Critical Predictors for the Early Detection of Conversion From Unipolar Major Depressive Disorder to Bipolar Disorder: Nationwide Population-Based Retrospective Cohort Study
Authors: Hu Ya-Han , Chen Kuanchin , Chang I-Chiu , Shen Cheng-Che 
Published: February 2020

Background
Unipolar major depressive disorder (MDD) and bipolar disorder are two major mood disorders. The two disorders have different treatment strategies and prognoses. However, bipolar disorder may begin with depression and could be diagnosed as MDD in the initial stage, which may later contribute to treatment failure. Previous studies indicated that a high proportion of patients diagnosed with MDD will develop bipolar disorder over time. This kind of hidden bipolar disorder may contribute to the treatment resistance observed in patients with MDD.

Objective
In this population-based study, our aim was to investigate the rate and risk factors of a diagnostic change from unipolar MDD to bipolar disorder during a 10-year follow-up. Furthermore, a risk stratification model was developed for MDD-to-bipolar disorder conversion.

Methods
We conducted a retrospective cohort study involving patients who were newly diagnosed with MDD between January 1, 2000, and December 31, 2004, by using the Taiwan National Health Insurance Research Database. All patients with depression were observed until (1) diagnosis of bipolar disorder by a psychiatrist, (2) death, or (3) December 31, 2013. All patients with depression were divided into the following two groups, according to whether bipolar disorder was diagnosed during the follow-up period: converted group and nonconverted group. Six groups of variables within the first 6 months of enrollment, including personal characteristics, physical comorbidities, psychiatric comorbidities, health care usage behaviors, disorder severity, and psychotropic use, were extracted and were included in a classiﬁcation and regression tree (CART) analysis to generate a risk stratification model for MDD-to-bipolar disorder conversion.

Results
Our study enrolled 2820 patients with MDD. During the follow-up period, 536 patients were diagnosed with bipolar disorder (conversion rate=19.0%). The CART method identified five variables (kinds of antipsychotics used within the first 6 months of enrollment, kinds of antidepressants used within the first 6 months of enrollment, total psychiatric outpatient visits, kinds of benzodiazepines used within one visit, and use of mood stabilizers) as significant predictors of the risk of bipolar disorder conversion. This risk CART was able to stratify patients into high-, medium-, and low-risk groups with regard to bipolar disorder conversion. In the high-risk group, 61.5%-100% of patients with depression eventually developed bipolar disorder. On the other hand, in the low-risk group, only 6.4%-14.3% of patients with depression developed bipolar disorder.

Conclusions
The CART method identified five variables as significant predictors of bipolar disorder conversion. In a simple two- to four-step process, these variables permit the identification of patients with low, intermediate, or high risk of bipolar disorder conversion. The developed model can be applied to routine clinical practice for the early diagnosis of bipolar disorder.