CYP2D6 gene polymorphism is considered a main obstacle in the process of drug metabolism under clinical diseases that affect pharmacokinetics of ~25% of antidepressants and other drugs. Inter-individual variation occurs in the amount and functional activity of CYP2D6 enzyme produce undesirable side effects. The primary aim of current research is to evaluate gene and genotypic frequencies of CYP2D6 *1 extensive metabolizer, *4 poor metabolizer and *10 intermediate metabolizer allelic variants among depressed patients and compared with normal subjects and other populations. Human genomic DNA was isolated. Genotyping was performed by Polymerase chain reaction followed by restriction endonucleases digestion for variants analysis. The results indicated gene frequency of CYP2D6*1 was 59% (CI 49.6,68.3%) in normal subjects whereas, CYP2D6*4 was 13% (CI 3.7, 22.3%) and CYP2D6*10 was 54% (44.7, 63.3%) predominantly found in depressed patients. The results demonstrate pronounced association of CYP2D6 *4 and *10 allelic variants with patient’s drug response activity.