**3.1 Mismatch of impaired monoamines and prescribed antidepressant drugs**

One of the causes of treatment-resistant depression could be explained by the possibility that there are different types of depression whose pathophysiology differs in which monoamine is involved (5-HT, NA, DA, or two or more monoamines). The problem is that there are no objective diagnostic tools to differentiate which monoamine is involved in the pathophysiology of depressive symptoms of individual patients. In fact, as mentioned before, animal studies have suggested that there are various types of depression that differ in the monoamine(s) involved [10, 11, 13, 14, 18]. In clinical practice, SSRIs are most commonly prescribed as first-line antidepressant drugs without any distinct evidence that the depressive symptoms of patients are due to 5-HT deficiency. At present, it is difficult for clinicians to correctly administer antidepressant drugs to individual patients with depression. If patients with depression are not administered antidepressant drugs that are able to regenerate the particular monoamine axons that are damaged in their case, they may suffer from treatment-resistant depression.
