It is well documented in the literature that there is high prevalence of depression in various diseases and is also a risk factor for the development of certain diseases, such as cardiovascular disease or diabetes. Depression can delay the convalescence and may have effects on treatment states. Pharmacological treatments for depression are based on increasing activity of neurotransmitters which are normally diminished in this disease. Various intrinsic or extrinsic factors play role for the development of depression. Treatments vary according to the type of depression. Hence, diagnosing the exact cause of depression is very important. The adverse effects of antidepressant drugs on other disease conditions in a depressed patient should be considered, particularly on the central nervous system and the cardiovascular system. The interactions of various antidepressants may cause the "Serotonin Syndrome" by synergy effect. There are also interactions with other drugs at the kinetic level due to the role of cytochrome P450 (CYP450) in the metabolism of antidepressants and many others (drugs or molecules). These interactions can be competitive or non-competitive with a result of agonism (synergies) or antagonism, with the change of relative effects of each one. Because antidepresant effect is at long term, the quick substitution of one antidepressant with other usually gives mixed effects of both and interactions at the beginning. Withdrawal should be gradual otherwise, it may cause discontinuation syndrome. The symptoms of this syndrome should not be confused with the patient's symptoms. The worsening of other ailments and enlargement of convalescence can be diminished with right type of antidepressant treatment.