Longitudinal Comparative Effectiveness of Bipolar Disorder Therapies

Study Overview
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Brief Summary
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The objective of this retrospective observational study is to compare commonly prescribed bipolar disorder medications for their impact on: (1) hospitalization; (2) suicide attempts and self-harm; and (3) risk of drug-induced adverse effects such as kidney disease and diabetes mellitus. In addition, the investigators will examine heterogeneity of treatment effect by co-morbidity within pediatric, adult, and elderly sub-populations. Patient focus groups are convened to elicit additional questions and provide feedback on results.

Detailed Description
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Funded by PCORI, the objective of this retrospective observational study is to perform several safety and effectiveness comparisons on commonly prescribed bipolar disorder medications, engaging patient focus groups in generating additional questions and interpreting results. The study will be a retrospective cohort study conducted with administrative claims data from the Truven MarketScan Commerical Claims and Encounters and Medicare database from 2010-2016. The database contains approximately 140 million patients within the US population in every state and nearly every county in the nation, across all ages, ethnicities and socioeconomic categories, including privately insured, and Medicare patients. The study will focus on approximately one million patients with two or more diagnoses of bipolar disorder in the claims records according to ICD-9 and/or ICD-10 coding. The treatments that will be compared are lithium carbonate; first generation antipsychotics: haloperidol and perphenazine; second generation antipsychotics: clozapine, risperidone, olanzapine, aripiprazole, quetiapine, ziprasidone, asenapine, lurasidone, and paliperidone; mood stabilizing anticonvulsants: valproate, lamotrigine, carbamazepine, and oxcarbazepine; antidepressants: mirtazapine, bupropion, desvenlafaxine, duloxetine, venlafaxine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vilazodone, and doxepin. The investigators will perform cross-sectional and survival based analysis using regression, propensity scoring, and local control to perform bias-corrected comparisons of the above treatments for for their impact on: (1) hospitalization; (2) suicide attempts and self-harm; and (3) risk of drug-induced adverse effects such as kidney disease and diabetes mellitus. In addition, the investigators will examine heterogeneity of treatment effect by co-morbidity within pediatric, adult, and elderly sub-populations.

Official Title
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Longitudinal Comparative Effectiveness of Bipolar Disorder Therapies

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Lithium Carbonate
* Drug: Lamotrigine
* Drug: Valproic Acid
* Drug: Oxcarbazepine
* Drug: Carbamazepine
* Drug: Ziprasidone
* Drug: Risperidone
* Drug: Quetiapine
* Drug: Olanzapine
* Drug: Aripiprazole
* Drug: Fluoxetine / Olanzapine
* Drug: Haloperidol
* Drug: Perphenazine
* Drug: Clozapine
* Drug: Asenapine
* Drug: Lurasidone
* Drug: Paliperidone
* Drug: Mirtazapine
* Drug: Bupropion
* Drug: Desvenlafaxine
* Drug: Duloxetine
* Drug: Venlafaxine
* Drug: Citalopram
* Drug: Escitalopram
* Drug: Fluoxetine
* Drug: Fluvoxamine
* Drug: Paroxetine
* Drug: Sertraline
* Drug: Vilazodone
* Drug: Doxepin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Two or more instances of bipolar disorder diagnoses within administrative claims records Exclusion Criteria: Patients with less than 1 year of history in the database
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lithium Carbonate|Exposure to all dosages and delivery forms.|
|Drug: Lamotrigine|Exposure to all dosages and delivery forms.|
|Drug: Valproic Acid|Exposure to all dosages and delivery forms.|
|Drug: Oxcarbazepine|Exposure to all dosages and delivery forms.|
|Drug: Carbamazepine|Exposure to all dosages and delivery forms.|
|Drug: Ziprasidone|Exposure to all dosages and delivery forms.|
|Drug: Risperidone|Exposure to all dosages and delivery forms.|
|Drug: Quetiapine|Exposure to all dosages and delivery forms.|
|Drug: Olanzapine|Exposure to all dosages and delivery forms.|
|Drug: Aripiprazole|Exposure to all dosages and delivery forms.|
|Drug: Fluoxetine / Olanzapine|Exposure to all dosages and delivery forms.|
|Drug: Haloperidol|Exposure to all dosages and delivery forms.|
|Drug: Perphenazine|Exposure to all dosages and delivery forms.|
|Drug: Clozapine|Exposure to all dosages and delivery forms.|
|Drug: Asenapine|Exposure to all dosages and delivery forms.|
|Drug: Lurasidone|Exposure to all dosages and delivery forms.|
|Drug: Paliperidone|Exposure to all dosages and delivery forms.|
|Drug: Mirtazapine|Exposure to all dosages and delivery forms.|
|Drug: Bupropion|Exposure to all dosages and delivery forms.|
|Drug: Desvenlafaxine|Exposure to all dosages and delivery forms.|
|Drug: Duloxetine|Exposure to all dosages and delivery forms.|
|Drug: Venlafaxine|Exposure to all dosages and delivery forms.|
|Drug: Citalopram|Exposure to all dosages and delivery forms.|
|Drug: Escitalopram|Exposure to all dosages and delivery forms.|
|Drug: Fluoxetine|Exposure to all dosages and delivery forms.|
|Drug: Fluvoxamine|Exposure to all dosages and delivery forms.|
|Drug: Paroxetine|Exposure to all dosages and delivery forms.|
|Drug: Sertraline|Exposure to all dosages and delivery forms.|
|Drug: Vilazodone|Exposure to all dosages and delivery forms.|
|Drug: Doxepin|Exposure to all dosages and delivery forms.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of hospitalization | For each treatment, assess the risk of rehospitalization within 30-days after hospitalization for a mood episode. For each treatment, assess the cumulative incidence of hospitalization for a mood episode any time after commencing treatment, accounting for the competing risk of ending treatment. | 0-7 years | 
| Risk of suicide and self-harm | For each treatment, assess the cumulative risk of a second suicide or self-harm event after diagnosis of a first event, accounting for the competing risk of ending treatment. Self-harm includes injuries of unknown intent. | 0-7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney disease | For each treatment, assess time to first instance of renal condition. | 0-7 years | 
| Diabetes mellitus | For each treatment, assess time to diagnosis of diabetes mellitus | 0-7 years |