title: A randomized, double-blind, placebo-controlled trial to assess prevention of mood episodes with risperidone long-acting injectable in patients with bipolar I disorder.
abstract: The efficacy and safety of risperidone long-acting injectable (LAI) for preventing recurrence of mood episodes in patients with bipolar I disorder was evaluated in a randomized, placebo-controlled study. After a 12-week open-label period with risperidone LAI (n=560), patients who did not experience a recurrence entered an 18-month randomized, double-blind period with risperidone LAI (n=132) or placebo (n=135); a third treatment arm (n=131) was randomized to oral olanzapine (10 mg/day) for reference and exploratory comparisons. The primary efficacy endpoint was time to recurrence of any mood episode for risperidone LAI versus placebo in the double-blind period (Kaplan-Meier analysis). Additional efficacy endpoints included Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression. During the double-blind period, dosing was fixed at patients' final open-label dose (25 mg, 66% of patients; 37.5 mg, 31%; 50 mg, 4%). The primary outcome demonstrated a median time to mood episode recurrence of 198 day in the placebo arm, whereas the median was not reached in the risperidone LAI arm (p=0.057). Time to recurrence of any mood episode was significantly longer with risperidone LAI versus placebo (log-rank test stratified by region only, p=0.031); the difference was significant for time to recurrence of elevated mood episodes (p=0.005) but not depressive episodes (p=0.655). Significant improvement of manic symptoms and global condition versus placebo were observed for risperidone LAI, with no evidence of worsening of depression. In conclusion, risperidone LAI significantly delayed time to recurrence of elevated mood episodes, with a safety profile consistent with previous studies.
authors.affiliation: Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Villarroel 170, 12-0, Barcelona 08036, Spain. evieta@clinic.ub.es
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Stuart
authors.initials: S
authors.lastname: Montgomery
authors.forename: Ahmad Hatim
authors.initials: AH
authors.lastname: Sulaiman
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cordoba
authors.forename: Benedicte
authors.initials: B
authors.lastname: Huberlant
authors.forename: Lupe
authors.initials: L
authors.lastname: Martinez
authors.forename: Andreas
authors.initials: A
authors.lastname: Schreiner
mesh_terms: D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000209:etiology / Q000517:prevention & control*; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007267:Injections; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D055502:Secondary Prevention; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018967:Risperidone