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Since the serendipitous discovery of imipramine, in 1957, different classes of antidepressant drugs have beeb used to treat depressive syndromes. Although their efficacy is well established, still 30-40% of patients do not show a significant response (> 50% reduction in baseline score on the Hamilton rating Scale for Depression-HAMD) to therapeutic doses of antidepressant medications administered for 6-8 weeks of treatment, whilr 60-70% fail to achieve full remission (17-item HAMD < 7) (Moncrieff and Kirsch, 2005). Partial remission has been associated with a higher recurrence, a greater functional impairment and a worse quality of live (Fava et al., 2002; Tranter et al., 2002). All antidepressant have a lag phase and it takes at least 3-4 weeks to observe the real effect of treatment administration (Quitkin et al., 1996). Such a delayed response may increasethe patients’ suffering and the risk of suicidal behanior and early discontinuation of treatment. Patients have to stay in hospital for longer periods and this results in higher costs. Therefore early identification of responders to a specific antidepressant tratment would be of great usefulness both from a clinical and economical point of view. Unfortunately, in spite of some evidence concerning the predictive power of demographic characteristics, illness features ans social dactors (Esposito and Goodnick, 2003; Goodnick, 1996; Nierenberg, 2003), none of such variables could unequivocally be linked to treatment outcome and antidepressant choice is still based on a trial and error procedure. Inherited differences in drug response have been described for a variery of compounds supporting the incluence of genetics factors on treatment of outcome (Roden and George, 2002; Weinshilboum, 2003). This has been investigated in antidepressant short term tratment (O’ Reilly et al., 1994; Orsini, 1987; Pare et al., 1962; Serretti et al., 1998). Further, one important determinant in treatment decision making is the ocurrence of side effects, which can negatively impact compliance. This was reported to be of 40% to 90% in differents studies of antidepressant drugs with an average of 65% (Cramer and Rosenheck, 1998). As the prevalence and severity of side effects follow interindividual variations, it is reasonable to hypothesize a genetic basis for drug tolerability (Murohy et al., 2003a). The present paper will review the literature concerning genetic influence on the efficacy and tolerability of antidepressants. Traditional approaches based on the analysis of a candidate genes which act throughout pharmachodynamic and pharmachokinetic mechanisms are now integrated by complementary genome-wide approaches (Brown and Botstein, 1999).

Palabras clave: Antidepressant drugs depressive syndromes.

2008-01-22   |   1,054 visitas   |   Evalua este artículo 0 valoraciones

Vol. 30 Núm.6. Noviembre-Diciembre 2007 Pags. 1-12 Salud Ment 2007; 30(6)