Search

ResumenLa adicción a diversas sustancias, incluidas las drogas y el alcohol, se origina probablemente en una combinación de factores ambientales y genéticos. Varios estudios familiares, de adopción y de gemelos apoyan la vulnerabilidad genética a la adicción a las drogas. Sin embargo, como ocurre en otros trastornos mentales, la vulnerabilidad genética a la adicción a las drogas parece compleja: estos trastornos no siguen las reglas de la herencia mendeliana. En su lugar, influyen probablemente en ellos múltiples genes de susceptibilidad, cada uno de los cuales contribuye al trastorno. Cuantos más genes son necesarios para un trastorno, más difÍcil es detectar cualquiera de ellos. El papel de los factores ambientales aumenta esta dificultad. Los estudios de asociación que han utilizado el enfoque del gen candidato pueden identificar genes de susceptibilidad para el abuso de drogas con el apoyo de la hipótesis patofisiológica de la enfermedad. Esta revisión se centrará en los estudios clÍnicos y de genética molecular en el abuso de drogas.

SummaryAddiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.

ResumenEn el curso del desarrollo internacional de la tianeptina (T), 18 centros de Bélgica, Italia, México, Portugal, España y Suiza seleccionaron pacientes deprimidos en un estudio doble ciego de grupos paralelos frente a placebo (P) e imipramina (I). La eficacia y seguridad de la tianeptina se valoraron en 187 pacientes internos deprimidos (56% mujeres, 44% varones) que cumplían los criterios para depresión mayor, con episodio único (24,6%) o recurrente (6 6 ,8 %), o trastorno bipolar depresivo (8 ,6 %). Después de un periodo de rodaje de siete días con placebo previo a la inclusión, los pacientes recibieron tratamiento en condiciones de doble ciego con tianeptina (37,5 mg/d), imipramina (150 mg/d) o placebo durante 14 días, incluido un periodo de tres días de aumento diario de la dosis. Después del decimocuarto día y hasta el final de la sexta semana de tratamiento, se introdujo una dosis flexible de acuerdo con la eficacia terapéutica o los acontecimientos adversos potenciales (T: 25-50 mg/d; I: 100-200 mg/d; P: 2-4 cápsulas).

SummaryTianeptine has been shown to be an effective antidepressant versus reference drugs and to be better tolerated than amitriptyline, without the latter's anticholinergic side-effects. Its good acceptability has been confirmed in long-term use (1 year) in large patient groups. In an open pilot trial in endogenous melancholia, tianeptine showed the same activity as would be expected of a conventional antidepressant. This is being verified in a double-blind trial versus maprotiline. In a separate open study, it has demonstrated a potential to prevent relapse and recurrence in depressed patients treated for 1 year. These results are currently being tested versus placebo.

SummaryTianeptine, whose main neurochemical action is to increase 5-HT uptake, significantly decreased alcohol consumption in rats. During a tianeptine long-term treatment study, gamma-GT levels in depressed alcoholic patients decreased, suggesting that this medication could be useful in alcoholism. The role of tianeptine in the prevention of alcoholic relapses is being evaluated in a double-blind placebo-controlled study. Two hundred non-depressed patients satisfying DSM III-R criteria for Psychoactive Substance Dependence (alcohol – daily intake greater than 80 g) will enter the study after alcohol withdrawal. A minimum score of three on the Short-Mast Questionnaire, mean cell volume above 98 f1 and/or gamma-GT more than twice the upper normal value are required. Patients are treated as out-patients and surveyed for 9 months. The maintenance of abstinence is estimated through clinical and laboratory assessments. The alcohol intake is evaluated in patients who relapse. Efficacy is determined secondarily using Clinical Global Impressions Scale, Hopkins Symptom Check List and visual analogue scales. Somatic complaints are collected using AMDP-5. Preliminary results are presented.

SummaryA study was performed in young healthy volunteers in order to test the possible action of tianeptine, a new antidepressant drug, on cognitive performances. Attention tests, memory tests, a non-verbal inductive reasoning test and a sleep questionnaire were used in this double-blind placebo-controlled crossover study. The two one-week drug administration periods were separated by a one-week wash-out period. The methodology permitted us to evaluate the learning effect during the familiarization with the tests and to clear the results of the study from this parameter which could possibly distort analysis. For this large range of tests, the results showed that tianeptine did not affect the level of functioning of the volunteers after their familiarization with the tests. These results are in contrast with those obtained by different authors with classical tricyclic antidepressants.