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Mental Health

Association between Maintenance Dose of Mood Stabilizer and Relapse Risk in Patients with Incident Bipolar Disorder in Korea: A Nationwide, Register-based Cohort Study Sunghyuk Kang* Sunghyuk Kang Sun Jae Jung

Background: It is recommended to treat the maintenance phase of bipolar disorder with the minimal effective dose of mood stabilizers, but evidence on a quantitative dosing strategy is lacking. We aimed to estimate the association between relative maintenance doses of mood stabilizers compared to the dose during the first admission and the risk of relapse in patients with incident bipolar disorder.

Methods: This retrospective cohort study included patients with incident bipolar disorder between 2002 and 2020, identified from the National Health Information Database of South Korea. Patients who were hospitalized for incident bipolar disorder and used mood stabilizers ≥0.1 defined daily doses during the first admission were included. After discharge from the first admission, relative maintenance doses of mood stabilizers were calculated using the dose during the first admission, representing dose in acute phase, as the denominator. Relapse was defined as rehospitalization for mood disorders (ICD-10; F30–39). The hazard ratio (HR) of relapse was estimated using extended Cox regression, with time-varying exposure of relative mood stabilizer dose.

Results: Out of 10,542 patients (mean age=37.0 years; 51.2% women) admitted for incident bipolar disorder, 50.4% relapsed. The risk of relapse did not vary with a relative maintenance dose of mood stabilizers >60%, but for doses lower than that, the risk of relapse increased as the dose was reduced (reference=80–100%; 0–20%, HR=1.66 [95% CI: 1.39–1.99]; 20–40%, 1.29 [1.13–1.47]; 40–60%, 1.22 [1.08–1.38]; 60–80%, 1.05 [0.93–1.19]; >100%, 1.07 [0.94–1.22]).

Conclusion: Among patients with incident bipolar disorder, the risk of relapse was elevated with a substantial reduction in maintenance doses of mood stabilizers compared to the acute dose. Physicians should consider prescribing sufficient mood stabilizer doses to prevent relapse in patients with bipolar disorder.