The direct and indirect effects of lurasidone monotherapy on functional improvement among patients with bipolar depression: results from a randomized placebo-controlled trial.

Krithika Rajagopalan,Andrei Pikalov,Kathleen W Wyrwich,Antony Loebel,Elizabeth Dansie Bacci

doi:10.1186/s40345-016-0049-1

Abstract

BackgroundBipolar depression is characterized by depressive symptoms and impairment in many areas of functioning, including work, family, and social life. The objective of this study was to assess the independent, direct effect of lurasidone treatment on functioning improvement, and examine the indirect effect of lurasidone treatment on functioning improvement, mediated through improvements in depression symptoms.MethodsData from a 6-week placebo-controlled trial assessing the effect of lurasidone monotherapy versus placebo in patients with bipolar depression was used. Patient functioning was measured using the Sheehan disability scale (SDS). Descriptive statistics were used to assess the effect of lurasidone on improvement on the SDS total and domain scores (work/school, social, and family life), as well as number of days lost and unproductive due to symptoms. Path analyses evaluated the total effect (β1), as well as the indirect effect (β2×β3) and direct effect (β4) of lurasidone treatment on SDS total score change, using standardized beta path coefficients and baseline scores as covariates. The direct effect of treatment on SDS total score change and indirect effects accounting for mediation through depression improvement were examined for statistical significance and magnitude using MPlus.ResultsIn this 6-week trial (N = 485), change scores from baseline to 6-weeks were significantly larger for both lurasidone treatment dosage groups versus placebo on the SDS total and all three SDS domain scores (p < 0.05). Through path analyses, lurasidone treatment predicted improvement in depression (β2 = −0.33, p = 0.009), subsequently predicting improvement in functional impairment (β3 = 0.70, p < 0.001; indirect effect = −0.23). The direct effect was of medium magnitude (β4 = −0.17, p = 0.04), indicating lurasidone had a significant and direct effect on improvement in functional impairment, after accounting for depression improvement.ConclusionsResults demonstrated statistically significant improvement in functioning among patients on lurasidone monotherapy compared to placebo. Improvement in functioning among patients on lurasidone was largely mediated through a reduction in depression symptoms, but lurasidone also had a medium and statistically significant independent direct effect in improving functioning.

Highlights

Bipolar depression is characterized by depressive symptoms and impairment in many areas of functioning, including work, family, and social life
Change scores were significantly larger for both lurasidone dosage groups versus placebo on the Sheehan disability scale (SDS) total and all three SDS domain scores
The current analysis extends these findings by assessing if improvement in functional impairment (SDS) due to lurasidone treatment was independent of improvement in bipolar depression symptoms (MADRS)

Summary

Introduction

Bipolar depression is characterized by depressive symptoms and impairment in many areas of functioning, including work, family, and social life. Bipolar disorder is a chronic and debilitating mental illness characterized by recurrent episodes of hypomania, mania, and depressive symptoms (Goodwin and Jamison 2007). It is ranked by the World Health Organization as one of the top 20 causes of disability worldwide (Vos et al 2012). Since clinician-reported measures often do not capture treatment impact on functional status, activities of daily living, or quality of life, all of which are areas that are important in the context of functional impairment for patients (Kessler et al 2006; Miklowitz 2011; Harvey 2011; Greer et al 2010), recent emphasis has been placed on patient-reported outcome measures to complement symptomatic assessments in this population (Rosa et al 2010). Some argue that patient-reported measures of psychosocial functioning that reflect how a patient feels or functions are more meaningful outcomes than clinician-reported measures of symptomatic remission (Keck 2004)

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