Cochrane Library Cochrane Database of Systematic Reviews Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults (Protocol) Van Leeuwen E, van Driel ML, De Sutter AIM, Anderson K, Robertson L, Christiaens T Van Leeuwen E, van Driel ML, De Sutter AIM, Anderson K, Robertson L, Christiaens T. Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database of Systematic Reviews 2020, Issue 2. Art. No.: CD013495. DOI: 10.1002/14651858.CD013495. www.cochranelibrary.com Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults (Protocol) Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Cochrane Trusted evidence. Informed decisions. Library Better health. Cochrane Database of Systematic Reviews T A B L E O F C O N T E N T S HEADER......................................................................................................................................................................................................... 1 ABSTRACT..................................................................................................................................................................................................... 1 BACKGROUND.............................................................................................................................................................................................. 2 OBJECTIVES.................................................................................................................................................................................................. 5 METHODS..................................................................................................................................................................................................... 5 ACKNOWLEDGEMENTS................................................................................................................................................................................ 10 REFERENCES................................................................................................................................................................................................ 11 ADDITIONAL TABLES.................................................................................................................................................................................... 15 APPENDICES................................................................................................................................................................................................. 16 CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 19 DECLARATIONS OF INTEREST..................................................................................................................................................................... 19 SOURCES OF SUPPORT............................................................................................................................................................................... 19 Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults (Protocol) i Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Cochrane Trusted evidence. Informed decisions. Library Better health. Cochrane Database of Systematic Reviews [Intervention Protocol] Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults Ellen Van Leeuwen1,2, Mieke L van Driel3, An IM De Sutter2, Kristen Anderson4, Lindsay Robertson5, Thierry Christiaens1 1Clinical Pharmacology Unit of the Department of Pharmacology, Ghent University, Ghent, Belgium. 2Department of Family Medicine and Primary Health Care, Ghent University, Ghent, Belgium. 3Primary Care Clinical Unit, Faculty of Medicine, The University of Queensland, Brisbane, Australia. 4School of Pharmacy, The University of Queensland, Brisbane, Australia. 5Cochrane Common Mental Disorders, University of York, York, UK Contact address: Ellen Van Leeuwen, Clinical Pharmacology Unit of the Department of Pharmacology, Ghent University, Ghent, 9000, Belgium. [email protected]. Editorial group: Cochrane Common Mental Disorders Group Publication status and date: New, published in Issue 2, 2020. Citation: Van Leeuwen E, van Driel ML, De Sutter AIM, Anderson K, Robertson L, Christiaens T. Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database of Systematic Reviews 2020, Issue 2. Art. No.: CD013495. DOI: 10.1002/14651858.CD013495. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. A B S T R A C T This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the feasibility and safety of discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults aged over 18 years. Discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults (Protocol) 1 Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Cochrane Trusted evidence. Informed decisions. Library Better health. Cochrane Database of Systematic Reviews B A C K G R O U N D because of co-existing disease and drug-drug interactions related to other medications taken regularly (Kok 2017). Description of the condition Indications of antidepressants Antidepressant use Depressive disorders Antidepressants can be divided into various classes based on their slightly diFerent mechanisms of action (see Table 1). They The most prevalent condition that warrants the use of act, with a few exceptions, by enhancing the transmission of the antidepressants in the community and in nursing homes is chemical messengers dopamine, noradrenaline (norepinephrine), depression (Bourgeois 2012; Wong 2016). adrenaline (epinephrine) and serotonin, which are thought to be According to the Diagnostic and Statistical Manual of Mental involved in mood regulation in the brain. However, the exact Disorders 5th edition (DSM-V) classification, a major depressive mechanism of action of antidepressants is still not known (Harmer disorder is defined as a period of at least two weeks during 2017). which there is either depressed mood or the loss of interest or The consumption of antidepressants has increased significantly in pleasure in nearly all activities, and also at least four additional most countries since 2000 and continues to rise (OECD 2017). The symptoms from the following: changes in appetite, weight, sleep or highest use per population in the Convention on the Organisation psychomotor activity, decreased energy, feelings of worthlessness for Economic Co-operation and Development (OECD) Health or guilt, diFiculty concentrating or thinking or making decisions, Report is seen in Iceland, Australia, Portugal, UK, Sweden, Canada or recurrent thoughts of death or suicidal ideation or suicide plans and Belgium (OECD 2017). About 12.7% of Belgian adults take or attempts (APA 2013). The symptoms must persist for most of antidepressants daily (RIZIV 2014), with similar rates in the UK the day, nearly every day, for at least two consecutive weeks. The (16%; DHSC 2018), and many other European countries (Gusmão episode must be accompanied by clinically significant distress or 2013). In the USA the rate is about 12.7% (Pratt 2018), and in impairment in social, occupational or other important areas of Australia about 16.8% of adults take antidepressants daily (Brett functioning. A major depressive episode is a period of two weeks 2017). or more, characterised by the symptoms of a major depressive disorder (APA 2013). Severity of the major depressive disorder Like most prescribed medicines, antidepressants can have side- (mild, moderate, severe) must be based on the number of criterion eFects and adverse eFects. Very common (more than 10%) adverse symptoms, the severity of those symptoms and the extent to which events ('harms') for all antidepressants are sleep disturbance, usual social and working activity is limited and not rely simply on sexual dysfunction and gastro-intestinal problems. More serious counting the number of symptoms (APA 2013). rare adverse eFects (0.01% to 0.1%), are higher risk of agitation and suicide at the beginning of the treatment or when increasing Diagnosing depression can be diFicult due to these broad and dosage, gastro-intestinal bleeding, and in older people, low subjective diagnostic criteria and lack of a reliable and valid test for sodium in the blood with risk of agitation and confusion and an depression in primary care. increased risk of fracture (BCFI/CBIP 2018). Each antidepressant An untreated depressive episode typically lasts about four to is also associated with side eFects related to their mechanism six months on average (NICE 2016; Solomon 1997). Although of action. For example, very common side eFects (more than approximately half of the people who become depressed will 10%) of tricyclic agents (TCA) are blurred vision, constipation, and only have a single episode of depression in their lifetimes, dry mouth due to the anticholinergic properties of TCAs. Other approximately 50% will have multiple episodes or persistent common problematic anticholinergic eFects (1% to 10%), include