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

Melissa P DelBello, Michael Tocco, Andrei Pikalov, Ling Deng, Robert Goldman, Melissa P DelBello, Michael Tocco, Andrei Pikalov, Ling Deng, Robert Goldman

Abstract

Objectives: To evaluate long-term safety and effectiveness of lurasidone in children and adolescents with bipolar depression. Methods: 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). Results: 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. Conclusions: 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.

Keywords: adolescents; bipolar disorder; children; depressive disorder; lurasidone; second-generation antipsychotic.

Figures

FIG. 1.
FIG. 1.
Participant disposition.
FIG. 2.
FIG. 2.
Change from DB baseline in weight and BMI: actual versus expected. BMI, body mass index; DB, double-blind.
FIG. 3.
FIG. 3.
Change from DB baseline in severity scores (OC analyses) (A). CDRS-R total score (B). CGI-BP-S depression score. CDRS-R, Children's Depression Rating Scale, Revised; CGI-BP-S, Clinical Global Impression-Bipolar Version, Severity; DB, double-blind; OC, observed case analysis.
FIG. 4.
FIG. 4.
Secondary efficacy outcomes during OL treatment with lurasidone (A). Change from DB baseline in CGAS and PQ-LES-Q scores OC, observed case analysis; (B). Response and remission during OL treatment with lurasidone. CGAS, Children's Global Assessment Scale; DB, double-blind; OC, observed case analysis; OL, open-label; PQ-LES-Q, Pediatric Quality-of-Life Enjoyment and Satisfaction Questionnaire.

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