Amineptine (antidepressant): uses, indications and side effects

This Antidepressant drug was indicated for severe depression. It is no longer marketed.

Amineptine is an old antidepressant drug that was marketed for the treatment of severe depression. that was marketed for the treatment of severe depression.

Its stimulant effects and addictive potential led administrations to ban its sale and consumption twenty years ago. Today, this drug is no longer used and is included in the list of controlled substances.

In this article we explain what amineptine is and what are the main characteristics of the group of antidepressants to which it belongs.What is its mechanism of action, and what kind of side effects does it produce.

• Recommended article: "Types of antidepressants: characteristics and effects".

What is amineptine?

Amineptine is an atypical antidepressant drug belonging to the tricyclic antidepressant group.. It was developed and introduced into the market by the French company Servier in the 1970s to treat severe clinical depression of endogenous origin. After its launch, it gained some popularity due to the fact that, apart from the effects of an antidepressant drug, it also produced exciting effects, which were short-lived but very pleasant, according to what the patients themselves experienced.

The stimulant effects caused by this drug led many people to make recreational use of it; moreover, after its marketing spread in several European countries, numerous cases of hepatotoxicity arose due to abusive use, some of them of considerable seriousness, which led the authorities to suspend the authorization for its sale.

In 1999, the marketing of amineptine was banned in Spain.sold under the name Survector, a measure that was extended to several European countries. However, the U.S. Food and Drug Administration (FDA), a key institution worldwide in allowing or not allowing certain drugs to be marketed, has never approved amineptine for sale in the United States.

Currently, amineptine (in its hydrochloride form) is included in Schedule II of UN controlled and controlled substances.

Tricyclic antidepressants

Amineptine belongs to the group of tricyclic antidepressants. These drugs were discovered in the 1950s and have been the first choice for the pharmacological treatment of clinical depression for several decades. Although they are still used for mood disorders (together with MAOIs or lithium, for example), they have now been replaced by another group of antidepressants.

Tricyclic antidepressants share some chemical characteristics with phenothiazines, a group of antipsychotic (or neuroleptic) drugs that are used to alleviate psychotic symptoms and suffering in severe emotional disturbances and mental disorders, despite their marked side effects.

It is precisely because of the large number of side effects caused by tricyclic antidepressants that the use of other types of antidepressants is preferred today. other types of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or selective serotonin reuptake inhibitors (SSRIs), are preferred today. or serotonin and noradrenaline reuptake inhibitors (SNRIs), two groups of antidepressants that generate fewer and milder adverse reactions.

Mechanism of action

Amineptine exerts its effects through the inhibition of dopamine and, to a lesser extent, noradrenaline reuptake. and, to a lesser extent, noradrenaline. One of the peculiarities of the drug is that it also induces the release of dopamine, which explains its stimulant effects; however, the dopamine discharge is relatively mild when compared to other excitatory drugs, such as amphetamine, since its predominant effect seems to be the inhibition of the reuptake of this neurotransmitter, rather than its release.

Unlike dopamine, amineptine does not cause the release of noradrenaline and, therefore, acts only as an inhibitor of its reuptake. Tricyclic antidepressants usually interact with serotonin, adrenergic, dopamine, histamine and acetylcholine (muscarinic-type) receptors; however, this does not occur with amineptine, since their interaction is very weak or practically non-existent.

Side effects

Amineptine shares some of the side effects typical of tricyclic antidepressants (such as insomnia or irritability). (such as insomnia or irritability) and, given its particular pharmacological profile, it also causes organic complications and adverse reactions of its own, which are detailed below.

1. Dermatological problems

Cases of severe acne have been reported in people who have taken amineptine excessively. Specifically, a case was described of a 54-year-old woman whose excessive use of this drug caused an acneiform eruption, characterized by the appearance of papules and pustules in seborrheic areas.

Several cases have also been described of women who, after continued use of amineptine, suffered severe acne on the face, back and thorax, the severity of which varied with the dose.

2. Psychiatric alterations

Another side effect that amineptine consumption can produce is psychomotor excitement, although its occurrence is very infrequent. This includes: insomnia, irritability, nervousness and suicidal ideation.

3. Potential for abuse and dependence

Although the risk of addiction is low, several cases of amineptine dependence have been reported in several centers in France. A study of 155 addicts found that they were predominantly women, and two-thirds of them had known risk factors for addiction.

However, research conducted in the 1980s with opiate addicts and schizophrenic patients found no amineptine addiction in any of the subjects. In another study, in which eight cases of amineptine dependence were analyzed, it was found that gradual withdrawal of the drug was achieved without problems in six of the individuals, and in the other two, symptoms of anxiety, psychomotor agitation and bulimia were observed.

4. Hepatic complications

Amineptine may rarely cause hepatitis (cytolytic and cholestatic). It has been suggested that hepatitis induced by this drug, which is sometimes preceded by a rash, may be due to an allergic reaction and resolves upon discontinuation. In addition, it is known that amineptine does not usually elevate transaminases, alkaline phosphatase and bilirubin.

Mixed hepatitis, which is very rare, usually occurs between days 15 and 30 of treatment with this antidepressant. It is often preceded by abdominal pain (sometimes severe), nausea, vomiting, rash and jaundice (variable). The evolution of the condition is usually favorable if treatment with amineptine is discontinued.

In Spain, in the mid-1990s, a case was identified in which acute pancreatitis and mixed hepatitis were associated after three weeks of treatment with the drug.

5. Cardiovascular problems

Although rare, arterial hypotension, palpitations (hard, rapid and/or irregular heartbeat) and vasomotor episodes or syncope (with transient loss of consciousness, with spontaneous recovery and without sequelae) may occur after amineptine consumption.

Bibliographic references:

• Domingo, J. S., Marco, M. S., & Echebaría, R. U. (1994). Hepatic and pancreatic injury associated with amineptine therapy. Journal of clinical gastroenterology, 18(2), 168.

• Garattini, S., & Mennini, T. (1989). Pharmacology of amineptine: synthesis and updating. Clinical neuropharmacology, 12, S13-8.

• Vaugeois, J. M., Corera, A. T., Deslandes, A., & Costentin, J. (1999). Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine reuptake inhibitor. Pharmacology Biochemistry and Behavior, 63(2), 285-290.