Examining Rates of Conversion From Unipolar Depression to Bipolar Disorder

Patients with unipolar depression are diagnosed as such unless hypomania or mania develop, which would indicate a diagnosis of bipolar disorder. Compared with those with unipolar depression, patients with bipolar disorder generally have worse outcomes, including higher rates of recurrent episodes, and they require more complex treatment strategies.^1-3

Findings from prior research on conversion rates are mixed, with some studies demonstrating varying rates of conversion over specified time periods, and other results showing a consistent, linear rate of 1.25% per year.^3-5 Additionally, potential predictors of conversion had not previously been explored before the present investigation. As reported in Bipolar Disorders in August 2017, researchers at the University of Copenhagen in Denmark conducted the first systematic review and meta-analysis to examine the risk for conversion from unipolar depression to bipolar disorder, as well as potential predictors of conversion.⁶

The researchers conducted a review of relevant studies with publication dates ranging from 1950 to 2016, in which adolescent or adult patients with a diagnosis of depressive disorder were followed for at least 1 year, and which included data pertaining to the subsequent diagnosis of mania, hypomania, or bipolar disorder in these patients. Only studies that used survival analysis were included in the meta-analysis.

Ultimately, 11 studies met the inclusion criteria, consisting of a combined total of 77,066 patients. The results show the highest conversion risk during the first few years after the start of the study, with a gradual reduction over time, from 3.9% in the first year to 3.1% in years 1 and 2, 1.0% in years 2 through 5, and 0.8% in years 5 through 10. After 10 years, the cumulative risk for conversion increased to 12.9%. 

The following 8 potential risk factors for conversion were also assessed: gender, age at onset of unipolar depression, number of depressive episodes, treatment resistance to antidepressants, family history of bipolar disorder, psychotic depression, chronic depression, and depression severity.

None of these factors was found to predict conversion consistently, with results split roughly equally between supporting or not supporting certain factors as predictive of conversion. For example, 2 of 4 studies reported a significant link between conversion to bipolar disorder and family history of the disease, and 4 of 7 studies suggested an association between conversion and young age at first onset of depression. Both of these factors have been proposed to increase conversion risk.

The authors state that these divergent findings may be explained by differences in methodology used in the various studies. “Future studies should start with prospective assessment from first episode, include prospective follow-up of different types of bipolar disorder in different recruitment settings, and use survival analysis in the statistical analyses,” they wrote.

Psychiatry Advisor checked in with Ruben C. Gur, PhD, professor of psychology in the department of psychiatry at the Perelman School of Medicine of the University of Pennsylvania (who was not involved in this study), regarding the significance of these findings, as well as future needs in this area.