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Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of many antidepressants. It is characterized by a high individual variability in catalytic activity mainly due to >75 CYP2D6 alleles that determine metabolizer status. The role of CYP2D6 genetic polymorphism in the metabolism of amitriptyline and şuoxetine was previously demonstrated [LLerena et al, 2004]. Herein, we analyzed the relevance of CYP2D6 genetic polymorphism for the clinical response to the antidepressant drugs şuoxetine and amitriptyline. Sixty-five patients (DSM-IV) diagnosed with major depression and a score equal or greater than 17 on the Hamilton-Depression (HAM-D) were prospectively studied. They were treated either with şuoxetine or amitriptyline under antidepressant monotherapy. The informed written consent was obtained from all patients. Clinical Response was evaluated with HAM-D. The patients were evaluated every month. A two months period evaluation is reported here. The patients with a 50% decrease on HAM-D were considered as "responders." CYP2D6 genotyping was assayed by PCR-RFLP and RT-PCR. The first month evaluation showed that 49 out of the initial 65 remained (16 dropped-out) in the study and second month evaluation showed that 41 patients remained (8 more dropped-out). Among responders there were 56.6% and 60% to şuoxetine, and 50% and 70% to amitriptyline, at first and second follow up evaluations, respectively. The responders were characterized by presenting one or two CYP2D6 active genes. Furthermore, the number of active genes was related to better clinical response in both drugs. The percentage of responders was higher for those with two active genes than for patients carrying just one: (a) şuoxetine, 81 % vs.18 % at first month; 87% vs. 13% at second month; (b) amitriptyline, 60 % vs.40 % at first month; 83% vs. 17% at second month. All ultrarapid metabolizers (n=3 UMs; those with more than two CYP2D6 active genes) were found to drop out during the first month. The only poor metabolizer patient in the study (PM; with none CYP2D6 active genes) was found among "non-responders" in both follow-up evaluations. The number of CYP2D6 active genes seems to be related to clinical response to the antidepressant drugs amitriptyline or şuoxetine. Among responders, the frequency of patients carrying two CYP2D6 active genes is higher than those with one copy. Moreover, UMs and PMs were not found in this group.
Grants: Supported by grants from the Spanish Ministry of Health Instituto de Salud Carlos III and EU-FEDER PI10/02758, CP06/00030 (PD); AEXCID (9IA006) Junta de Extremadura and EU-FEDER (BS10023) and Consejo Nacional de Ciencia y Tecnología de México (Nº 59366). This work was coordinated by Network Red Iberoamericana de Farmacogenética y Farmacogenómica (CYTED206RT0290). Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S187