5,15 An association between towards treatment resistance and specific depressive Nilotinib Leukemia subtypes has been reported by researchers.5

Atypical depression with panic may be relatively resistant, to tricyclic antidepressants (TCAs),but responsive to monoamine oxidase inhibitors (MAOIs).16 Psychotic and melancholic depression Inhibitors,research,lifescience,medical may also be resistant to treatment, requiring the use of additional treatment strategies. Factors such as greater number of somatic symptoms and reported history of childhood emotional abuse and sequelae of that abuse may be associated with treatment resistance in depressed outpatients.17,18 Factors related to antidepressant treatment Up to 20% of patients who are termed treatment, resistant may actually be intolerant to the medication.19 The use of concomitant medications may interfere Inhibitors,research,lifescience,medical with the absorption and metabolism of antidepressants, and interfere with response. Inadequate treatment of earlier episodes may lead to treatment resistance possibly due to kindling and sensitization at the receptor and synaptic levels.20 Inhibitors,research,lifescience,medical Factors related to the patient and environment These include

partial compliance or noncompliance, rapid metabolism, and the presence of severe psychosocial stressors. Partial compliance or noncompliance are important causes of treatment resistance, as up to 50% of patients do not Inhibitors,research,lifescience,medical take the medication as prescribed, and tend to stop treatment when symptoms remit.7 Individual differences in drug metabolism may result, in suboptimal blood levels in patients who are rapid metabolizers and contribute to treatment resistance.7 Nutritional status of the patient must be assessed, as deficiencies in folate, thiamine, vitamin B6, vitamin

B12, copper, Inhibitors,research,lifescience,medical and zinc may contribute to treatment resistance.21,22. The presence of psychosocial stressors and the relative absence of family support may also predict poor outcome for depressed patients.23 Brain imaging studies Although neuroimaging is a useful tool to assess brain function in depression, few published brain AV-951 imaging studies have compared brain function in TRD and treatmentresponsive or non-treatment-resistant depression (non-TRD). Shah and coworkers found that patients with chronic TRD had reduced gray matter density in the left temporal cortex including the hippocampus, with a trend toward reduction in the right hippocampus.24 These authors also reported right frontostriatal atrophy and subtle magnetic resonance imaging (MRI) changes in the left hippocampus among patients with resistant depression.25 A single photon emission computed tomography (SPECT) found a significant increase in hippocampusamygdala activity in TRD patients compared with non-TRD patients and healthy controls.