Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study

Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD.