Evidence based Psychiatric Care Journal of the Italian Society of Psychiatry Updates in treating major depressive Società Italiana di Psichiatria disorder in the elderly: a systematic review Mario Amore1,2, Andrea Aguglia1,2, Gianluca Serafini1,2, Andrea Amerio1,2,3 1 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy; 2 IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 3 Department of Psychiatry, Tufts University, Boston, USA Summary Among mental disorders, late life depression occurs in 7% of the general older population. Mario Amore An updated systematic review of randomized controlled trials (RCTs) on phar- macological and non-pharmacological treatment of major depressive disorder (MDD) in the elderly was conducted. Eight RCTs were carried out on 663 patients (mean age 70.99, SD 6.73). Vor- How to cite this article: Amore M, tioxetine (p = 0.897), saffron (η2 = 0.008) and tianeptine (p = 0.32) reduced Aguglia A, Serafini G, et al. Updates in depressive symptoms in MDD older adults, although no significant differences treating major depressive disorder in the in their efficacy were found when compared to sertraline and escitalopram, re- elderly: a systematic review. Evidence- spectively. Focusing on adverse events, in comparison with sertraline, vortiox- based Psychiatric Care 2021;7:23-31. https://doi.org/10.36180/2421-4469- etine did not show any significantly difference, while saffron was associated to 2021-5 less neurological disorders (RR 0.13, 95% CI 0.17-0.93, p = 0.02). Neurological (RR 0.46, 95% CI 0.3-0.71, p = 0.000) and gastrointestinal (RR 0.54, 95% CI Correspondence: 0.31-0.96, p = 0.04) disorders were also less common in patients under tianep- Mario Amore tine compared to escitalopram. [email protected] Although significant effects for some pharmacological and non-pharmacolog- ical interventions in older patients, the overall MDD evidence is still scant and Conflict of interest more studies are needed in this vulnerable segment of population. The Authors declare no conflict of interest. Fundings Key words: elderly, major depressive disorder, treatment This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Author contributions Introduction The manuscript has been approved by The world’s population is ageing rapidly. As reported by the World Health Or- all authors. Studies were identified and ganization (WHO), between 2015 and 2050, the proportion of the world’s older independently reviewed for eligibility by adults is estimated to almost double from about 12% to 22% 1. Older adults the two authors (Amerio, Aguglia) in a two- make important contributions to society as family members, volunteers and as step based process. Data were extracted active participants in the workforce. The protection of the physical and mental by one author (Amerio) and supervised by a second author (Serafini) using an ad-hoc health status of this vulnerable segment of population needs to be recognized developed data extraction spreadsheet. 2 as a real public health priority . Our manuscript has been approved by all Among mental disorders, late life depression occurs in 7% of the general older authors. population and accounts for 5.7% of Years Lived with Disability (YLDs) among those over 60 years old 1. Diagnosing depression in older adults can be more This is an open access article distributed in accordance with the CC-BY-NC-ND (Creative difficult than in young people because of physical comorbidities and cognitive Commons Attribution-NonCommercial-NoDerivatives dysfunction 3,4. Depressive symptoms are often overlooked and untreated and 4.0 International) license. The article can be used by they are accompanied by poorer functioning compared to chronic medical con- giving appropriate credit and mentioning the license, but only for non-commercial purposes and only in 5,6 ditions . Moreover, depression can increase the perception of poor health, the original version. For further information: https:// the utilization of health care services and costs, as well as the burden on their creativecommons.org/licenses/by-nc-nd/4.0/deed.en families and caregivers 7. There is no single preferred intervention for depression in older adults, and Open Access a wide variety of treatments can be used 8. Findings from a systematic re- © Copyright by Pacini Editore Srl Evidence-based Psychiatric Care 2021;7:23-31; doi: 10.36180/2421-4469-2021-5 23 M. Amore et al. view conducted in 2017 by Krause and colleagues on Outcomes randomized controlled trials (RCTs) revealed several an- tidepressants and quetiapine to be efficacious in elderly The number of patients responding to treatment was the patients with major depressive disorder (MDD), but due main outcome, defined as a score reduction of at least to the comparably few available data, results were not ro- 50% from baseline to endpoint or follow-up on a validated bust 9. Moreover, although significant effects were found scale. In addition, remission of symptoms was defined as: for some non-pharmacological treatments, the overall evi- 7 or less on the 17-item Hamilton Depression Rating Scale dence was insufficient, because of based on a few trials (HDRS); 8 or less for longer versions of HDRS; 6 or less on with small sample sizes 10. the Montgomery-Asberg-Depression Scale (MADRS); 10 or less on the Beck Depression Inventory (BDI); 5 or less Aim of the study on the Geriatric Depression scale (GDS). The mean reduc- tion of depressive symptoms from baseline to the endpoint We updated Krause and colleagues’ systematic review of was also investigated. Moreover, the incidence and main all RCTs on pharmacological and non-pharmacological causes of adverse events were included as outcomes of treatment of MDD in the elderly to provide recommenda- primary interest, as well as dropouts, deaths, and suicides. tions for clinical management and future research. Study selection and data extraction Methods Identified studies were independently reviewed for eligi- bility by the two authors (MA, AA) in a two-step process: Information sources and search strategy a first screening was performed based on titles and ab- stracts, then full texts were retrieved for a second screen- This systematic review was conducted according to meth- ing. Disagreement was resolved by consensus. Data were ods recommended by the Cochrane Collaboration and the extracted using an ad-hoc developed data extraction Preferred Reporting Items for Systematic Reviews and spreadsheet. Meta-Analyses (PRISMA) guidelines 11,12. Studies were identified searching the electronic databases MEDLINE, Data items Embase, PyscInfo, CINAHL, ClinicalTrials.gov, Web of Science, and the Cochrane Library. We combined free text Information was extracted from each included study on: terms and MeSH heading as described in Appendix 1. As 1) study design, time and country of intervention, sample done before 13,14, the strategy was first developed in MED- size, study arms; 2) age, sex and comorbidities of par- LINE and then adapted for use in the other databases. ticipants; 3) type, name, dose and duration of interven- Studies in English published from December 12th, 2017 tions and controls; 4) name of rating scales, baseline and to January 1st, 2021 were included. In addition, further completion mean rating scores in study groups, Relative studies were retrieved from reference listing of relevant Risks (RRs) of response to treatment and symptom remis- articles and consultation with experts in the field. sion; 5) frequencies and descriptions of adverse events and dropouts. Study population and study designs Quality assessment We searched for RCTs carried out in elderly patients with a primary diagnosis of major depressive disorder. The di- The revised Cochrane risk of bias tool for randomized tri- agnosis was made according to the Diagnostic and Statis- als (RoB 2) was used to assess the risk of bias in indi- 15 tical Manual (DSM) criteria for major depressive disorder, vidual studies . or the International Statistical Classification of Diseases (ICD-10) criteria for recurrent depressive disorder. Studies Results using other diagnostic criteria were excluded. However, as 9 done previously , given the variety of depressive forms, Study selection studies were accepted if less than 20% of population had another form of depression. Studies of relapse prevention Six hundred eighty potential studies were identified from carried out in non-acute patients were excluded. the selected databases and after cross-checking refer- ences of relevant articles. Five hundred ninety-five stud- Interventions ies were retrieved after duplicate removal. Studies were Pharmacological and non-pharmacological interventions, screened and selected as described in Figure 1. Eight such as psychotherapy and physical activity, were includ- RCTs were included in the systematic review. ed. Active controls were allowed as well as placebo. Due Study characteristics and populations to either scarce clinical relevance for the elderly and the risk of confounding factors, we excluded studies of com- Characteristics of included studies are reported in Table I. bination therapy. All the studies were RCTs and half were double-blind- 24 Updates in treating MDD in the elderl Records Records Records Records Records Records identified identified identified identified identified identified through THE through through through through through