Sibutramine is an amphetamine derivative and serves as an appetite suppressant in its capacity as an indirect stimulator of the sympathetic nervous system. The active ingredient belongs to the group of serotonin–norepinephrine reuptake inhibitors and thus comes close in its mode of action to various antidepressants and the ADHD drug methylphenidate. Drugs containing sibutramine were withdrawn from the market in European countries in 2010 on the recommendation of the European Medicines Agency because of significant side effects.
What is sibutramine?
Sibutramine belongs to the appetite suppressant group of drugs and has been used for the treatment of severe obesity (overweight). The drug sibutramine, an amphetamine derivative that belongs to the appetite suppressant (anorectic) drug group, was used for the treatment of severe overweight (obesity) until it lost its approval in 2010. The appetite-suppressing property of sibutramine is mainly due to its action as a serotonin–norepinephrine reuptake inhibitor (SNRI). This results in an increase in the concentration of the neurotransmitter serotonin and the stress hormone adrenaline in the extracellular space and in the synaptic cleft of the nerves involved, which is equivalent to indirect stimulation of the sympathetic nervous system. In the event of danger or other stressor, the sympathetic nervous system normally ensures that stress hormones are released and the body’s metabolism is set to call up short-term mental and physical peak performance for flight or attack. In the course of the short-term metabolic changes, appetite suppression also occurs, among other things. Due to a large number of harmful side effects, some of which were life-threatening, the European Medicines Agency recommended in January 2010 that drugs containing sibutramine no longer be approved for treatment. This recommendation has since been endorsed by industrialized nations, which have withdrawn approval for sibutramine-containing drugs such as Reductil, Meridia, and LiDa.
Pharmacologic effect
The variety of effects that sibutramine has on various tissues, organs, and the CNS, in addition to appetite inhibition, can be largely explained by its indirect stimulation of adrenergic receptors (adrenoceptors). As a result of the reuptake inhibition of the neurotransmitters serotonin and norepinephrine, the increased extracellular concentration of the neurotransmitters leads to a correspondingly increased occupation and stimulation of the receptors. The adrenoceptors thus stimulated trigger metabolic processes similar to those of “real” sympathetic excitation. This means that all tissues and organs innervated by sympathetic nerves and presenting adrenoceptors are affected. This also applies to the CNS and platelets, which also carry adrenoceptors on their surface. The effects on the psyche can usually be described as euphoric and are similar to those of certain psychotropic drugs. The overall pharmacological effect of sibutramine can be described as sympathomimetic. In addition to other undesirable side effects, it was primarily the effects on the cardiovascular system, such as cardiac arrhythmias and hypertension, as well as the strong influence on the psyche, that led to the withdrawal of approval for sibutramine-containing drugs in 2010.
Medical application and use
The period during which the drug sibutramine had a marketing authorization in Germany and other European countries covers about 12 years, from 1999 to 2010. Only in Italy, after the occurrence of two deaths, the drug was officially withdrawn from the market as early as 2002. The use of drugs containing sibutramine was subject to strict rules. The drug was to be prescribed exclusively for the supportive treatment of obesity with a body mass index (BMI) of 30 or more. Supportive in this case meant that a proven diet should be followed at the same time as a specific exercise program. In addition, the rule was that obesity treatment with sibutramine should be discontinued if at least a 5% weight loss was not achieved after a treatment period of 3 months. The obesity to be treated could be genetic or acquired obesity. The drugs were also subject to strict rules regarding contraindications.In the presence of the following diseases and medical conditions, treatment with sibutramine-containing drugs should not be performed: Cardiovascular diseases, liver and kidney dysfunction, hyperthyroidism and glaucoma. In addition, for safety reasons, pregnant and breastfeeding women, as well as children and adolescents under 18 years of age, should not take sibutramine.
Risks and side effects
In addition to the sometimes life-threatening side effects that can occur during treatment with sibutramine and due to which medications containing this active ingredient have lost their approval, a number of other harmful side effects have been observed. These include sleep disturbances, constipation, dry mouth, headache, vomiting, and numbness. In addition, adverse side effects in the psychological and neural areas have also been noted. During treatment, drowsiness, paresthesias, taste disorders, skin rashes, excessive sweating (hyperhidrosis), anxiety, and daytime sleepiness may occur. The effects of sibutramine on the mind may be euphoric and antidepressant. The effects are similar to some antidepressants, which are also SNRIs. Sibutramine is now also on the list of banned drugs.
