title: Effects on health-related quality of life in patients treated with lurasidone for bipolar depression: results from two placebo controlled bipolar depression trials.
abstract: Depressive symptoms associated with bipolar disorder negatively impact health-related quality of life (HRQoL). The efficacy of lurasidone in reducing depressive symptoms has been previously demonstrated. The objective of this study was to examine the direct and indirect effect (mediated through improvement in depression symptoms) of lurasidone in improving patient HRQoL.
  
  
  
  A secondary analysis of data was conducted of two 6-week, double-blind, placebo-controlled trials assessing the effect of lurasidone (lurasidone monotherapy [20-60 mg/day or 80-120 mg/day]; lurasidone adjunctive to lithium or valproate [20-120 mg/day]) in patients with bipolar depression. Patient HRQoL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). Depression symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). Analysis of covariance (ANCOVA) was used to estimate the effect of lurasidone on improvement in the Q-LES-Q SF percentage maximum score from baseline to 6 weeks. Path analysis was used to evaluate the total effect (β1), as well as the indirect (β2*β3) and direct (β4) effect of lurasidone on Q-LES-Q SF change through improvements in MADRS.
  
  
  
  A total of 340 and 485 patients from the monotherapy and adjunctive therapy, respectively, were included in the analysis. At 6-weeks, ANCOVA analyses demonstrated that lurasidone provided significant improvement in adjusted mean Q-LES-Q SF scores in comparison to placebo for monotherapy (22.9 and 22.7 vs. 15.2, both p < 0.01) and adjunctive therapy (23.1 vs. 17.9, p = 0.01). Path analyses indicated that lurasidone treatment predicted MADRS improvement (monotherapy: β2 = -0.44, p < 0.001; adjunctive therapy: β2 = -0.34, p = 0.003), which subsequently predicted improvement in Q-LES-Q SF (monotherapy: β3 = -0.73, p < 0.001; adjunctive therapy: β3 = -0.75, p < 0.001); however, the effect of lurasidone on improvement in Q-LES-Q SF was largely mediated by change in MADRS (monotherapy: β4 = 0.11, p = 0.13; adjunctive therapy: β4 = 0.02, p = 0.77).
  
  
  
  Lurasidone as a monotherapy and adjunctive to lithium or valproate is an effective treatment for improving HRQoL in patients with bipolar depression. However, improvement in HRQoL was not independent of improvement in depression, indicating that the effect of lurasidone on improving patient HRQoL may act through a reduction in depressive symptoms associated with bipolar disorder.
  
  
  
  Clinicaltrials.gov identifiers: NCT00868699 and NCT00868452 (both registered March 23, 2009).
authors.affiliation: Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
authors.forename: Krithika
authors.initials: K
authors.lastname: Rajagopalan
authors.affiliation: Evidera, Seattle, WA, USA. elizabeth.bacci@evidera.com.
authors.forename: Elizabeth Dansie
authors.initials: ED
authors.lastname: Bacci
authors.affiliation: Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
authors.forename: Daisy
authors.initials: D
authors.lastname: Ng-Mak
authors.affiliation: Evidera, Bethesda, MD, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Wyrwich
authors.affiliation: Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Pikalov
authors.affiliation: Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Loebel
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use; D000069056:Lurasidone Hydrochloride / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life / Q000523:psychology*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D014635:Valproic Acid; D000069056:Lurasidone Hydrochloride
keywords: Bipolar disorder; Depression; Drug therapy; Patient functioning; Quality of life enjoyment and satisfaction questionnaire