels of leptin in blood accompanying body fat reduction may trigger counter regulatory mechanisms that block further weight loss effects of sibutramine, as they found out that restoration of circulating levels of leptin during long-term (8-weeks) sibutramine therapy decreased body weight and food intake and increased fat oxidation in obese rats [8 ].