Appetite suppressant: in France, prohibited, without a prescription?

Definition: what is an anorectic drug?

Also called appetite suppressantit is a drug that induces a feeling of early satiety or even a complete lack of hunger. After administration, several signals are sent to the brain to inform it that the stomach is full. Satiety is therefore quickly felt.

How does an appetite suppressant work?

In the body, food intake is regulated on the one hand by ghrelin (hormone that increases appetite) and leptin (hormone that decreases appetite). On the other hand, food intake is controlled by the hedonic system based on the pursuit of pleasure. Indeed, the ingestion of food is associated with a feeling of pleasure, it activates the same neural circuits as certain addictions. This pleasure is achieved by release of dopamine, serotonin or endorphins. Thus, certain drugs allowing the production of these substances can induce satiety. Anorectic drugs have different modes of action at the level of neurons:

• they increase the amounts of serotonin, called the happiness hormone. This is the case with serotoninergic anorectics such as certain antidepressants and certain amphetamine derivatives.
• they increase the amounts of dopamine, called the pleasure hormone. They are amphetaminergic anorectics.
• they reproduce the effects of leptin, a hormone that induces satiety. For example, the metreleptin drug Myalepta® is a leptin analogue.
• they produce endorphins (substances that act on the same receptors as opioids). This action is exerted by naltrexone at low doses.

Many medications can cause a side effect that looks like a loss of appetite. However, the mechanism of action involved remains unknown for some of them.

What are the indications of an anorectic?

An anorectic drug allows reduce the amount of food consumed or even reduce seizures in a bulimic patient. This type of treatment is mainly used in cases of overweight or obesity to induce weight loss. Many drugs responsible for anorexia (partial or total loss of appetite) have other indications since their anorectic properties constitute an undesirable effect and not the effect initially sought.

What anorectic drugs are authorized in France?

Marketing authorizations (AMM) for anorectic drugs were suspended in France from 1999 and then withdrawn in 2006. No drug can be prescribed for weight loss. On the other hand the Prozac has an MA forbulimia treatment “in addition to psychotherapy, in reducing the frequency of bulimia attacks and vomiting or taking laxatives” specifies theANSM. THE other molecules that have anorectic properties are not allowed to be prescribed for weight loss or to treat bulimia. If they are used for these purposes, it is a misappropriation of their strictly prohibited use. For example :

► the antiepileptics as Epitomax® (topiramate) and Zonegran® (zonisamide). In several countries, a combination of topiramate and phentermine (amphetamine derivative banned in France) is indicated in the treatment of obesity.
► the drug Fintepla® based on fenfluramine (derived from amphetamine) is available in hospitals to treat epilepsy, it is part of the same family as benfluorex (molecule of Mediator®).
►another amphetamine derivative, methylphenidate, induces a decrease or even a total absence of appetite. This molecule is found in the specialties Ritalin®, Quasym® with an indication in attention deficit disorder with or without hyperactivity (ADHD). The initiation of one of these treatments in children should lead to regular monitoring of weight and appetite.
► One combination of naltrexone (treatment of alcohol withdrawal) and bupropion (treatment of smoking cessation) is marketed in the United States to treat obesity. Studies have shown the effectiveness of this treatment on appetite regulation. These molecules are available individually in France.
► Studies on the baclofen (treatment of alcohol withdrawal and a type of muscle twitching) have shown spectacular results on the frequency of food compulsions by inducing satiety.
► Similarly, the Myalepta® specialty (indicated in patients with lipodystrophy) has effects comparable to leptin (an appetite reducing hormone).
Other drugs may cause a decrease in appetite, but not all are diverted from use due to their unproven or low anorectic properties. This is the case, for example, of amiodarone (antiarrhythmic), vitamin D (in case of overdose), metronidazole (antiparasitic and antibiotic). In addition, some antidepressants are anorectic like sertraline, paroxetine, citalopram, escitalopram (those of the same family as fluoxetine) and Laroxyl®. Orlistat® is the only drug indicated in the treatment of obesity, however it is not an anorectic. Indeed, it blocks the digestion of dietary fats, but has no effect on satiety.

Which appetite suppressants have been banned in France?

The best known is the Mediator® (benfluorex), an amphetamine derivative. This drug was normally indicated in overweight type 2 diabetic patients. Yet it has been diverted from its use by being prescribed as an appetite suppressant in people without diabetes to help them lose weight. Misuse of this drug has caused many deaths from malfunctioning heart valves. This phenomenon has been the subject of a major media scandal. Currently, all amphetamine derivatives are no longer marketed in France, except fenfluramine and methylphenidate. These derivatives include amfepramone, sibutramine, dexfenfluramine, phentermine, clobenzorex, mefenorex, and fenproporex. They were indicated in the management of overweight and obesity in type 2 diabetic patients but, like the Mediator®, were frequently misused.

Can you buy appetite suppressants without a prescription?

No, in France, anorectic drugs are only available on prescription. Only natural appetite suppressants (below) are available over the counter.

What are the side effects and dangers of appetite suppressants?

Fluoxetine (the only drug authorized for its anorectic action) frequently causes weight loss, insomnia, anxiety, headaches, dizziness, tremors, heart palpitations, skin rashes and digestive disorders (diarrhoea, nausea). More rarely, this medication is responsible for liver damage and serious allergic reactions.
Amphetamine derivatives have been withdrawn from the market due to their dangerous nature. They were responsible for serious cardiovascular adverse effects such as the risk of stroke or heart attack, pulmonary arterial hypertension, heart valve damage or the risk of drug dependence.

Their use should be avoided in patients with anorexia nervosa.

What are the contraindications of appetite suppressants?

Not all appetite suppressants should be administered in case of allergy to any of the components of the drug. Their use should be avoided in patients with anorexia nervosa. These patients obsessed with their weight tend to divert these drugs for weight loss purposes to lose more weight. Fluoxetine should not be combined with antidepressants from the MAOI family (such as iproniazid) or metoprolol (treatment of heart failure). Other drugs with anorectic properties have their specific contraindications, they should in no way be considered as appetite suppressants.

What are natural appetite suppressants?

Some phytotherapy products are used as natural anorectics:

• apple pectin
• the fucus
• konjac gum
• chia seed
• nopal (or prickly pear)

Once ingested, these herbal products absorb the water contained in the food bolus and swell within the stomach to form a gel that induces a feeling of satiety faster than expected. Note that chia seeds can be responsible for abdominal pain, especially in people who usually consume little fiber. Similarly, the administration of fucus requires special vigilance. Prolonged exposure or an overdose of fucus can increase iodine concentrations in the body and result in diarrhoea, headaches, thyroid disorders (hypothyroidism, hyperthyroidism) and more rarely in heart damage. In aromatherapygrapefruit and mandarin essential oils are used to reduce the feeling of hunger, they have anorectic properties. In micronutrition, Insunea TCA® can be used mainly to reduce sweet food cravings. This dietary supplement contains tryptophan (amino acid precursor of serotonin), knowing that a serotonin intake curbs the appetite.

Sources:
– Public drug database
– Amphetamine appetite suppressants are strictly prohibited in France, 07/01/2021, ANSM
– The High Authority for Health
– Wichtl M., Anton R. Therapeutic plants, 2nd edition. International Tec and Doc-Medical Editions-Lavoisier, 2003.