This investigation was carried out to evaluate genotoxicity of two important antidepressants medications (namely, Sertraline (four Modabex doses) and Carbamazepine (four Tegretol doses) on albino mice, Mus musculus, via molecular and cytological studies. pharmacogenomic gene (Cytochrome P450 4B1 gene) was employed as marker for detecting critical dose for antidepressant drug and monitoring its affect with different doses extracted from exposures, amplified and sequenced. Cytological studies reflected Robertsonian Centric Fusion (RCF), Ring Chromosome (RC), chromosomal aberrations for tests tissue treated with fourth Sertraline dose. Furthermore, Stickiness (S), chromatide deletion (CD), Ring Chromosome (RC) aberrations for bone marrow tissue treated with second Carbamazepine dose. Nevertheless, chromosomal aberrations for tests tissue treated with fourth Sertraline dose. Highly affect of Sertraline dose for tests tissue on was detected for third dose as a result of lowest similarity percentage (60 %) which indicated affection of these doses. Interestingly the same antidepressant drug (Sertraline) with the same dose (third Modabex) which cause highly affect on Cytochrome P450 4B1gene in tests tissue, it recorded lowest affect in bone marrow sample. Based on Cytochrome P450 4B1gene sequence, influence of Sertraline on tests sample was dissentingly as 71, 72, 59, 55 and 69 % of genetic similarity percentage. Highly affect of Carbamazepine was detected under first dose. Second Carbamazepine dose has no influence as a result of Cytochrome P450 4B1gene sequence for untreated and treated with second dose for tests sample. For 68, 83 and 73% of genetic similarity percentage were recorded between Cytochrome P450 4B1gene sequences which isolated form bone marrow (with different doses) and Cytochrome P450 4B1reference gene sequence. Genetic evaluation of Sertraline and Carbamazepine cleared that, third Modabex dose and first Tegretol dose could be considered as critical doses.