Monotherapy with Mood Stabilizers versus Atypical Antipsychotics for the Treatment of Bipolar Disorder in Children and Adolescents

Transcription

1 Monotherapy with Mood Stabilizers versus Atypical Antipsychotics for the Treatment of Bipolar Disorder in Children and Adolescents Mehta S 1,2, Patel A 2, Aparasu RR 2, Perez MO 3, Chen H 2 Affiliations: 1. Pharmerit North America, LLC., Bethesda, MD 2. College of Pharmacy, University of Houston, Houston, TX 3. Legacy Community Health Services, Houston, TX ISPOR 17 th Annual International Meeting, Washington DC, June 4, 2012

2 Pediatric Bipolar Disorder (PBD) PBD Is more severe than adult bipolar disorder Has rapid cycling ( 4 episodes/year) Has a high rate of psychiatric hospitalizations Results in major burden: Poor academic performance Deteriorated relationships Increased risk of suicide PBD treatment Mood stabilizers Atypical antipsychotics 2

3 Statement of Problem Limited comparative effectiveness research (CER) on mood stabilizers and atypical antipsychotics in PBD No CER study in PBD has considered Long-term (i.e. 2 months) symptom relief Adherence and persistence s impact on outcomes Time to hospitalization 3

4 Study Objectives Objective 1: Utilization pattern Objective 2: Adherence and persistence Objective 3: Time to first bipolar related hospitalization 4

5 Study Design & Data Source Retrospective longitudinal cohort study Medicaid Analytic extract (MAX) TX, NY, CA and IL Outpatients (6-18 years) with BD ICD-9-CM diagnosis and no schizophrenia or epilepsy diagnosis 5

6 Cohort Identification Index date - date of the first Rx filled either for mood stabilizer or atypical antipsychotic monotherapy during exposure period. Wash-out Follow-up 6 months 12 months Jan 2003 July 2003 Dec 2006 Exposure Period Dec 2007 Index date 6

7 Statistical Analysis Adherence (Medication Possession Ratio [MPR]) Descriptive statistics and T-test Multivariate linear regression analysis Persistence Time to discontinuation Time to augmentation Hospitalization Survival analysis Kaplan-Meier (KM) Curve Cox proportional hazards regression (CPHR) model 7

8 Statistical Analysis All Multivariate analyses - Heckman s Two-Stage Selection Correction Estimation Control for selection bias due to physician prescribing preference Two-stage analysis 1. Logistic Regression Dependent variable Index medication Independent variables - demographic characteristics, comorbidities and physician preference. Estimate Inverse mills ratio 2. a). CPHR for persistence and hospitalization b). Multiple linear regression for adherence 8

9 Covariates Demographic Characteristics Age at index date (6 to 12 years and years) Gender Race (Whites, Blacks and Others) State (TX, CA, IL and NY) Presence in foster care (Yes/No) Psychotherapy (Yes/No) Comorbidities ADHD, Oppositional defiant disorder, Conduct disorder, Anxiety disorders, Substance use disorder 9

10 Objective 1: Utilization Pattern Total no. of Patients = 4,173, 078 Total no. of Patients with PBD = 110,253 Patients initiated on Monotherapy = 8,424 Mood Stabilizers 3026 (35.92%) Atypical Antipsychotics 5938 (64.08%) 10

11 Objective 1: Utilization Pattern Monotherapy initiation in PBD 36% - Mood stabilizers Lithium - Narrow therapeutic window Hepatotoxicity associated with anticonvulsants Diligent monitoring required 64% - Atypical antipsychotics More speedy response Convenient to use 11

12 Objective 2: Adherence (MPR) Variable Mood Stabilizers Atypical Antipsychotics P-value (T-test) Mean (±SD) MPR 0.77± ± Multiple Linear Regression (Using Heckman Correction) After controlling for physician preference and patient characteristics, no difference in mean MPR for patients who initiated mood stabilizers vs atypical antipsychotics 12

13 Objective 2: Time to Discontinuation Log Rank P-value =

14 Objective 2: Time to Discontinuation Variables Hazard Ratio (95% CI) P-value Index Medication Mood Stabilizer Atypical Antipsychotic Age Children (6-12 years) Adolescents (13-17 years) Race Others Whites Blacks Foster Care No Yes Psychotherapy No Yes 1.04 ( ) ( )* 0.014* 0.86 ( )* 1.21 ( )* 0.016* 0.001* 0.68 ( )* < * 1.11 ( )* 0.040* Inverse Mills Ratio 1.41 ( )* * 14

15 Objective 2: Time to Augmentation Atypical Antipsychotics Mood Stabilizers Log Rank P-value <

16 Objective 2: Time to Augmentation Variables Hazard Ratio (95% CI) P-value Index Medication Mood Stabilizer Atypical Antipsychotic 0.71 ( )* 0.002* Age Children (6-12 years) Adolescents (13-17 years) 0.69 ( )* 0.009* State Texas California Illinois New York 0.63 ( )* 0.73 ( )* 0.80 ( ) 0.004* 0.018* Foster Care No Yes 2.00 ( )* < * Inverse Mills Ratio 1.52 ( )* 0.044* 16

17 Objective 3: Time to Hospitalization Log Rank P-value =

18 Objective 3: Time to Hospitalization Variables Hazard Ratio (95% CI) P-value Index Medication Mood Stabilizer Atypical Antipsychotic Gender Male Female Oppositional Defiant Disorder No Yes 1.26 ( ) ( )* 0.013* 1.62 ( )* 0.038* 18

19 Strengths and Limitations Strengths Study design and analytical approach Long term longitudinal outcomes Only new users included - No prevalence bias Limitations Dose- and within-class augmentation not considered 19

20 Conclusion Atypical antipsychotic monotherapy predominantly prescribed for PBD as compared to mood stabilizers Both classes comparable in Adherence Preventing bipolar-related hospitalizations Atypical antipsychotics slightly better than mood stabilizers in time to augmentation Comparative risk of adverse drug events needs to be assessed 20

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