Lithium treatment after electroconvulsive therapy in bipolar disorder: A nationwide target trial emulation

ObjectivesElectroconvulsive Therapy (ECT) is an effective treatment for bipolar disorder, particularly in severe acute cases or for illness resistant to pharmacotherapy. However, the risk of relapse following ECT is high, necessitating intervention to reduce this risk. Based on findings from ECT studies in unipolar depression and its well-known mood-stabilizing properties, it is likely that lithium treatment may reduce the risk of relapse of bipolar disorder following ECT. Therefore, we conducted a target trial emulation using data from Danish nationwide registers to investigate whether lithium protects against relapse following ECT treatment of bipolar disorder. MethodsPatients discharged from their first psychiatric admission with a primary diagnosis of bipolar disorder between January 1, 2006, and June 1, 2024, who received at least six ECT treatments, were included. Follow-up began two weeks after discharge and continued until relapse, death, one year, or January 1, 2025. Patients were considered allocated to lithium treatment if they redeemed a prescription for lithium within the first two weeks after discharge from the index admission (ECT treatment). The outcome was time to relapse, defined by either psychiatric hospital admission or suicide. Cox proportional hazards regression, adjusted for potential confounders, was used to compare the outcome between patients allocated and not allocated to lithium treatment. ResultsAmong the 574 eligible patients (mean age 41.5 years, 61.3% women), 214 (37.3%) were allocated to lithium treatment and 360 (62.7%) were not allocated to lithium treatment. During follow-up, 56 patients (26.2%) in the lithium group and 135 patients (37.5%) in the non-lithium group experienced a relapse. Lithium treatment was associated with a substantially reduced risk of relapse (adjusted hazard rate ratio, 0.60, 95% CI=0.43-0.84). ConclusionLithium treatment after ECT may reduce the risk of relapse in patients with bipolar disorder. These findings should be followed up by a randomized controlled trial.