CYP2D6 is an enzyme family which is found in the liver and responsible to metabolize/digest antidepressants drugs and producing drug response. It has been found that changes in CYP2D6 gene produce different forms of enzymes which do not produce therapeutic effect in depressed patients because they unable to metabolize drugs properly and uncured the disease as a result they bear mental issues and unhealthy life. We designed a study to evaluate the CYP2D6 gene which is very prevalent in Asian countries including Pakistan and show improper drug digestion ability that affect therapeutic responses. We determined CYP2D6 gene polymorphism in depressed patients and compared them with normal people from a sub-set of Karachi population. For conducting this research DNA was separated from patient’s blood and run on PCR machine to visualize the CYP2D6 gene changes between depressed patients and normal people. Results were meaningful and clearly showed the differences between patients and normal with respect to antidepressants drugs responding ability and indicating why patients poorly respond drugs and suffering from depression. Because drug metabolism or drug digestion is a complex phenomenon that is dependent on genetic and environmental factors. CYP2D6 gene changes may alter the antidepressants drugs metabolism. Therefore, gene testing system need to be established that may help doctors for analyzing maximum patient’s gene profile and to prescribe right amount of antidepressants drugs dosage for minimizing the rate of depression.