When depression is not responding to antidepressants then reevaluation of diagnosis becomes very important. One large historical cohort study conducted in Taiwan found a significant relationship between bipolar disorder and treatment resistant depression. It was published in British Journal of Psychiatry 2012 January.
According to this study, history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar disorder. Around 7.6 -12.1% of those with the diagnosis of unipolar depression was subsequently changed to bipolar disorder. In this group people with treatment resistant depression showed higher rate of change to a bipolar diagnosis (25.6 -26.6%). This study was conducted from the data of 3500 participants. Data was collected from Taiwan National Health Insurance database. It is a database that covers almost entire (99%) population of Taiwan.
Bipolar disorder can present initially as a depressive disorder. At that time clinicians would diagnose it as a unipolar major depressive episode. But resistance to treatment is a good predictor of subsequent change into bipolar illness. In addition, it would rationalize adding mood stabilizer medication such as Lithium to augment anti depressant medications. Addition of mood stabilizing anti psychotic such as Zyprexa (Olanzapine) also help such patients.