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Downloads/Solutio%20Comprehensive%20Formulary Nov06.Xls DEPRESSIVE DISORDERS AND CHRONIC COMORBID DISEASE STATES – A PHARMACOEPIDEMIOLOGICAL EVALUATION LIA KRITIOTIS DEPRESSIVE DISORDERS AND CHRONIC COMORBID DISEASE STATES – A PHARMACOEPIDEMIOLOGICAL EVALUATION LIA KRITIOTIS submitted in fulfilment of the requirements for the degree of MAGISTER SCIENTIAE in the FACULTY OF HEALTH SCIENCES at the NELSON MANDELA METROPOLITAN UNIVERSITY February 2007 Supervisor: Dr M Bellingan Co-supervisor: Prof I Truter I, Lia Kritiotis, hereby declare that the work on which this dissertation is based is original (except where acknowledgements indicate otherwise) and that neither the whole work nor any part of it has been, is being, or is to be submitted for another degree at this or any other university. ACKNOWLEDGEMENTS I am extremely grateful for having had the opportunity to conduct this study and would like to extend my sincere appreciation to the following people and institutions for making it possible for me to carry out this research: • Doctor Michelle Bellingan, my supervisor, for sharing her interest, advice and expertise regarding the field of Depressive Disorders, and for the guidance and encouragement shown throughout the study. On a more personal level, thank you for being a great teacher of the language of life. • Professor Ilse Truter, my co-supervisor, for her continuous support and motivation, and for her invaluable advice, which stems from a vast knowledge and experience in terms of drug utilisation reviews. In addition, thank you for being there when the language of life was difficult to interpret across the miles. • Mr Danie Venter for the time he dedicated towards broadening my statistical knowledge and for his assistance in this regard. • Pharmaceutical Benefit Management (Pty) Ltd. for the provision of data for this drug utilisation review. • The Nelson Mandela Metropolitan University for the financial assistance and the opportunity to further my academic career. • My family (in particular, my parents) for their patience, endless support, encouragement and understanding shown throughout the study. • My friends and colleagues for their patience and interest in the study. • My Saviour, for granting me the strength, determination and ability to fulfil my goal of completing this research undertaking. i DEPRESSIVE DISORDERS AND CHRONIC COMORBID DISEASE STATES – A PHARMACOEPIDEMIOLOGICAL EVALUATION CONTENTS Page LIST OF TABLES xi LIST OF FIGURES xvii SUMMARY xxiv KEY WORDS xxv CHAPTER 1 INTRODUCTION AND PROBLEM STATEMENT 1.1 INTRODUCTION 2 1.2 BACKGROUND TO THE STUDY 2 1.3 MOTIVATION FOR THE STUDY AND PROBLEM STATEMENT 8 1.4 PRIMARY AIM AND OBJECTIVES 9 1.5 CHAPTER LAYOUT 10 CHAPTER 2 DEPRESSIVE DISORDERS AND CHRONIC COMORBID DISEASE STATES 2.1 INTRODUCTION 13 2.2 DEFINITION OF MOOD DISORDERS 13 2.3 AETIOLOGY OF DEPRESSIVE DISORDERS 15 2.3.1 Environmental Factors 15 2.3.2 Genetic Factors 17 2.3.3 Iatrogenic Causes 18 2.3.4 Chronic Comorbid Disease States 19 2.3.5 Neurochemical Theories 21 2.3.5.1 The Monoamine Hypothesis 22 2.3.5.2 Dysregulation of Endocrine Systems 23 2.3.6 Other Hypotheses and Latest Developments 23 ii 2.4 DIAGNOSIS OF MOOD DISORDERS IN PATIENTS WITH CHRONIC DISEASE STATES 25 2.5 PREVALENCE OF DEPRESSIVE DISORDERS AND FACTORS AFFECTING PREVALENCE 29 2.5.1 Factors Affecting the Prevalence of Depressive Disorders 33 2.5.1.1 Age 34 2.5.1.2 Gender 36 2.6 DISEASES COMMONLY CO-EXISTING WITH DEPRESSIVE DISORDERS 38 2.6.1 Prevalence of Depressive Disorders with Chronic Comorbid Disease States 40 2.6.2 Proposed Explanations for the Link between Depressive Disorders and Chronic Comorbid Disease States 45 2.6.2.1 The Theory of Vascular Depression 46 2.6.2.2 Harmful Lifestyle Influences and Cardiac Risk Factors 47 2.6.2.3 Defining the Relationship Between Depressive Disorders and Cardiovascular Events 49 2.6.2.4 The Relationship between Hypertension and Depressive Disorders 52 2.6.2.5 The Relationship between Lipid Disorders and Depressive Disorders 53 2.6.2.6 The Relationship between Diabetes Mellitus and Depressive Disorders 54 2.6.2.7 The Relationship between Arthritis and Depressive Disorders 56 2.6.2.8 The Relationship between Menopause and Depressive Disorders 57 2.6.2.9 The Relationship between Hypothyroidism and Depressive Disorders 57 2.6.2.10 The Relationship between Asthma and Depressive Disorders 57 2.6.2.11 The Relationship between Neurological Disease States and Depressive Disorders 59 2.6.2.12 The Relationship between HIV-Disease and Depressive Disorders 61 2.7 THE IMPLICATIONS OF SUFFERING FROM A DEPRESSIVE DISORDER AND CHRONIC COMORBID DISEASE STATES 62 2.7.1 Non-compliance with Pharmacological and Non-pharmacological Therapies 63 2.7.2 The Detrimental Effects of Depressive Disorders and Chronic Comorbid Disease States on Outcomes 64 iii 2.7.3 The Financial and Occupational Implications of Being Diagnosed with a Depressive Disorder and One or More Chronic Comorbid Disease States 67 2.8 CONCLUSION 68 CHAPTER 3 TREATMENT OF DEPRESSIVE DISORDERS IN PATIENTS WITH PREVALENT CHRONIC COMORBID DISEASE STATES 3.1 INTRODUCTION 70 3.2 TREATMENT OF DEPRESSIVE DISORDERS 70 3.2.1 Treatment Phases for Depressive Disorders 70 3.2.2 Treatment Modalities for the Management of Depressive Disorders 72 3.2.2.1 Pharmacotherapy 74 3.2.2.2 Psychotherapy 74 3.2.2.3 Combination Therapy 75 3.2.3 Pharmacological Treatment of Depressive Disorders 75 3.2.3.1 Classification of Antidepressants 76 3.2.3.2 Non-selective Monoamine Re-uptake Inhibitors 78 3.2.3.3 Monoamine Oxidase Inhibitors 80 3.2.3.4 Selective Serotonin Re-uptake Inhibitors (SSRIs) 81 3.2.3.5 Other Antidepressants 85 3.3 Treatment Considerations in Special Populations 90 3.3.1 Treatment of Depressive Disorders in Children and Adolescents 90 3.3.2 Treatment of Depressive Disorders in the Elderly 92 3.4 Treatment of Depressive Disorders in the Presence of Commonly Occurring Comorbid Disease States 97 3.4.1 Treatment of Depressive Disorders and Comorbid Cardiovascular Disease States 97 3.4.1.1 TCAs: Implications for Cardiovascular Disease States 97 3.4.1.2 SSRIs: Implications for Cardiovascular Disease States 98 3.4.1.3 ‘Other Antidepressants’: Implications for Cardiovascular Disease States 100 3.4.1.4 Treatment of Depressive Disorders and Comorbid Diabetes Mellitus 104 iv 3.4.1.4.1 Cognitive Behavioural Therapy (CBT) 104 3.4.1.4.2 Antidepressant Treatment 104 3.4.1.4.3 Treatment of Diabetes Mellitus 107 3.4.2 Treatment of Depressive Disorders and Comorbid Arthritis 109 3.4.3 Treatment of Depressive Disorders in Menopausal Women 110 3.4.4 Treatment of Depressive Disorders and Comorbid Hypothyroidism 112 3.4.5 Treatment of Depressive Disorders and Comorbid Asthma 113 3.4.6 Treatment of Depressive Disorders and Comorbid Psychiatric and Neurological Disease States 114 3.4.6.1 Comorbid Psychiatric Disease States 114 3.4.6.2 Comorbid Neurological Disease States 117 3.4.6.2.1 Epilepsy 117 3.4.6.2.2 Alzheimer’s Disease 122 3.4.6.2.3 Parkinson’s Disease 122 3.4.6.2.4 Post-Stroke Depressive Disorders 124 3.4.7 Treatment of Depressive Disorders and Comorbid HIV-Disease 124 3.5 CONCLUSION 126 CHAPTER 4 METHODOLOGY 4.1 INTRODUCTION 128 4.2 LITERATURE REVIEW 128 4.3 DATA COLLECTION 129 4.3.1 Data Request 129 4.3.2 Data Format 129 4.4 DATA VERIFICATION 132 4.4.1 Diagnosis 132 4.4.1.1 Depressed Patients 132 4.4.1.2 Ambiguous Diagnoses 132 4.4.1.3 Age and Gender 133 4.5 DATA ANALYSES 133 4.5.1 Patient Demographics 134 4.5.2 Grouping of Diagnoses for Drug Utilisation Review 136 v 4.5.2.1 The ICD-10 Coding System 136 4.5.2.2 Diagnosis and ICD-10 Code Synchronisation 137 4.5.2.3 Grouping of Diagnoses for Drug Utilisation Review 137 4.5.3 Study Population Analyses: Entire Study Population 139 4.5.3.1 Characteristics of the Entire Study Population 139 4.5.3.2 Comorbidity Analysis 140 4.5.4 Study Population Analyses: Secondary Study Population 140 4.5.4.1 Characteristics of the Secondary Study Population 140 4.5.4.2 Analysis of Medications Prescribed for Depressive Disorders 142 4.5.5 Statistical Analyses and Methods Employed: Entire and Secondary Study Populations 143 4.5.5.1 Statistical Analyses 143 4.5.5.2 Methods Employed to Perform Analyses 145 4.6 CONFIDENTIALITY 145 4.7 LIMITATIONS OF THE STUDY 147 CHAPTER 5 RESULTS AND DISCUSSION: PREVALENCE OF DEPRESSIVE DISORDERS AND THE NATURE OF CHRONIC COMORBID DISEASE STATES IN DEPRESSED PATIENTS 5.1 CHARACTERISTICS OF THE STUDY POPULATION 149 5.1.1 Number of Patients 149 5.1.2 Age and Gender Distribution of the Study Population 149 5.1.3 Diagnostic Classification and Prevalence of Depressive Disorders Relative to Age and Gender 153 5.2 EPIDEMIOLOGICAL ANALYSIS OF COMORBID DISEASE STATES IN DEPRESSED PATIENTS 158 5.2.1 Number of Chronic Comorbid Disease States per Depressed Patient 158 5.2.2 Overview of the Most Prevalent Chronic Comorbid Disease States in the Study Population 162 5.3 Age Group Analysis: 0 to 17 Years 168 5.3.1 Age and Gender Distribution of Depressed Patients 168 5.3.2 Comorbidity Analysis 170 vi 5.3.2.1 Number of Chronic Comorbid Disease States per Depressed Patient 170 5.3.2.2 Most Prevalent Chronic Comorbid Disease States 171 5.4 Age Group Analysis: 18 to 34 Years 177 5.4.1 Age and Gender Distribution of Depressed Patients 177 5.4.2 Comorbidity Analysis 178 5.4.2.1 Number of Chronic Comorbid Disease States per Depressed Patient 178 5.4.2.2 Most Prevalent Chronic Comorbid Disease States 180 5.5 Age Group Analysis: 35 to 54 Years 188 5.5.1 Age and Gender Distribution of Depressed Patients 188 5.5.2 Comorbidity Analysis 189 5.5.2.1 Number of Chronic Comorbid Disease States per
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