Extended-Release Lithium Sulfate in Adolescents with Bipolar Disorder: Results from a Longitudinal Prospective Cohort Study

<b><i>Objectives:</i></b> Bipolar disorder (BD) in adolescence often associates with risky conducts, nonsuicidal self-injury (NSSI), and suicidal ideation. Lithium salts represent the first-line choice for BD in youth to manage manic symptoms and prevent both manic and depressive relapses. Our study aimed to assess efficacy and tolerability of extended-release lithium sulfate (ERLS) in youths with BD. <b><i>Methods:</i></b> A longitudinal perspective intervention study was thus conducted on a single cohort of 36 patients with BD aged 12-17 years treated with ERLS and followed up for 1 year. ERLS was titrated up to reach optimal plasma concentrations during the 3 months before baseline visit (T0). Then, patients underwent five follow-up visits after 1, 2, 3, 5, and 11 months and were administered with a battery of self- and parent-rated questionnaires and interviews to evaluate, at each timepoint, ERLS-related side effects, manic and depressive symptoms, emotional dysregulation (ED), NSSI and suicidality, and aggressiveness. Regular clinical assessments were also conducted, as well as blood tests, urinalysis, and EKG. Regression models were applied to examine the time course of outcome variables. <b><i>Results:</i></b> Twenty-four patients completed the follow-up. Regressions showed a significant reduction of most dependent variables included in the models, including depressive symptoms (β = -0.0006; adj-p = 0.0007), aggressiveness (β = -0.0031; adj-p < 0.0001), ED (β = -0.0002; adj-p = 0.0497), and unstructured suicidal ideation (β = -0.0058; adj-p = 0.0340). Fine distal tremor, increased thirst, and diuresis were among the most frequently reported side effects. <b><i>Conclusions:</i></b> Findings from the present study support the use of ERLS as an effective and well-tolerated agent for the management of BD in youth, with a beneficial effect on associated severe symptoms, including NSSI and suicidality.