Tolerability, Safety, and Effectiveness of Two Years of Treatment with Lurasidone in Children and Adolescents with Bipolar Depression.

To evaluate long-term safety and effectiveness of lurasidone in children and adolescents with bipolar depression. Participants, ages 10-17 years, with bipolar depression, who completed 6 weeks of double-blind (DB) treatment with lurasidone or placebo were enrolled in a 2-year, open-label (OL) extension study of lurasidone (20-80 mg/d). The primary effectiveness measure was the Children's Depression Rating Scale, Revised (CDRS-R). A total of 306 participants entered the 2-year extension study; 195 (63.7%) completed 52 weeks, and 168 (54.9%) completed 104 weeks of treatment. For all participants entering the extension study, mean change in CDRS from OL baseline was -13.4 at week 52, and -16.4 at week 104 (-11.3 at last observation carried forward [LOCF]-endpoint). Overall, 31 participants (10.1%) discontinued due to an adverse event (AE); the three most common AEs were headache (23.9%), nausea (16.4%), and somnolence (9.8%). OL treatment with lurasidone was associated with few effects on metabolic parameters or prolactin. Mean change from DB baseline in weight was +4.25 kg at week 52 (vs. an expected weight gain of +3.76 kg), and +6.75 kg at week 104 (vs. an expected weight gain of +6.67 kg), based on the sex- and age-matched United States Center for Disease Control normative data. For youth with bipolar depression, up to 2 years of treatment with lurasidone was generally well tolerated, safe, and effective with relatively low rates of discontinuation due to AEs, minimal effects on weight, metabolic parameters or prolactin, and continued improvement in depressive symptoms. Clinical Trial Registration number: NCT01914393.