Patterns and predictors of conversion to bipolar disorder in 91 587 individuals diagnosed with unipolar depression

Objective: Conversion from unipolar depression (UD) to bipolar disorder (BD) is a clinically important event that should lead to treatment modifications. Unfortunately, recognition of this transition is often delayed. Therefore, the objective of this study was to identify predictors of diagnostic conversion from UD to BD. Method: Historical prospective cohort study based on 91 587 individuals diagnosed with UD in Danish hospital psychiatry between 1995 and 2016. The association between a series of potential predictors and the conversion from UD to BD during follow-up (702 710 person-years) was estimated by means of Cox regression with death as competing risk. Results: During follow-up, 3910 individuals with UD developed BD. The cumulative incidence of conversion was slightly higher in females (8.7%, 95% CI: 8.2-9.3) compared to males (7.7%, 95% CI: 7.0-8.4). The strongest predictor of conversion from UD to BD was parental history of BD (adjusted hazard ratio (aHR) = 2.60, 95% CI: 2.20-3.07)). Other predictors included psychotic depression at the index UD episode (aHR = 1.73, 95% CI: 1.48-2.02), a prior/concomitant non-affective psychosis (aHR = 1.73, 95% CI: 1.51-1.99), and in-patient treatment at the index episode (aHR = 1.76, 95% CI: 1.63-1.91). Conclusion: Diagnostic conversion from UD to BD is predicted by severe depression requiring in-patient treatment, psychotic symptomatology, and parental history of BD.