Uso da amitriptilina e a importância da sua substituição pela fluoxetina durante a prenhez: efeitos reprodutivos, gestacionais e no desenvolvimento da prole

Abstract

The depression have been described as the most pathology that affects people, and the women are the main victims of the illness, according to the World Health Organization (WHO). The depression development during the pregnancy can cause harm to the women and their descendants, therefore in some cases the drug treatment is necessary. However, there are few studies about the pregnancy with use the antidepressant medicines. Because this, the goal of this study is evaluate the amitriptyline (AMT), during the reproductive stage and pregnancy period in mouse, just like the substitution practice by fluoxetine (FLX), in the end of germinal period and possible effects in pregnancy, in after birth and in offspring development. Swiss Female mouses were treated with AMT (20 mg/Kg) 10 days and during mating, via orogastric gavage and divided in two experimental groups. In first AMT was sustained during all pregnancy and second group was realized the substitution of AMT by FLX (10 mg/Kg) on the 14th pregnancy day (PD). In the control group, female were treated with medicine’s eluent solution, Carboxymethyl cellulose 1%. During the pregnancy, it were accompanied the weight and maternal ingestion and on 18th PD some females were euthanized for gestational and placental analysis. In other female group, the gestation was at term, the offspring were normalized in 6 puppies (3 males / 3 female) for maternal behavior evaluation, offspring development analysis on first 30 life days, when were realized depression and anxiety analysis tests. In the results, it occurred a reduction of 52,95% in the pregnancy rate for treated mothers, besides an increase in the stillbirth rate and newborn death, in the treatment with the AMT. The mothers treated weight with AMT and AMT+FLX, showed significant diference on last pregnancy days, the weight and Intrauterine growth restriction (IURG) weren’t changed. The AMT group placente showed evidente difereces: spongiotrophoblast increase, labyrinttrophoblast decrease, edema presence and degeneration areas. This efects were softened in AMT+FLX group. It wasn’t verified offspring teratogenic problem, but on the puberty the AMT group puppies, showed weigth and size smaller. However, female anus/genital distance (AGD) incresed. It was observed, rupture of the incisors delay in both treatments. The maternal care didn’t show significant diferences with medicines using, together with the young offspring anxiety and depression tests. In conclusion, data points out that treatment with drugs dicrease pregnancy chance. The AMT treatment causes importante placental changes, besides of increase stillbirth number and newborn death, that looks like the preeclampsia frame. However, the change by FLX looks like to soften this problems. AMT still is associated a weigth and offspring size decrease and female puppies masculinization. But, treatments aren’t sound of to intervene in maternal behavior, or young offspring depression and anxiety patterns. Within these findings, can be verified that clinical practice AMT by FLX substitution sounds of to be the best medicine management.