Quality of guideline-concordant care and treatment for depression in the Veterans Health Administration and its impact on glycemic control

Transcription

1 University of Iowa Iowa Research Online Theses and Dissertations 2006 Quality of guideline-concordant care and treatment for depression in the Veterans Health Administration and its impact on glycemic control Laura Elizabeth Jones University of Iowa Copyright 2006 Laura Elizabeth Jones This dissertation is available at Iowa Research Online: Recommended Citation Jones, Laura Elizabeth. "Quality of guideline-concordant care and treatment for depression in the Veterans Health Administration and its impact on glycemic control." PhD (Doctor of Philosophy) thesis, University of Iowa, Follow this and additional works at: Part of the Epidemiology Commons

2 QUALITY OF GUIDELINE-CONCORDANT CARE AND TREATMENT FOR DEPRESSION IN THE VETERANS HEALTH ADMINISTRATION AND ITS IMPACT ON GLYCEMIC CONTROL by Laura Elizabeth Jones An Abstract Of a thesis submitted in partial fulfillment of the requirements for the Doctor of Philosophy degree in Epidemiology in the Graduate College of The University of Iowa May 2006 Thesis Supervisors: Adjunct Associate Professor Caroline Carney Doebbeling Professor James Torner

3 1 Depression is common and disproportionately affects those with chronic medical comorbidity, such as diabetes mellitus (DM). A limited amount of information is available concerning the quality of guideline-concordant treatment of depression and its influence on glycemic control among those with DM. This is the first study to address these issues in a veteran population with DM. This is a retrospective cohort study ( ) of veterans with and without DM from the Roudebush Veterans Affairs Medical Center in Indianapolis. Veterans with and without DM and a new episode of depression were identified. Administrative, clinical, and pharmacy data were linked to assess initiation of treatment, follow-up care, antidepressant dosage and duration, and change in antidepressant agent based on the Veterans Health Administration (VHA) clinical practice guidelines for depression. HbA1c levels were assessed at baseline and following initiation of antidepressant therapy. Depression treatment was not consistent with guideline recommendations. Only 60% of subjects received treatment within 30-days of the depression diagnosis. Veterans with DM were more likely to have received treatment within the first two weeks than veterans without DM. Few subjects received appropriate follow-up care for depression (<40%) or an adequate duration of antidepressant therapy (<9%). When treatment was provided, most subjects (88%) received a dosage consistent with guideline recommendations. The majority (>75%) were treated with a serotonigenic agent. Only 23% experienced a change in therapy during the treatment period, almost 84% of which received an adequate trial of therapy prior to change or augmentation of the agent. Presence of DM was associated with significantly increased odds for receipt of guideline-

4 2 concordant care for depression in most multivariate analyses. Receipt of guidelineconcordant care for depression was not a significant predictor of glycemic control but was associated with a clinically meaningful reduction (0.5%) in HbA1c levels. This research demonstrates that failure to adhere to depression treatment guidelines is common, but does not disproportionately affect those with DM. Guidelineconcordant treatment may positively influence glycemic control. Because the relationship between depression and DM is complex, further research is necessary to align current practice with evidence-based practices in the VHA. Abstract Approved: Thesis Supervisor Title and Department Date Thesis Supervisor Title and Department Date

5 QUALITY OF GUIDELINE-CONCORDANT CARE AND TREATMENT FOR DEPRESSION IN THE VETERANS HEALTH ADMINISTRATION AND ITS IMPACT ON GLYCEMIC CONTROL by Laura Elizabeth Jones A thesis submitted in partial fulfillment of the requirements for the Doctor of Philosophy degree in Epidemiology in the Graduate College of The University of Iowa May 2006 Thesis Supervisors: Adjunct Associate Professor Caroline Carney Doebbeling Professor James Torner

6 Copyright by LAURA ELIZABETH JONES 2006 All Rights Reserved

7 Graduate College The University of Iowa Iowa City, Iowa CERTIFICATE OF APPROVAL PH.D. THESIS This is to certify that the Ph.D. thesis of Laura Elizabeth Jones has been approved by the Examining Committee for the thesis requirement for the Doctor of Philosophy degree in Epidemiology at the May 2006 graduation. Thesis Committee: Caroline Carney Doebbeling, Thesis Supervisor James Torner, Thesis Supervisor Elizabeth Chrischilles William Clarke Carolyn Turvey

8 To my family for their support, endless encouragement, patience, and understanding; and especially to my parents for instilling in me the values of perseverance and hard work ii

9 ACKNOWLEDGMENTS I would like to acknowledge the inspirational instruction and guidance of many who have helped me realize and achieve my dreams. I am confident that those mentioned in these acknowledgements know just how remarkable their help has been but will also know just how heartfelt and genuine is my appreciation. A comprehensive acknowledgement would certainly require as many pages (if not more) than was necessary to finish this dissertation, but I would like to recognize just a few of the ways in which their expertise and guidance have been indispensable. I would like to thank the members of my dissertation committee (Drs. Carney Doebbeling, Torner, Chrischilles, Clarke, and Turvey) who have generously given their time, expertise, and wisdom over the past several years. I thank them for their contributions and support. Their collective insights and teachings have provided me with knowledge that will last a lifetime and which forms the foundation for my future work and academic pursuits. I am thankful to Dr. Clarke for his advice over the past five years. He always made biostatistics classes fun, the material easy to understand and conceptualize, all of which provide the underpinnings for the analytical portions of this project. I thank Dr. Turvey for the knowledge she shared in the psychiatric epidemiology class, from which the initial ideas for this project were derived. I especially appreciate her help and insight in the early phases as I was planning this project. Dr. Turvey s wisdom, encouragement, and feedback throughout all phases of the project were invaluable and greatly appreciated. I value the knowledge that Dr. Chrischilles shared with me in numerous epidemiology classes. She taught me to how to critically appraise the literature and how epidemiology fits in the wider context of scientific inquisition, which has iii

10 undoubtedly had lasting impact. I also thank my academic advisor for the last three years and co-chair of the thesis committee, Dr. Torner. His support, particularly in my last semester of academic coursework, is greatly appreciated. That support and encouragement kept me on track. And last, but certainly not least, I am greatly indebted to Dr. Carney Doebbeling who served as a co-chair of the dissertation committee and who has been my primary mentor for the last five years. Caroline, your insight, wisdom, patience, and guidance have and continue to enlighten me, inspire me, and are, and will always be, treasured. I am thankful to you for giving me the opportunity to work with you over the last five years, the practical experience that work has provided, and importantly, for sharing your passion for epidemiology and health services research with me. The ten million plus infideon number of ways you have supported me, helped me to achieve my goals, and realize success will never be forgotten. Not only did you teach me how to approach and conduct research, but you also taught me how to deal with reality. You helped motivate me to continue and to always strive for success even when things got tough. Your advice, ideas, feedback, support, encouragement, and friendship are valued. Although it took many years, I am thankful to you for inspiring me to believe that there are no such things as problems only temporary situations without a solution. I look forward to many more productive and successful years in the coming years. I would also like to thank Dr. Brad Doebbeling and Ada Yeung at the Roudebush VAMC in Indianapolis. Brad provided access to the data for this project, office space in which to conduct this work, insight and guidance, and contacts with other researchers who share similar interests. Brad, I am thankful for the many opportunities you have provided in the past year and the opportunities for future work. I also thank Ada for iv

11 sharing her knowledge, in-depth understanding of, and insight into the VHA databases and also for performing the initial data queries to obtain the data necessary for this project. Your knowledge and assistance cannot be overstated. I also sincerely appreciate you answering my many (and daily) questions on VHA data. I am also greatly appreciative of the Hardin Library and its extensive online collection of journal articles. Online (and off campus) access to the majority of articles cited in this dissertation greatly reduced the amount of time necessary to perform the background work of this dissertation and most importantly, allowed me to conduct such work late at night when I am most productive. Finally, I would like to thank my family for their support and for motivating me to never stop learning. To my mom and dad, thanks for providing the early foundation for me to succeed and for always believing in me. Always know that a part of my past and future triumphs is your victory as well. v

12 ABSTRACT Depression is common and disproportionately affects those with chronic medical comorbidity, such as diabetes mellitus (DM). Only a limited amount of information is available concerning the quality of guideline-concordant treatment of depression and its influence on glycemic control among those with DM. This is the first study to address these issues in a veteran population with DM. This is a retrospective cohort study ( ) of veterans with and without DM from the Roudebush Veterans Affairs Medical Center in Indianapolis. Veterans with and without DM and a new episode of depression were identified. Administrative, clinical, and pharmacy data were linked to assess initiation of treatment, follow-up care, antidepressant dosage and duration, and change in antidepressant agent based on the Veterans Health Administration (VHA) clinical practice guidelines for depression. HbA1c levels were assessed following initiation of antidepressant therapy. Treatment of depression was not consistent with guideline recommendations. Only 60% of subjects received treatment within 30-days of the depression diagnosis. Veterans with DM were more likely to have received treatment within the first two weeks than veterans without DM. Few subjects received appropriate follow-up care for depression (<40%) or an adequate duration of antidepressant therapy (<9%), although most (88%) received a dosage consistent with guideline recommendations when treatment was provided. Most subjects (>75%) were treated with a serotonigenic agent and only 23% experienced a change in therapy during the treatment period, almost 84% of which received an adequate trial of therapy prior to the change or augmentation in agent. Presence of DM was associated with significantly increased odds for receipt of vi

13 guideline-concordant care for depression in most multivariate analyses. Receipt of guideline-concordant care for depression was not a significant predictor of glycemic control but was associated with a clinically meaningful reduction of 0.5% in HbA1c levels. This research demonstrates that under-treatment of depression is common and may influence at least one medical outcome. Findings also support that the relationship between depression and DM is complex and that further research is necessary to help align current practice with evidence-based practices in the VHA. vii

14 TABLE OF CONTENTS LIST OF TABLES... xiii LIST OF FIGURES... xviii LIST OF ABBREVIATIONS...xix CHAPTER I INTRODUCTION...1 Overview...1 Significance of the Problem...3 Healthcare Costs...4 Healthcare Utilization...4 Morbidity and Mortality...8 Summary of Problems...10 Study Rationale...11 Study Overview...12 Specific Aims, Objectives, and Hypotheses...13 Significance of This Study...14 Summary...16 CHAPTER II REVIEW OF THE LITERATURE...17 Overview...17 Diabetes Mellitus...17 Clinical Definition...17 Overview and Epidemiology...17 Types of Diabetes Mellitus...19 Type Type Treatment of Diabetes Mellitus...23 Insulin...23 Oral Hypoglycemic Agents...24 Dietary Factors...25 Physical Activity...26 Monitoring of Glucose Levels...26 Summary of Treatment...30 Complications of Diabetes Mellitus...30 Macrovascular Disease...31 Microvascular Disease...32 Summary of Diabetes Mellitus Complications...35 Overall Summary of Diabetes Mellitus...36 Depression...36 Clinical Definition...36 Overview and Epidemiology...38 Prevalence...38 viii

15 Risk Factors...39 Problems Associated with Depression...39 Disability...40 Economic Burden...41 Psychiatric and Medical Comorbidity...41 Detection of Depression...43 Course and Treatment of Depression...44 Classes of Antidepressants...50 Serotonigenic Drugs...51 Heterocyclics...52 MAOIs...53 Dual-Acting Drugs...53 Other Agents...54 The Quality of Treatment for Depression...54 Guidelines for Measurement...54 Initiation of Antidepressant Therapy...56 Follow-up Care...58 Antidepressant Dosage...60 Antidepressant Duration...62 Predictive Factors...66 Summary of the Quality of Treatment of Depression...67 Overall Summary of Depression...68 Diabetes Mellitus and Depression...69 Overview and Epidemiology...69 Risk of Depression in the Diabetic Population...69 Prevalence of Depression in the Diabetic Population...69 Correlates of Depression in the Diabetic Population...72 Glycemic Control...73 Conceptual Framework...79 Healthcare System Factors...79 Predisposing Factors...80 Enabling Factors...80 Need...80 Health Behaviors...81 Outcomes...81 Description of Factors Related to Outcomes...81 Self-Care Behaviors...81 Treatment Factors...83 Psychosocial Factors...85 Physiologic Factors...87 Summary of Conceptual Framework...88 Treatment of Depression in Persons with Diabetes Mellitus...89 Overview...89 HbA1c Levels after Treatment of Depression...90 Depression Symptoms after Treatment of Depression...92 Limitations of Prior Depression Treatment Studies...94 ix

16 Summary...98 Quality of Antidepressant Therapy...99 Overall Summary of Diabetes Mellitus and Depression Gaps in Current Knowledge CHAPTER III METHODS Study Data Study Population Study Cohorts Study Inclusion Criteria Study Exclusion Criteria Identification of Diabetes Mellitus Identification of Depression Phases of Depression Treatment Pretreatment Period Acute Phase Continuation Phase Prescription Drugs Identification of Antidepressant Therapy Process Measures for VHA Guideline-Concordant Treatment of Depression Initiation of Depression Treatment Follow-up Visits Antidepressant Dosage Duration of Antidepressant Therapy Adequate Trial of Antidepressant Therapy Glycemic Control Potential Confounders Demographic Covariates Clinical Covariates Medical Comorbidity Psychiatric Comorbidity Prior Indication of Depression Type of Depression Body Mass Index Diabetes Mellitus Complications Diabetes Mellitus Treatment Modality and Medication Adherence Provider Type Healthcare Utilization Statistical Analysis Specific Aim 1 Analyses Description of the Cohort Univariate and Multivariate Modeling Procedures Objective 1.1: Initiation of Therapy Methods Objective 1.2: Follow-up Visits Methods x

17 Objective 1.3: Antidepressant Dosage Methods Objective 1.4: Duration of Antidepressant Therapy Methods Objective 1.5: Antidepressant Dosage and Duration Methods Objective 1.6: Adequate Trial of Antidepressant Therapy Methods Specific Aim 2 Analyses Description of the Cohort Methods CHAPTER IV RESULTS Description of the Study Cohorts Objective 1.1: Initiation of Depression Treatment Characteristics of Cohort 1 and Cohort Demographic Characteristics Clinical Characteristics Initiation of Depression Treatment Descriptive Results Univariate and Multivariate Analysis Characteristics of Cohort 3 and Cohort 4, Objectives Demographic Characteristics Clinical and Healthcare Utilization Characteristics Objective 1.2: Follow-up Visits Descriptive Results Univariate and Multivariate Analysis Objective 1.3: Antidepressant Dosage Descriptive Results Acute Phase: Univariate and Multivariate Results Continuation Phase: Univariate and Multivariate Results Treatment Phase: Univariate and Multivariate Results Objective 1.4: Duration of Antidepressant Therapy Descriptive Results Univariate and Multivariate Results Objective 1.5: Antidepressant Dosage and Duration Descriptive Results Univariate and Multivariate Results Objective 1.6: Adequate Trial of Antidepressant Therapy Descriptive Results Univariate and Multivariate Results Objective 2.1: Glycemic Control Characteristics of Cohort 5 and Cohort Demographic Characteristics Clinical Characteristics Healthcare Utilization Characteristics xi

18 Descriptive Results Univariate and Multivariate Results CHAPTER V DISCUSSION Initiation of Depression Treatment Summary Findings Discussion, Comparison, and Explanation of Findings Comparison of Study Findings Association between DM and Initiation of Therapy Barriers to and Outcomes of Treatment Correlates of Treatment for Depression Clinical Implications Follow-up Visits Summary Findings Discussion, Comparison, and Explanation of Findings Comparison of Study Findings Association between DM and Adequacy of Follow-up Barriers to and Outcomes of Adequate Follow-up Care Correlates of Adequate Follow-up for Depression Clinical Implications Antidepressant Dosage and Duration Summary Findings Discussion, Comparison, and Explanation of Findings Comparison and Explanation of Study Findings Association between DM and Treatment Adequacy Barriers to and Outcomes of Adequate Treatment Correlates of Adequate Treatment Clinical Implications Adequate Trial of Antidepressant Therapy Relationship between Quality of Depression Treatment and Glycemic Control Study Limitations Initiation of Treatment Follow-up Visits Antidepressant Dosage and Duration Change in Therapy Glycemic Control Study Strengths Conclusions APPENDIX A VETERANS HEALTH ADMINISTRATION INFORMATION APPENDIX B ICD-9 CODES FOR IDENTIFICATION OF COMORBIDITY APPENDIX C DESCRIPTION OF POTENTIAL CONFOUNDERS REFERENCES xii

19 LIST OF TABLES Table 1 Relationship between HbA1c Level and Plasma Glucose Levels Table 2 Unadjusted Prevalence Rates and Odds of Depression in Adults with Diabetes Mellitus in Controlled and Uncontrolled Studies by Type of Diabetes Mellitus, Gender, Setting, and Method of Depression Assessment Table 3 Demographic Characteristics for Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 4 Prevalence and Types of Chronic Medical Comorbidity among Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 5 Prevalence and Types of Psychiatric Comorbidity among Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 6 Clinical Characteristics of Depression for Veterans with and without Diabetes Mellitus (DM), Objective Table 7 Location of the Initial Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective Table 8 Initiation of Depression Treatment within 7-, 14-, 30-, and 60-Days of the Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective Table 9 Initial Type of Depression Therapy Provided and Number of Days until Receipt of First Treatment for Subjects (n=2,708) with and without Diabetes Mellitus (DM) who Received Treatment within 60-Days of the Depression Diagnosis, Objective Table 10 Types of Treatment for Depression Provided within 7-, 14-, 30-, and 60- Days of the Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective Table 11 Univariate and Multivariate Odds Ratios for Initiation of Treatment for Depression within 7-Days of the Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective Table 12 Univariate and Multivariate Odds Ratios for Initiation of Treatment for Depression within 14-Days of the Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective Table 13 Univariate and Multivariate Odds Ratios for Initiation of Treatment for Depression within 30-days of the Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective xiii

20 Table 14 Univariate and Multivariate Odds Ratios for Initiation of Treatment for Depression within 60-Days of the Depression Diagnosis for Veterans with and without Diabetes Mellitus (DM), Objective Table 15 Demographic Characteristics for Veterans with and without Diabetes Mellitus (DM) and Depression, Objectives Table 16 Prevalence and Types of Chronic Medical Comorbidity among Veterans with and without Diabetes Mellitus (DM) and Depression, Objectives Table 17 Prevalence and Types of Psychiatric Comorbidity among Veterans with and without Diabetes Mellitus (DM) and Depression, Objectives Table 18 Healthcare Utilization Characteristics for Veterans with and without Diabetes Mellitus (DM) and Depression during the 84-Day Acute Phase and the 180-Day Continuation Phase, Objectives Table 19 Clinical Characteristics of Depression for Veterans with and without Diabetes Mellitus (DM), Objectives Table 20 Follow-up Visits after Initiation of Antidepressant Therapy and Diagnosis of Depression for Veterans with and without Diabetes Mellitus (DM), Objective Table 21 Univariate and Multivariate Odds Ratios for Receipt of a Follow-up Visit within 7-Days of Antidepressant Initiation for Veterans with and without Diabetes Mellitus and Depression, Objective Table 22 Univariate and Multivariate Odds Ratios for Receipt of a Follow-up Visit within 14-Days of Antidepressant Initiation for Veterans with and without Diabetes Mellitus and Depression, Objective Table 23 Univariate and Multivariate Odds Ratios for Receipt of an Adequate Number of Follow-up Visits for Depression during the 84-Day Acute Phase of Depression Therapy, Objective Table 24 Receipt of a Minimum Therapeutic Antidepressant Dosage during the 84-Day Acute Phase, 180-Day Continuation Phase, and 264-Day Treatment Phase for Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 25 Univariate and Multivariate Odds Ratios for Receipt of a Minimum Therapeutic Antidepressant Dosage during the 84-Day Acute Phase of Therapy for Veterans with and without Diabetes Mellitus and Depression, Objective xiv

21 Table 26 Univariate and Multivariate Odds Ratios for Receipt of a Minimum Therapeutic Antidepressant Dosage during the 180-Day Continuation Phase of Therapy for Veterans with and without Diabetes Mellitus and Depression, Objective Table 27 Univariate and Multivariate Odds Ratios for Receipt of a Minimum Therapeutic Antidepressant Dosage during the 84-Day Acute and 264-Day Continuation Phase of Therapy for Veterans with and without Diabetes Mellitus and Depression, Objective Table 28 Medication Possession Ratios (MPR) during the 84-Day Acute Phase, 180-Day Continuation Phase, and 264-Day Treatment Phase of Depression for Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 29 Univariate and Multivariate Odds Ratios for Receipt of an Adequate Duration of Antidepressant Medication during the 84-Day Acute Phase of Therapy for Veterans with and without Diabetes Mellitus and Depression, Objective Table 30 Receipt of VHA Guideline Concordant Care for Depression for Veterans with and without Diabetes Mellitus (DM) during the 84-Day Acute Phase, 180- Day Continuation Phase, and 264-Day Treatment Phase, Objective Table 31 Univariate and Multivariate Odds Ratios for Receipt of VHA Guideline Concordant Care for Depression during the 84-Day Acute Phase of Therapy for Veterans with and without Diabetes Mellitus, Objective Table 32 Number and Types of Initial Antidepressant Agent(s) Filled by Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 33 Proportion of Subjects with and without Diabetes Mellitus (DM) that Experienced a Change in Antidepressant Therapy during the 264-Day Depression Treatment Period, Objective Table 34 Type of Change a in the Class of Antidepressant Medication for Veterans with and without Diabetes Mellitus (DM) and Depression, Objective Table 35 Receipt of an Adequate Trial of Antidepressant Therapy Prior to a Change in the Prescribed Antidepressant Agent, Objective Table 36 Univariate and Multivariate Odds Ratios for Receipt of an Adequate Trial of Antidepressant Therapy Prior to a Change in the Prescribed Antidepressant Agent, Objective xv

22 Table 37 Demographic Characteristics for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 38 Prevalence and Types of Chronic Medical Comorbidity for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 39 Prevalence and Types of Psychiatric Comorbidity for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 40 Prevalence and Types of Diabetic Complications for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 41 Clinical Characteristics for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 42 Outpatient Healthcare Utilization Received for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 43 Baseline and Follow-up Hemoglobin A1c (HbA1c) Levels for Veterans with Diabetes Mellitus (DM) who Received Adequate and Inadequate Depression Treatment, Objective Table 44 Baseline and Follow-up Hemoglobin A1c (HbA1c) Levels for Veterans with Diabetes Mellitus (DM) who Received Antidepressant Therapy in the 60- Day Period Prior to Receipt of Follow-up HbA1c Testing c, Objective Table 45 Univariate and Multivariate Relationship between Adequacy of Antidepressant Treatment and Glycemic Control among Veterans with Diabetes Mellitus, Objective Table A1 Veterans Health Administration Recommended Minimum Therapeutic Antidepressant Dosage According to Patient Age and Antidepressant Agent Table A2 VHA Clinic Stop Codes for Primary and Specialty Care Table B1 ICD-9 Codes for Identification of Medical Comorbidity Table B2 ICD-9 Codes for Identification of Psychiatric Comorbidity Table B3 ICD-9 Codes for Identification of Diabetic Complications Table C1 Variables Examined As Potential Confounders for Objective 1.1 and Objective xvi

23 Table C2 Variables Examined As Potential Confounders for Objectives Table C3 Variables Examined As Potential Confounders for Objective Table C4 Variables Examined As Potential Confounders for Objective xvii

24 LIST OF FIGURES Figure 1 Conceptual Model of Characteristics that Influence Treatment, Outcomes, and Determinants of Depression Quality Figure 2 Mean HbA1c Levels Before and After Randomization to Antidepressant Therapy or Placebo for Subjects with Diabetes Mellitus and Depression Figure 3 Mean Beck Depression Inventory (BDI) Scores Before and After Randomization to Antidepressant Therapy or Placebo for Subjects with Diabetes Mellitus and Depression Figure 4 Derivations of Study Cohorts Figure 5 Medication Possession Ratio (MPR) for Subjects with and without Diabetes Mellitus (DM) and Depression during the 84-Day Acute Phase of Depression Treatment Figure 6 Medication Possession Ratio (MPR) for Subjects with and without Diabetes Mellitus (DM) and Depression during the 180-Day Continuation Phase of Depression Treatment Figure 7 Medication Possession Ratio (MPR) for Subjects with and without Diabetes Mellitus (DM) and Depression during the 264-Day Treatment Phase of Depression Treatment xviii

25 LIST OF ABBREVIATIONS AACE ADA AHRQ ANCOVA AOR APA BDI BMI CI CPT DCCT DKA DM DSM-IV ECA ECT EMR ESRD GAF GTT HbA1c HEDIS HPA HSCL-90-R ICD-9 IFG IGT MAOI MPR NCS-R NOS OGTT OR PTSD SSRI UKPDS US VAMC VHA VISN VistA American Association of Clinical Endocrinology American Diabetes Association Agency for Healthcare Research and Quality Analysis of Covariance Adjusted Odds Ratio American Psychiatric Association Beck Depression Inventory Body Mass Index Confidence Interval Current Procedural Terminology Diabetes Control and Complications Trial Diabetic Ketoacidosis Diabetes Mellitus Diagnostic and Statistical Manual, Fourth Edition Epidemiologic Catchment Area Electroconvulsive Therapy Electronic Medical Record End-Stage Renal Disease Global Assessment of Functioning Glucose Tolerance Testing Hemoglobin A1c Health Plan Employer Data and Information Set Hypothalamic-Pituitary-Adrenal Hopkins Symptom Checklist-90, Revised International Classification of Diseases, Ninth Edition Impairment in Fasting Glucose Impairment in Glucose Tolerance Monoamine Oxidase Inhibitors Medication Possession Ratio National Comorbidity Survey Replication Not Otherwise Specified Oral Glucose Tolerance Test Odds Ratio Post-Traumatic Stress Disorder Selective-Serotonin Reuptake Inhibitors UK Prospective Diabetes Study United States Veterans Affairs Medical Center Veterans Health Administration Veterans Integrated Service Network Veterans Health Information Systems Technology Architecture xix

26 1 CHAPTER I INTRODUCTION Overview More than 20 million persons (7% of the population) in the United States (US) have diabetes mellitus (DM) and as many as 31% (>5.6 million persons) with DM have clinically significant depression. (1, 2) The medical and societal burden of DM and depression are significant public health problems due to increased healthcare costs, increased healthcare utilization, and the high rates of morbidity and mortality associated with these diseases. Much of the medical and societal burden of DM for persons with depression is due to poor glycemic control. Unsatisfactory glycemic control among persons with DM and depression may be the most important factor that leads to negative health sequelae, such as development and progression of DM complications. Retinopathy, nephropathy, and neuropathy are common concomitant and costly complications for persons with DM. Depression may further contribute to an increased risk of DM complications and economic burden due to poor lifestyle factors (e.g., physical inactivity) that contribute to inadequate glycemic control. More than 52% of diabetics with depression have hemoglobin A1c (HbA1c) levels 8%, higher than what the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) regard as optimal glycemic control. (3-6) Poorer glycemic control for depressed persons with DM may occur because <51% of patients are recognized as having depression and because <1/3 of patients with recognized depression receive adequate pharmacologic treatment for depression. (6-12) Inadequate treatment of depression may contribute to non-remission of depressive symptoms, reduced quality of life, increased incidence of other medical comorbidity (e.g., cardiovascular disease), increased healthcare utilization and costs, and suboptimal

27 2 glycemic control. In general, HbA1c levels may increase % due to depression. (13) Inadequate treatment of depression may not directly contribute to poor glycemic control, per se, but likely affects other lifestyle factors (e.g., physical activity, diet, glucose monitoring) that do contribute to poorer glycemic control. Research to date has not determined if depressed persons with DM receive adequate depression treatment during each phase of depression therapy. Results of a recent study suggested that glycemic control was not affected by the quality of antidepressant therapy, but the study methodology precludes our ability to make definitive conclusions regarding the association between quality of depression care and subsequent glycemic control. Depression treatment disparities among the medically ill are of significant concern, especially among diabetic patients who are burdened with a significant number of medical and psychiatric comorbidities and who have poor outcomes. Thus, research is needed to better understand the quality of depression care and associated outcomes in a medically ill population such that interventions can be developed to improve healthcare delivery and outcomes, if research shows that change is required. The May 2005 Veterans Health Administration (VHA) Mental Health Strategic Plan called for research to assess and remedy potential disparities in treatment and to assure that medical comorbidities are identified and addressed. Using DM as an example, this research study addresses the quality of depression treatment in a chronically ill veteran population at the Roudebush Veterans Affairs Medical Center (VAMC) in Indianapolis, Indiana to assess adherence to VHA depression clinical practice guidelines and whether guidelineconcordant care for depression influences glycemic control. The results of this study may

28 3 provide important information that may help to further improve the delivery of depression care in the VHA and other healthcare systems. Significance of the Problem DM and depression are significant public health problems. Estimates from a 2001 meta-analysis suggested that more than 11% of persons with DM in the general population met criteria for major depression but as many as 31% had elevated depressive symptoms. (2) Prevalence of depression in the DM population is likely even higher than is reported due to low recognition rates by patients and healthcare providers. Prevalence of DM and depression may be even more problematic in the VHA than in the general population due to sociodemographic correlates (e.g., low socioeconomic status), behavioral factors (e.g., smoking), and clinical characteristics (e.g., obesity, other medical and psychiatric comorbidity) that are common among VHA users. These factors are associated with DM, depression, quality of depression treatment, and poor glycemic control. (3, 14-27) It has been reported that as many as 20% of veterans who receive healthcare services from the VHA may have both DM and major depression, suggesting that an even higher percentage of veterans would have elevated depressive symptoms. (28) Depression in patients with DM is an important public health concern due to high healthcare costs, excess healthcare utilization, and high rates of morbidity and mortality. These problems may result if depressed persons with DM do not receive guidelineconcordant care for depression and if glycemic control is poorer for persons with depression. Each of these factors will be described in more detail to better illustrate the significance of the problem of DM and depression in the context as it relates to quality of treatment for depression and glycemic control, the foci of this research study.

29 4 Understanding the reasons why healthcare costs, healthcare utilization, morbidity, and mortality for persons with DM and depression are public health problems reinforce the necessity of further research and motivate the specific aims of this study. Healthcare Costs Direct healthcare costs are 2-5 times higher for persons with DM and depression as compared to costs incurred by persons with DM alone. (29-33) Direct healthcare costs exceed more than $190 billion per year and overall costs exceed $323 billion per year for persons with DM and depression, significantly higher than the estimated $132 billion in overall costs incurred by non-depressed persons with DM. (31) The direct healthcare costs incurred by persons with DM and depression account for >20% of the direct healthcare costs incurred by the entire US population. (31) In 1999, an individual with DM and depression incurred costs $10,358 greater than a non-depressed person with DM ($31,967 vs. $21,609). (33) Every 1% increase in HbA1c levels above 6% for patients with DM and depression increases healthcare expenditures by as much as $2,000. (33) This is significant given that many patients with DM and depression have HbA1c levels >8% and some have HbA1c levels >10%, which translates to an additional $8,000 in incurred costs. (3, 6, 34-36) Other independent factors that are significantly associated with increased healthcare costs for depressed persons with DM include race/ethnicity, age, and severity of the depression. (30-32) Therefore, it is reasonable to believe that provision of high quality depression treatment and adequate glycemic control would reduce healthcare expenditures. Healthcare Utilization Depressed persons with DM are frequent utilizers of inpatient and outpatient healthcare resources. (37, 38) Healthcare utilization by these persons is dependent on the

30 5 severity of the mental illness, age, gender, race/ethnicity, socioeconomic status, and burden of other medical and psychiatric comorbidity. (30) Excess healthcare usage may also be a function of the disease and due to the degree of other medical (e.g., cardiovascular disease) and psychiatric (e.g., anxiety disorder) comorbidity associated with both DM and depression. A study of Medicare beneficiaries reported that persons with DM and depression were 3.42 times more likely to have had an inpatient hospital admission, 2.30 times as likely to have been hospitalized for an ambulatory sensitive condition (i.e. conditions [e.g., foot ulcers, lower extremity amputations, metabolic decompensation] that could have been prevented had appropriate outpatient care been provided), and 2.83 times more likely to have received care in the emergency room as compared to non-depressed subjects with DM. (39) Another study reported that elderly patients with DM and depression experienced approximately fourteen additional nonmental healthcare visits in 1997 than did persons with DM who did not have depression. (30) Healthcare expenditures increased approximately 7% for this population and they had approximately 17% more days for which they were hospitalized for non-mental health reasons. (30) Increased healthcare utilization is not limited to only older adults with DM and depression. A study of younger adults also suggested that healthcare utilization was increased for persons with DM and depression as compared to the number of healthcare visits for non-depressed persons with DM (12 vs. 7 visits per year). (29) These results suggest that depression significantly influences healthcare utilization, but does not necessarily suggest that it is the depression, rather than the DM, that contributes to excess healthcare visits. Regardless, increased healthcare utilization correlates with

31 6 increased healthcare costs for the patient, the healthcare system, and for society that is responsible for providing healthcare services for the un- or under-insured. In recent years, the rate of inpatient care for veterans with DM has decreased while the rate of outpatient care increased 12.8% from 1997 to (40) The shift from inpatient care to outpatient care in the VHA occurred in the late 1990s due to a structural reorganization of the VHA healthcare system. (41) This structural reorganization reduced costs by 24% by providing healthcare services in the ambulatory care setting, which reduced the need for hospitalization. The VHA also focused on providing primary care to all eligible veterans in more than 1,300 access points, including hospitals and community clinics. The focus on primary care in the VHA translates into better access to healthcare services, prevention of disease, early detection of disease, and health promotion (e.g., smoking cessation counseling, weight loss). These factors are significant in the context of DM, depression, quality of care, and glycemic control because complications of DM may be prevented and healthcare costs and resource use, particularly inpatient hospitalizations, may be reduced if patients, physicians, and the healthcare system focus their efforts on provision of high quality care, achievement of optimal glycemic control, and elimination of unhealthy lifestyle habits. The transformation from inpatient care to outpatient care was also likely the result of the high quality of care provided to veterans on a consistent basis for treatment and prevention of DM, depression, and numerous other acute and chronic conditions. (42) Importantly, it may also be a reason why glycemic control has improved in the VHA in the last several years, but not in the general population. (43, 44) Although inpatient healthcare utilization has declined and outpatient utilization has increased in both the VHA and general population, healthcare utilization remains

32 7 elevated for persons with DM and depression as compared to persons with DM alone. (40) In general, increased healthcare utilization for persons with DM and depression may be the result of poorer glycemic control and/or inadequate treatment of depression. (3) Conversely, increased healthcare utilization may also correspond to better quality care for depression and better glycemic control due to more frequent contact with healthcare providers. For example, inadequate glycemic control, defined as HbA1c levels >7%, was 21% more likely in when utilization was rapidly increasing as compared to the rate of inadequate glycemic control in in the general population. Conversely, average HbA1c levels in the VHA fell from 8.4% in 1996 to 7.6% in 2000, just as the structural reorganization of the VHA was occurring. (43, 44) The effects of inadequate glycemic are profound. For example, patients with poor glycemic control (HbA1c level >10%) had more than double the number of inpatient admissions for acute DM complications than patients with good glycemic control (8.3 vs. 3.1), defined as HbA1c levels <8%. Those patients also had more than twice the number of hospitalizations (9.3 vs. 4.6) for acute DM complications. (45) Although it is unknown if the same relationship between glycemic control and healthcare utilization would be found for persons with DM and depression, it may be reasonable to assume that similar results would be observed based on evidence that suggests that HbA1c levels increase as the severity of the depression increases and because depressed persons with DM are frequent utilizers of healthcare services. Moreover, at least one study has reported that inadequate antidepressant therapy corresponds to at least a 1.2-fold greater risk of psychiatric hospitalization, but not overall hospitalization. (46) Too few studies have been conducted, and none that have specifically focused on persons with DM, to

33 8 determine how provision of adequate antidepressant therapy affects long-term healthcare utilization. Most studies have focused on utilization in the first year following therapy. Although some persons with depression may be likely to utilize healthcare services, significant barriers, such as obtaining and maintaining health insurance, healthcare costs, and lack of a consistent healthcare provider, impact the decision for other patients with depression in the general population to obtain medical care. (47, 48) A mental disorder may result in a 76% greater risk of delayed treatment seeking, solely due to healthcare costs. (47) A national survey found that persons with a probable depressive disorder were more than two times more likely to lose insurance benefits as compared to persons without a mental disorder (7.4% vs. 3.6%, respectively) and were significantly more likely to report that access to care was more difficult. (48) These are significant findings, especially for patients with DM, given the implications for poorer health outcomes and increased morbidity and mortality due to delayed treatment. However, the same barriers may not be problematic for persons who receive healthcare services from the VHA due to the organization of the VHA healthcare system, one advantage to addressing quality of healthcare and its impact on health outcomes in this population. Patients eligible for VHA care have, in general, access to the same services for free or drastically reduced costs, eliminating the financial barriers that plague access to care in the public sector. Morbidity and Mortality Third, DM and depression are significant public health problems because of increased morbidity and mortality. Factors that are associated with DM morbidity and mortality include age, gender, race/ethnicity, duration of DM, type of DM treatment, and depression. (49-51) Depressed persons with DM are at greater risk of developing

34 9 macrovascular complications (i.e. cardiovascular disease, stroke, and kidney disease) and DM microvascular complications (i.e. nephropathy, neuropathy, and retinopathy), which may help to explain why healthcare costs and utilization are significantly higher in this population. (22, 52) Among depressed persons with DM, 45% had multiple DM complications as compared to 35% of non-depressed persons with DM. (3) The percent of patients with at least one DM complication increases according to depression severity. For example, 37% of patients with a low depression severity were reported to have at least one DM complication as compared to 55% and 62% of patients with a medium and high depression severity, respectively. (32) This is significant because diabetics with higher levels of depression symptomatology are also less likely to partake in healthy lifestyle habits, which may further contribute to poorer glycemic control and the increased risk of the development of DM complications, possibly because these patients may be less likely to adhere to DM and depression medications. (36) It has been suggested that a high depression score was the single factor that most powerfully predicted hospitalization or death over a three-year period for older adults with DM in a prior study. (51) Depression may not only be associated with DM complications, but may also be related to the development and progression of these complications. It may be hypothesized that complications develop and progress more rapidly for patients with depression because of poor self-care behaviors, such as lack of adherence to DM and depression medications. (32) Or conversely, some pharmacologic treatments for depression may negatively affect insulin sensitivity due to associated side effects (e.g., weight gain), thereby contributing to poorer glycemic control.

35 10 Development and progression of DM complications may also be more problematic for persons with depression due to factors related to their care. Patients are responsible for 95% of their DM care, which means that patient noncompliance with prescribed medical and behavioral therapy (e.g., medication, diet, exercise, glucose monitoring) is an important factor that predicts unsatisfactory glycemic control. (32, 53-55) Adherence to prescribed medical and behavioral therapy are important not only for improved glycemic control, but because adherence to therapy is also associated with fewer healthcare visits and a reduction in healthcare costs as a result of depression improvement or remission and improved DM control. (56) In sum, adherence to therapy can help to prevent, or at least delay, the development or progression of DM complications for many patients. Although physicians are only responsible for 5% of a patient s DM control, healthcare provider noncompliance with recommended DM and depression clinical guidelines may also negatively influence depression outcomes and glycemic control. Provision of timely HbA1c testing and appropriate prescribing of pharmacologic treatment for DM and depression is the responsibility of healthcare providers for patients that present for medical care. Summary of Problems In summary, the medical and societal burden of DM and depression are significant public health problems for 31% of adults with DM, or >5.6 million persons in the US, and may be even more problematic in the VHA population. The effects of DM and depression are synergistic rather than additive. Depressed persons with DM may present an even greater challenge to the healthcare system. Poorer glycemic control generally requires increased healthcare utilization to treat the disease and its complications. This in turn corresponds to increased healthcare costs. These problems