Treatment resistance in unipolar depression: Is it an iatrogenic phenomenon caused by antidepressant treatment of patients with a bipolar diathesis?

Major depressive disorder is a common psychiatric illness that is considered generally treatable; however, there are some patients who fail to respond in spite of adequate trials of antidepressants. Clinical factors known to contribute to treatment resistance include psychiatric and physical comorbidity, undiagnosed bipolarity, and treatment non-adherence. There is also emerging evidence that the use of antidepressants in some 'unipolar' patients may lead to a pattern of progressive diminution of therapeutic response and ultimately treatment resistance. A large number of these patients may have a bipolar diathesis even though there are no symptoms of hypomanic, manic or mixed episodes. It is hypothesized that the widespread and injudicious use of antidepressants in patients with a bipolar diathesis might result in treatment-induced resistant depression. Furthermore, attempts to manage the antidepressant-led mood instability might cause increased utilisation of other psychotropic drugs including sedative/hypnotics, neuroleptics and mood stabilisers and contribute to polypharmacotherapy.