Co-morbid Disruptive Behavior Disorder and Aggression Predict Functional Outcomes and Differential Response to Risperidone Versus Divalproex in Pharmacotherapy for Pediatric Bipolar Disorder

Amy E West,Mani N Pavuluri,Sally M Weinstein,Christine I Celio,David Henry

doi:10.1089/cap.2010.0140

Abstract

Co-morbid diagnoses, such as disruptive behavior disorders (DBDs) and high levels of aggression, are extremely common among youth with pediatric bipolar disorder (PBD) and may interfere with treatment response; however, they have rarely been examined as predictors of response to pharmacotherapy. The current study examines co-morbid DBD and aggression prospectively as predictors of pharmacotherapy outcome, as well as potential moderators of response to a specific medication (risperidone vs. divalproex), among children with PBD. Data are from a prospective 6-week double-blind, placebo-controlled, randomized outpatient medication treatment trial of risperidone versus divalproex for manic episodes in 65 children 8-18 with PBD. Outcome measures were administered at pretest, post-test, and weekly during the 6 weeks of treatment. Mixed-effects regression models were used to examine pharmacotherapy response. Results indicated that youth with co-morbid DBD experienced greater improvement in manic symptoms in response to risperidone versus divalproex, whereas youth with non-co-morbid DBD experienced similar trajectories of symptom improvement in both medication groups. In addition, the non-DBD group experienced greater improvement in global functioning over time as compared with youth with co-morbid-DBD, and this gap increased over the course of treatment. Results also indicated that high-aggression youth experienced worse global functioning by end treatment versus low-aggression youth. In conclusion, a co-morbid diagnosis of DBD and/or high levels of aggressive symptoms in youth with PBD may be important clinical predictors of variation in treatment response to pharmacotherapy. These findings may help researchers and clinicians develop tailored treatment approaches that optimize symptom and functional outcomes.

Highlights

Understanding the predictors of pharmacotherapy response in pediatric bipolar disorder (PBD) is integral to developing more personalized and effective interventions
In terms of global functioning, consistent with our hypothesis, youth with co-morbid disruptive behavior disorders (DBDs) demonstrated worse outcomes overall compared with the non-co-morbid DBD group. These results indicate that youth with PBD with co-morbid DBD may experience greater improvements in mania symptoms and global functioning in response to risperidone compared with divalproex, whereas youth with PBD without co-morbid DBD may benefit from either medication
Pharmacotherapy treatment with divalproex or risperidone resulted in improved symptoms and functional outcomes across youth with a range of aggressive behavior, youth with PBD who demonstrate higher levels of aggression at baseline may show attenuated response compared with their low-aggression peers in terms of global functioning post-treatment

Summary

Introduction

Understanding the predictors of pharmacotherapy response in pediatric bipolar disorder (PBD) is integral to developing more personalized and effective interventions. Youth with PBD frequently present with a heterogeneous clinical picture, including co-morbid diagnoses and considerable levels of aggression, which can camouflage the primary diagnosis and complicate treatment. The objective of this study is to examine how salient clinical factors, including co-morbid disruptive behavior disorders (DBDs) and high levels of aggressive features, may influence response to pharmacotherapy in PBD. Findings indicate that >40% of PBD youth have a poor response to pharmacotherapy, with low rates of remission and high rates of recurrence (Emslie et al 2003; Geller et al 2008; Birmaher et al 2009). Research has increasingly focused on understanding the factors that may predict outcome to pharmacotherapy among youth with PBD to enhance treatment outcomes. Albeit mixed, suggest that clinical features such as symptom severity and co-morbid diagnoses may predict treatment nonresponse (Masi et al 2004)

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