The British Journal of Psychiatry
Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study
Cheng-Ta Li, Ya-Mei Bai, Yu-Lin Huang, Ying-Sheue Chen, Tzeng-Ji Chen, Ju-Yin Cheng, Tung-Ping Su



People with major depressive disorder who fail to respond to adequate trials of antidepressant treatment may harbour hidden bipolar disorder.


We aimed to compare the rates of a change in diagnosis to bipolar disorder among people with major depressive disorder with stratified responses to antidepressants during an 8-year follow-up period.


Information on individuals with major depressive disorder identified during 2000 (cohort 2000, n = 1485) and 2003 (cohort 2003, n = 2459) were collected from a nationally representative cohort of 1 000 000 health service users in Taiwan. Participants responding well to antidepressants were compared with those showing poor responses to adequate trials of antidepressants.


In 7.6–12.1% of those with a diagnosis of unipolar major depressive disorder this diagnosis was subsequently changed to bipolar disorder, with a mean time to change of 1.89–2.98 years. Difficult-to-treat participants presented higher rates of change to a bipolar diagnosis (25.6% in cohort 2000; 26.6% in cohort 2003) than easy-to-treat participants (8.8–8.9% in cohort 2000; 6.8–8.6% in cohort 2003; P<0.0001). Regression analysis showed that the variable most strongly associated with the change in diagnosis was antidepressant use history. The difficult-to-treat participants were associated most with diagnostic changing (cohort 2000: odds ratio (OR) = 1.88 (95% CI 1.12–3.16); cohort 2003: OR = 4.94 (95% CI 2.81–8.68)).


This is the first large-scale study to report an association between antidepressant response history and subsequent change in diagnosis from major depressive disorder to bipolar disorder. Our findings support the view that a history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar diathesis.