Longitudinal Comparative Effectiveness of Bipolar Disorder Therapies

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.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1037352

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Christophe G Lambert

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of individuals with bipolar disorder enrolled with private insurers or with Medicare across the United States, as captured in the Truven Health Analytics MarketScan databases. The time period of data coverage is 2003-2016.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: Patient-Centered Outcomes Research Institute; Montana State University; National Alliance on Mental Illness Montana; CGStat LLC; Risk Benefit Statistics LLC; National Alliance on Mental Illness New Mexico; National Alliance on Mental Illness Westside Los Angeles
• Investigators: Principal Investigator: Christophe G Lambert, PhD, University of New Mexico Health Sciences Center

Publications and helpful links

General Publications

• Nestsiarovich A, Hurwitz NG, Nelson SJ, Crisanti AS, Kerner B, Kuntz MJ, Smith AN, Volesky E, Schroeter QL, DeShaw JL, Young SS, Obenchain RL, Krall RL, Jordan K, Fawcett J, Tohen M, Perkins DJ, Lambert CG. Systemic challenges in bipolar disorder management: A patient-centered approach. Bipolar Disord. 2017 Dec;19(8):676-688. doi: 10.1111/bdi.12547. Epub 2017 Sep 13.
• Nestsiarovich A, Mazurie AJ, Hurwitz NG, Kerner B, Nelson SJ, Crisanti AS, Tohen M, Krall RL, Perkins DJ, Lambert CG. Comprehensive comparison of monotherapies for psychiatric hospitalization risk in bipolar disorders. Bipolar Disord. 2018 Dec;20(8):761-771. doi: 10.1111/bdi.12665. Epub 2018 Jun 19.
• Nestsiarovich A, Kerner B, Mazurie AJ, Cannon DC, Hurwitz NG, Zhu Y, Nelson SJ, Oprea TI, Unruh ML, Crisanti AS, Tohen M, Perkins DJ, Lambert CG. Comparison of 71 bipolar disorder pharmacotherapies for kidney disorder risk: The potential hazards of polypharmacy. J Affect Disord. 2019 Jun 1;252:201-211. doi: 10.1016/j.jad.2019.04.009. Epub 2019 Apr 8.
• Kerner B, Crisanti AS, DeShaw JL, Ho JG, Jordan K, Krall RL, Kuntz MJ, Mazurie AJ, Nestsiarovich A, Perkins DJ, Schroeter QL, Smith AN, Tohen M, Volesky E, Zhu Y, Lambert CG. Preferences of Information Dissemination on Treatment for Bipolar Disorder: Patient-Centered Focus Group Study. JMIR Ment Health. 2019 Jun 25;6(6):e12848. doi: 10.2196/12848.
• Kumar P, Nestsiarovich A, Nelson SJ, Kerner B, Perkins DJ, Lambert CG. Imputation and characterization of uncoded self-harm in major mental illness using machine learning. J Am Med Inform Assoc. 2020 Jan 1;27(1):136-146. doi: 10.1093/jamia/ocz173.
• Nestsiarovich A, Kerner B, Mazurie AJ, Cannon DC, Hurwitz NG, Zhu Y, Nelson SJ, Oprea TI, Crisanti AS, Tohen M, Perkins DJ, Lambert CG. Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder. Psychoneuroendocrinology. 2020 Feb;112:104511. doi: 10.1016/j.psyneuen.2019.104511. Epub 2019 Nov 9.
• Nestsiarovich A, Kumar P, Lauve NR, Hurwitz NG, Mazurie AJ, Cannon DC, Zhu Y, Nelson SJ, Crisanti AS, Kerner B, Tohen M, Perkins DJ, Lambert CG. Using Machine Learning Imputed Outcomes to Assess Drug-Dependent Risk of Self-Harm in Patients with Bipolar Disorder: A Comparative Effectiveness Study. JMIR Ment Health. 2021 Apr 21;8(4):e24522. doi: 10.2196/24522.

Helpful Links

• Announcement of PCORI project award.
• Results summary

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: August 30, 2016
• First Submitted That Met QC Criteria: September 7, 2016
• First Posted (Estimated): September 8, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Agents; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Antidepressive Agents, Tricyclic; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inducers; Serotonin 5-HT3 Receptor Antagonists; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Cytochrome P-450 CYP3A Inducers; Dopamine Uptake Inhibitors; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Adrenergic alpha-Antagonists; Anti-Dyskinesia Agents; Adrenergic alpha-2 Receptor Antagonists; Cytochrome P-450 CYP2C19 Inhibitors; GABA Antagonists; Selective Serotonin Reuptake Inhibitors; Olanzapine; Aripiprazole; Sertraline; Duloxetine Hydrochloride; Citalopram; Paroxetine; Lamotrigine; Paliperidone Palmitate; Bupropion; Valproic Acid; Quetiapine Fumarate; Risperidone; Ziprasidone; Lithium Carbonate; Desvenlafaxine Succinate; Venlafaxine Hydrochloride; Mirtazapine; Asenapine; Fluoxetine; Haloperidol; Carbamazepine; Oxcarbazepine; Lurasidone Hydrochloride; Clozapine; Perphenazine; Fluvoxamine; Doxepin; Vilazodone Hydrochloride; Escitalopram
• Other Study ID Numbers: 16-243; CER-1507-31607 (Other Grant/Funding Number: PCORI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This retrospective observational study makes use of MarketScan individual level patient data from Truven Health Analytics. The license terms for data access prohibit public dissemination of individual level patient data. The investigators will, however, make openly available the queries and analytic procedures required to reproduce the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No