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IIR 10-314 – HSR Study

IIR 10-314
Spatiotemporal Spread of Newer Antipsychotics for Bipolar Disorder and PTSD
Mark S Bauer, MD
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, MA
Funding Period: July 2011 - June 2014
Previous research indicates that patient, provider, and health system characteristics are important factors in the adoption of healthcare innovations, including new prescribing patterns and/or medication utilization. We propose that interventions to enhance evidence-based prescribing can be focused for maximal effectiveness and efficiency, and that doing so depends on knowledge of the flow of information and influence among providers working within a specific organizational context with specific types of patients.

Such knowledge requires, specifically: (a) early identification of change in prescribing behavior (surveillance), (b) identification of characteristics of prescribers with a propensity to early adoption while controlling for confounding factors (including patient characteristics), and (c) identification of specific methods of intervention by determining the relative importance of social vs. administrative factors in a provider's decision to prescribe. Study of the emerging use of second generation antipsychotics (SGAs) for bipolar disorder and PTSD in the 2000s provided an opportunity to investigate these issues.

This study focused on (a) conducting basic pharmacoepidemiologic research to identify patterns of use of SGAs for bipolar disorder and PTSD, and (b) identifying spatiotemporal clusters (STCs) that describe the spread of prescribing SGAs for these disorders. Focusing on SGAs in bipolar disorder took advantage of several discrete events in 2004-new FDA indications for bipolar disorder-that anchored the investigation of diffusion. PTSD provided an important complementary disorder by which to study innovation spread since SGAs have become widely used for PTSD-though without FDA indications.

The study Specific Aims were: (1) to identify and characterize the dynamics of STCs of early adopter providers prescribing SGAs for bipolar disorder including to evaluate: (1a) the demographic characteristics of prescribers; (1b) the demographic characteristics of the patients who receive prescriptions, and (1c) the structural and cultural organizational characteristics at the VISN, VAMC, and CBOC levels within which the prescribing occurs; and (2) to characterize the robustness of early adopter prescriber profiles by: (2a) determining the consistency of early adopter characteristics across SGAs and (2b) determining whether the same characteristics that identify early adopters for bipolar disorder also identify early adopters for PTSD; and (3) to develop an integrated model that characterizes the relative strength of diffusion-based versus organizational factors in prescribers' likelihood of adopting SGAs for bipolar disorder.

We employed fundamental pharmacoepidemiologic methods to describe the spread of SGAs for bipolar disorder and PTSD, and then utilized geographic information systems (GIS) methods to identify STCs for these disorders. We worked with national VHA data from Decision Support System, Personnel and Accounting Integrated Dataset, and related VA databases to identify STCs of early adopter providers prescribing SGAs for bipolar disorder, and within these STCs to evaluate demographic characteristics of prescribers and patients who received prescriptions, along with the structural and cultural organizational characteristics at VISN, VAMC, and CBOC levels within which the prescribing occurred. Finally, we developed an integrated model that characterized the relative strength of diffusion-based versus organizational factors in prescribers' likelihood of adopting SGAs for bipolar disorder. We hypothesized that both geographic factors, consistent with classic diffusion theory, and organizational factors, as articulated in more recent applications of diffusion theory to dissemination within healthcare organizations, shaped SGA spread and, therefore, identified opportunities for intervention.

Our pharmacoepidemiologic studies indicated that the number of subjects with bipolar disorder using SGAs nearly doubled between 2003 and 2010, resulting in an average increase in SGA use of about 7% per year. Subjects with prior psychiatric hospitalizations, psychotic features and a sleep disorder diagnosis were more likely to initiate SGA treatment, although SGA initiation increased over time among those with milder symptoms. Subjects located in the southern region of the country were more likely to initiate SGA treatment. Most medical comorbidities were only modestly associated with SGA initiation as a whole, although significant findings emerged for individual SGAs.

Further, among 732,085 Veterans with PTSD, 27.6% received an intentional trial of an SGA in 2003-2010. The annual number treated with SGAs almost doubled (45,268 to 84,197), despite decreasing prescribing rates (28.6% to 21.5%) in this rapidly expanding population. In multivariate analyses, strongest clinical associations were with prior diagnosis of depression, substance use disorders, and other anxiety disorders as well as cardiovascular risk factors. Veterans previously deployed to Iraq/Afghanistan had lower likelihood of SGA receipt. Substantial regional differences were demonstrated (South>Northeast; Midwest and West

STC analyses revealed discrete clusters of early prescribing of the SGA aripiprazole for bipolar disorder, with counts of new prescribers (raw numbers) centering in New England and the Midwest. Utilizing rates, somewhat different clusters emerged, as expected, with two clusters identified in the Midwest and the Southwest. Hierarchical linear analyses to identify provider factors associated with early prescribing, while controlling for patient factors, are underway at the time of this writing. Complementary analyses are also underway to determine whether social-spatial or administrative factors predominate in influencing prescribers by investigating CBOC vs. parent VAMC differences in prescribing. At present, analyses indicate that there is a strong relationship between VAMC and CBOC without strong impact of hypothesized geographic factors (i.e., distance between sites, same/different state of sites). However, these analyses are still ongoing so conclusions cannot yet be drawn.

In addition to the specific importance to the VA of understanding the spread of these expensive medications for two high-priority disorders , this investigation represents two methodologic advances that are applicable beyond these specific disorders and medications: (a) the linking of prescriber data to prescription, patient, and facility data to identify correlates of prescriber behavior after controlling for patient and facility characteristics, and (b) the integrated analysis of innovation spread through both spatial-social and administrative space. This knowledge will both guide the targeted development and implementation of provider behavior change strategies for the VHA, and will test and refine the diffusion-based theory for applying these techniques within and beyond our healthcare system. What is notable at this point in time is that there is no evidence of "runaway" prescribing of SGAs in these populations. Rather, the rates of SGA prescribing have declined somewhat for both bipolar disorder and PTSD. The increase in number of prescription is driven primarily by increase in the population, most dramatically for PTSD..

Moreover, STCs can be used as surveillance methods in close-to-real-time to detect trends in prescribing and to delineate their "contagion routes" through social-spatial and administrative space. Further, since academic detailing is costly, identifying STCs of early prescribing can segment the "market" for more effective deployment of academic detailing.

External Links for this Project

NIH Reporter

Grant Number: I01HX000520-01

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Journal Articles

  1. Bauer MS, Miller CJ, Li M, Bajor LA, Lee A. A population-based study of the comparative effectiveness of second-generation antipsychotics vs older antimanic agents in bipolar disorder. Bipolar disorders. 2016 Sep 1; 18(6):481-489. [view]
  2. Gören JL, Meterko M, Williams S, Young GJ, Baker E, Chou CH, Kilbourne AM, Bauer MS. Antipsychotic prescribing pathways, polypharmacy, and clozapine use in treatment of schizophrenia. Psychiatric services (Washington, D.C.). 2013 Jun 1; 64(6):527-33. [view]
  3. Mohr DC, Bauer MS, Penfold RB. Changes in VA psychiatrists' attitudes about work environment and turnover during mental health service enhancement. Psychiatric services (Washington, D.C.). 2013 Jun 1; 64(6):563-9. [view]
  4. Miller CJ, Grogan-Kaylor A, Perron BE, Kilbourne AM, Woltmann E, Bauer MS. Collaborative chronic care models for mental health conditions: cumulative meta-analysis and metaregression to guide future research and implementation. Medical care. 2013 Oct 1; 51(10):922-30. [view]
  5. Woltmann E, Grogan-Kaylor A, Perron B, Georges H, Kilbourne AM, Bauer MS. Comparative effectiveness of collaborative chronic care models for mental health conditions across primary, specialty, and behavioral health care settings: systematic review and meta-analysis. The American journal of psychiatry. 2012 Aug 1; 169(8):790-804. [view]
  6. Bauer MS, Bernett AC, Willens DE. Effectiveness-implementation hybrid designs: implications for quality improvement science. Implementation science : IS. 2013 Apr 19; 8(supl1):s2. [view]
  7. Miller C, Bauer MS. Excess mortality in bipolar disorders. Current psychiatry reports. 2014 Nov 1; 16(11):499. [view]
  8. Ellison ML, Belanger LK, Niles BL, Evans LC, Bauer MS. Explication and Definition of Mental Health Recovery: A Systematic Review. Administration and policy in mental health. 2018 Jan 1; 45(1):91-102. [view]
  9. Penfold RB, Kilbourne AM, Mohr DC, Lai Z, Seibert MN, Bauer MS. Heterogeneity in aripiprazole diffusion for bipolar disorder treatment in the Veterans Health Administration. Psychiatric services (Washington, D.C.). 2012 Dec 1; 63(12):1178-85. [view]
  10. Kilbourne AM, Williams M, Bauer MS, Arean P. Implementation Research: Reducing the Research-to-Practice Gap in Depression Treatment. Depression research and treatment. 2012 Dec 26; 2012(1):476027. [view]
  11. Kilbourne AM, Goodrich DE, Nord KM, Van Poppelen C, Kyle J, Bauer MS, Waxmonsky JA, Lai Z, Kim HM, Eisenberg D, Thomas MR. Long-Term Clinical Outcomes from a Randomized Controlled Trial of Two Implementation Strategies to Promote Collaborative Care Attendance in Community Practices. Administration and policy in mental health. 2015 Sep 1; 42(5):642-53. [view]
  12. Khatana SA, Kane J, Taveira TH, Bauer MS, Wu WC. Monitoring and prevalence rates of metabolic syndrome in military veterans with serious mental illness. PLoS ONE. 2011 Apr 26; 6(4):e19298. [view]
  13. Semla TP, Lee A, Gurrera R, Bajor L, Li M, Miller DR, Smith EG, Wang C, Wan Y, Kazis LE, Bauer MS. Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia. Journal of the American Geriatrics Society. 2017 Aug 1; 65(8):1789-1795. [view]
  14. Bauer MS, Lee A, Li M, Bajor L, Rasmusson A, Kazis LE. Off-label use of second generation antipsychotics for post-traumatic stress disorder in the Department of Veterans Affairs: time trends and sociodemographic, comorbidity, and regional correlates. Pharmacoepidemiology and drug safety. 2014 Jan 1; 23(1):77-86. [view]
  15. Miller CJ, Li M, Penfold RB, Lee AF, Smith EG, Osser DN, Bajor L, Bauer MS. Patterns of initiation of second generation antipsychotics for bipolar disorder: a month-by-month analysis of provider behavior. BMC psychiatry. 2014 Nov 30; 14(1):339. [view]
  16. Bauer MS, Leader D, Un H, Lai Z, Kilbourne AM. Primary care and behavioral health practice size: the challenge for health care reform. Medical care. 2012 Oct 1; 50(10):843-8. [view]
  17. Kilbourne AM, Neumann MS, Waxmonsky J, Bauer MS, Kim HM, Pincus HA, Thomas M. Public-academic partnerships: evidence-based implementation: the role of sustained community-based practice and research partnerships. Psychiatric services (Washington, D.C.). 2012 Mar 1; 63(3):205-7. [view]
  18. Miller CJ, Abraham KM, Bajor LA, Lai Z, Kim HM, Nord KM, Goodrich DE, Bauer MS, Kilbourne AM. Quality of life among patients with bipolar disorder in primary care versus community mental health settings. Journal of affective disorders. 2013 Mar 20; 146(1):100-5. [view]
  19. Kilbourne AM, Nord KM, Kyle J, Van Poppelen C, Goodrich DE, Kim HM, Eisenberg D, Un H, Bauer MS. Randomized controlled trial of a health plan-level mood disorders psychosocial intervention for solo or small practices. BMC psychology. 2014 Nov 13; 2(1):48. [view]
  20. Penfold RB, Burgess JF, Lee AF, Li M, Miller CJ, Nealon Seibert M, Semla TP, Mohr DC, Kazis LE, Bauer MS. Space-Time Cluster Analysis to Detect Innovative Clinical Practices: A Case Study of Aripiprazole in the Department of Veterans Affairs. Health services research. 2018 Feb 1; 53(1):214-235. [view]
Journal Other

  1. Janney CA, Bauer MS, Kilbourne AM. Self-management and bipolar disorder--a clinician's guide to the literature 2011-2014. Current psychiatry reports. 2014 Sep 1; 16(9):485. [view]
VA Cyberseminars

  1. Bauer MS, Ripley C, Penfold R. Using Spatial Analysis Tools in Implementation Science - QUERI Implementation Research. [Cyberseminar]. 2012 Sep 13. [view]
Conference Presentations

  1. Sayer NA, Rosen CS, Nugent S, Kehle-Forbes SM, Chard K, Bernardy NC, Schnurr P, Orazem R, Mohr D. A Preliminary Look at Use of PE and CPT in VHA Specialty Outpatient PTSD Programs. Paper presented at: VA HSR&D / QUERI National Meeting; 2015 Jul 9; Philadelphia, PA. [view]
  2. Bauer MS, Penfold R, Kazis LE, Lee A, Cowper-Ripley D, Fortney JC. Geographic information systems (GIS) in health services research. Presented at: VA HSR&D / QUERI National Meeting; 2012 Jul 17; National Harbor, MD. [view]
  3. Mohr DC, Burgess JF, Lee AF, Nealon Seibert M, Bauer MS. Organizational Factors Influence on Mental Health Prescribing Behaviors at Community-Based Outpatient Clinics. Poster session presented at: AcademyHealth Annual Research Meeting; 2015 Jun 14; Minneapolis, MN. [view]
  4. Mohr DC, Simonetti T, Sylling PW, Nelson K, Joos S, Curtis I, Taylor L, Harvey HB, Schectman G, Fihn SD, Helfrich CD. Patient-Centered Medical Home Implementation and Burnout among VA Primary Care Employees. Poster session presented at: AcademyHealth Annual Research Meeting; 2015 Jun 15; Minneapolis, MN. [view]
  5. Bauer MS, Lee MF, Bajor L, Rasmusson A, Kazis LE. Spread of second generation antipsychotics for post-traumatic stress disorder. Poster session presented at: AcademyHealth Annual Research Meeting; 2013 Jun 25; Baltimore, MD. [view]
  6. Helfrich CD, Gale RC, Sylling PW, Mohr DC, Stockdale SE, Brown EJ, Asch SM, Nelson KM, Fihn SD, Meredith LS. Which facilitators and barriers have the strongest correlations with implementation of a patient-centered medical home in VA? Presented at: VA HSR&D / QUERI National Meeting; 2015 Jul 8; Philadelphia, PA. [view]

DRA: Mental, Cognitive and Behavioral Disorders
DRE: Treatment - Observational, Research Infrastructure
Keywords: none
MeSH Terms: none

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