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Background Paper 6.15 Depression Priority Medicines for Europe and the World "A Public Health Approach to Innovation" Update on 2004 Background Paper Written by Eduardo Sabaté Background Paper 6.15 Depression By Julisca Cesar & Fáraz Chavoushi April 2013 Update on 2004 Background Paper, BP 6.15 Depression Table of Contents Acknowledgements ............................................................................................................................................ 3 Abbreviations used in this report .................................................................................................................... 4 1. Introduction ................................................................................................................................................. 5 1.1 Definition and classifications ............................................................................................................ 5 1.2 Natural history .................................................................................................................................... 7 1.3 Comorbidities and risk factors .......................................................................................................... 8 1.4 Depression in young people ........................................................................................................... 11 1.5 Depression in the elderly ................................................................................................................. 12 2. Epidemiology and burden of depression............................................................................................. 12 3. Economic aspects of depression ............................................................................................................ 16 4. Control strategy ........................................................................................................................................ 18 4.1 Diagnosis ........................................................................................................................................... 19 4.2 Treatment ........................................................................................................................................... 21 4.2.1 Antidepressant medicines ........................................................................................................... 22 4.2.2 Psychotherapy .............................................................................................................................. 34 4.2.3 Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) ................ 35 4.3 Prevention .......................................................................................................................................... 37 5. Persistence of the disease ........................................................................................................................ 37 6. Past and current research on depression .............................................................................................. 39 6.1 EC Funded research on depression ................................................................................................ 39 6.2 Past and current trials ...................................................................................................................... 40 6.3 Pharmaceutical pipeline .................................................................................................................. 42 7. Research gaps ............................................................................................................................................ 43 8. Conclusions ............................................................................................................................................... 45 References ........................................................................................................................................................... 47 Annexes ............................................................................................................................................................... 61 Annex 6.15.1: Overview of ICD-10 and DSM-IV classifications of mood disorders 8,9 ........................ 61 Annex 6.15.2: EC Sixth and Seventh Framework Projects focusing on depression .............................. 62 Annex 6.15.3: Search strategy for data on past and current research related to MDD ........................ 66 Annex 6.15.4: NICE 2009 depression guidelines: Recommendations for research gaps ...................... 67 Appendices ......................................................................................................................................................... 69 Appendix 6.15.1: Active compounds in the pharmaceutical pipeline since 2009. ................................ 69 6.15-2 Update on 2004 Background Paper, BP 6.15 Depression Appendix 6.15.2: Common antidepressive agents, their trade name, drug class and mechanism of action. .............................................................................................................................................................. 74 Appendix 6.15.3: Common antidepressive agents and associated side effects. .................................... 75 Acknowledgements We would like to thank all reviewers who have contributed to the writing of this background paper. Specifically, we would like to thank Dr. M. Taghi Yasamy, of the Mental Health Department of the World Health Organization and S. Hove Marsling from H. Lundbeck A/S for their valuable contributions. 6.15-3 Update on 2004 Background Paper, BP 6.15 Depression Abbreviations used in this report CBT Cognitive behavioral therapy DALY Disability-adjusted life year EC European commission ECT Electroconvulsive therapy FP6 Sixth EC Framework Programme FP7 Seventh EC Framework Programme GBD Global burden of disease GDP Gross domestic product HRSD Hamilton rating scale for depression IAPT Improving access to psychological therapies programme IPT Interpersonal therapy LMIC Low and/or Middle Income Countries LPT Lost productive time MAOI Monoamine oxidase inhibitors MDD Major depressive disorder mhGAP IG Mental health GAP intervention guide NARI Noradrenaline reuptake inhibitors NASSA Noradrenaline and specific serotoninergic antidepressants PP Phenylpiperazine QALY Quality-adjusted life year R &D Research and development SNRI Serotonin and noradrenaline reuptake Inhibitors SSRI Selective serotonin reuptake inhibitors TMS Transcranial magnetic stimulation TRD Treatment resistant depression TRI Triple reuptake inhibitors YLD Year lived with disability WFMH World Federation of Mental Health 6.15-4 Update on 2004 Background Paper, BP 6.15 Depression 1. Introduction This paper is an update of the background paper for Chapter 6.15 of the 2004 Priority Medicines for Europe and the World.1 (Published at: http://archives.who.int/prioritymeds/report/background/depression.doc.) This background paper describes demographic trends and the burden of disease of major depression disorder (MDD) for the European Union Member States and the world as a whole, assesses the current treatment options available for MDD as well as the treatments under development and makes recommendations on future research priorities. The paper demonstrates data and trends derived (mainly) from the recently published 2010 Global Burden of Disease study.2,3 It particularly addresses the epidemiology, the burden of disease, treatment options, and the economic impact of MDD. Furthermore, this background paper describes specific groups within the society that are often misdiagnosed and/or undertreated, or not diagnosed and treated at all. Depression is a common mental disorder that presents with depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, and poor concentration.4,5 It usually occurs as a result of adverse life events, such as: losses of a significant person, object, relationship or health, but it can also occur due to no apparent cause.4 These problems can become chronic or recurrent and lead to substantial impairments in an individual's ability to take care of his or her every day responsibilities.6 Mood disorders are treatable conditions, with each type requiring different treatment approaches and modalities. Antidepressant medications and psychotherapies offer useful treatment approaches and are commonly employed in treating the debilitating effects of depression. If mood disorders like depression are left untreated for long periods of time, the debilitating effects of depression cause unnecessary suffering that intervenes with people’s daily-life activities.7 1.1 Definition and classifications The Oxford English Dictionary defines depression as “a mental condition characterized by severe feelings of hopelessness and inadequacy, typically accompanied by a lack of energy and interest in life.”8 In the medical and social sciences depression is defined in several different ways that will be discussed in this section. Two frequently used classification systems are the ICD-10 (International Classification of diseases, 10th edition) and the DSM-IV (Diagnostic and statistical manual of mental disorders, fourth edition)9,10 Annex 6.15.1 provides an overview of the classifications used by these two systems. The ICD has been endorsed by the World Health Organization as a standard diagnostic tool for epidemiology, health management and
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