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Amineptine (Survector, Maneon, Directim, Neolior, Provector, Viaspera) is an atypical tricyclic antidepressant (TCA) that selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect.

Introduced in Francemarker in 1978 by the pharmaceutical giant Servier and marketed under the trade name Survector, amineptine soon gained a reputation for abuse due to its short-lived, but pleasant, stimulant effect experienced by some patients. (This is to be distinguished from its antidepressant effect, which appears in approximately 7 days after commencing treatment.) This led to the Food and Drug Administration suspending the marketing authorisation for Survector in 1999 and France withdrew it from the market, however several developing countries continued to produce it up until 2005.

Currently amineptine is off-patent and very difficult to obtain. Rare cases of hepatotoxicity, some serious, have been reported, but these were thought to be due to a genetic predisposition.

Therapeutic indications

Approved

Amineptine was approved in France for severe clinical depression of endogenous origin in 1978.

Unapproved/Off-Label/Investigational

Parkinson's Disease, amotivational syndromes, ADHD (Attention Deficit/Hyperactivity Disorder)

Mechanism of action



Side effects

Dermatological

Severe acne due to amineptine was first reported in 1988 by various authors—Grupper, Thioly-Bensoussan, Vexiau, Fiet, Puissant, Gourmel, Teillac, Levigne, to name a few—simultaneously [Article in French] List of Library Holdings Worldwide [Article in French] List of Library Holdings Worldwide [Article in French] List of Library Holdings Worldwide [Article in French] List of Library Holdings Worldwide [Article in French] List of Library Holdings Worldwide in the same issue of Annales de Dermatologie et de Venereologie and in the 12 March 1988 of The Lancet. List of Library Holdings Worldwide A year later, Dr Martin-Ortega and colleagues in Barcelona, Spain reported a case of "acneiform eruption" in a 54-year-old woman whose intake of amineptine was described as "excessive." [Article in Spanish] List of Library Holdings Worldwide One year after that, Vexiau and colleagues reported six women, one of whom never admitted to using amineptine, getting severe acne concentrated in the face, back and thorax, the severity of which varied with the dosage. List of Library Holdings Worldwide Most of them were treated unsuccessfully with isotretinoin (Accutane) for about 18 months; two of the three that discontinued amineptine experienced a reduction in cutaneous symptoms, with the least affected patient going into remission.

This can be seen as a general side effect of central dopamine enhancement, due to the inhibitory effect of dopamine on prolactin, with the subsequent increase in testosterone output, leading in turn to the same potential for acne as is typical of pubescents.

Psychiatric

Psychomotor excitation can very rarely occur with this drug.
  • Nervousness (very rare)
  • Irritability (very rare)
  • Insomnia (very rare)
  • Suicidal ideation (very rare) Seen in beginning of treatment. By lifting of psychomotor inhibition. Increase monitoring at the beginning of treatment.


Cardiovascular



Hepatic

Amineptine can very rarely cause hepatitis, of the cytolytic, cholestatic varieties. [Article in French] List of Library Holdings Worldwide Amineptine-induced hepatitis, which is sometimes preceded by a rash, is believed to be due to an allergic reaction. It resolves upon discontinuation of the offending drug. The risk of getting this may or may not be genetically determined.

Additionally, amineptine is known to rarely elevate transaminases, alkaline phosphatase, and bilirubin. [Article in French] List of Library Holdings Worldwide

Mixed hepatitis, which is very rare, generally occurs between the 15th and 30th day of treatment. Often preceded by sometimes intense abdominal pains, nausea, vomiting or a rash, the jaundice is variable. Hepatitis is either of mixed type or with cholestatic prevalence. The evolution was, in all the cases, favorable to the discontinuation of the drug. The mechanism is discussed (immunoallergic and/or toxic).
    • Concours Med 1982; 104:5733-5734.


In circa 1994 Spain, there was a case associating acute pancreatitis and mixed hepatitis, after three weeks of treatment.

Lazaros and colleagues at the Western Attica General Hospital in Athens, Greecemarker reported two cases of drug induced hepatitis 18 and 15 days of treatment.

One case of cytolytic hepatitis occurred after ingestion of only one tablet.

Gastrointestinal

  • Acute pancreatitis (very rare) A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment.

Immunological

In 1989, Sgro and colleagues at the Centre de Pharmacovigilance in Dijonmarker reported a case of anaphylactic shock in a woman who had been taking amineptine.

Effects on the unborn child

  • Non-teratogenic in animals
  • Lacking information in humans


Abuse and Dependence

The risk of addiction is low, but it is there nonetheless. Between 1978 and 1988, there were 186 cases of amineptine addiction reported to the French Regional Centres of Pharmacovigilance; an analysis of 155 of those cases found that they were predominantly female, and that two-thirds of cases had known risk factors for addiction. [Article in French] List of Library Holdings Worldwide However, a 1981 study of known opiate addicts and schizophrenia patients found no drug addiction in any of the subjects. [Article in French] List of Library Holdings Worldwide In a 1990 study of eight amineptine dependence cases, the gradual withdrawal of amineptine could be achieved without problems in six people; in two others, anxiety, psychomotor agitation, and/or bulimia appeared. [Article in French] List of Library Holdings Worldwide

Precautions for use



Contraindications

  • Chorea
  • MAO inhibitors
  • Children less than 1 year of age
  • Hypersensitivity: Known hypersensitivity to amineptine, in particular antecedents of hepatitis after dosage of the product.


See also

References

External links




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