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Supplementary dataTable S SEQ Table_A \* ARABIC 1: Search strategy for economic burden of treatment resistant depression in major depressive disorder#SearchesResults1cohort studies.mp. or Cohort Studies/2291542epidemiologic methods.mp. or Epidemiologic Methods/321263epidemiologic studies.mp. or Epidemiologic Studies/252854epidemiology.mp. or Epidemiology/1945415cohort analysis.mp. or Cohort Studies/2188526Longitudinal Studies/ or longitudinal stud*.mp.1396857Prospective Studies/ or prospective stud*.mp.5219698Follow-Up Studies/ or follow-up stud*.mp.6097419Retrospective Studies/ or retrospective stud*.mp.69116810observational stud*.mp.9957911(observational adj3 (study or studies or design or analysis or analyses)).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]120163121 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11208539513Insurance, Disability/ or disability.mp.19144214disable*.mp.7395615lost work time.mp.20516absenteeism.mp. or Absenteeism/1087317sick leave.mp. or Sick Leave/729918presenteeism.mp. or Work/ or Workplace/3797219(cost adj indirect).mp.2120productivity.mp.4390421indirect resource u*.mp.92213 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 2132810323costs.mp. or "Costs and Cost Analysis"/23010824Economics, Hospital/ or Economics, Pharmaceutical/ or Economics/ or Economics, Nursing/ or economic$.mp. or Economics, Medical/ or Economics, Behavioral/27141225"Cost of Illness"/ or Health Care Costs/ or indirect costs.mp.5607026Cost allocation/202327Health care costs/3409228Direct service costs/114429exp economics, medical/1420130(health?care adj cost$).mp.753631(cost adj estimate$).mp.185832(cost adj variable).mp.3933(unit adj cost$).mp.204534(cost* or economic*).mp.76741235(health$care adj resource).mp.134636resource u*.mp.1432237Caregiver/ or caregiver.mp.394733823 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 378101443922 or 38110200940Depressive Disorder, Major/ or MDD.mp.2892441treatment-resistant depression.mp. or Depressive Disorder, Treatment-Resistant/20434240 or 41302284312 and 39 and 4256744limit 43 to animals14543 not 4456646remove duplicates from 4552647limit 46 to ed=19000101-20170427511Table S SEQ Table_A \* ARABIC 2: Search strategy for patient HRQoL burden in treatment resistant depression in major depressive disorder#SearchesResults1Depressive Disorder, Major/ or MDD.mp.289242treatment-resistant depression.mp. or Depressive Disorder, Treatment-Resistant/204331 or 2302284(utility value or utilit*).mp.1643915Patient Preference/ or preference*.mp.1338896(standard gamble or SG).mp.83377(time trade-off or TTO).mp.14218EQ-5D.mp.52849EuroQoL-5D.mp.94610(SF-36 or SF-6D or SF-12).mp.2082511(HUI or Health utilities index).mp.136612(QALY or quality-adjusted life year).mp.801213Quality-Adjusted Life Years/9679144 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13334904153 and 1499016remove duplicates from 1592117limit 16 to ed=19000101-20170427864Table S3: Population, Interventions, Comparators, Outcomes, Study design criteria for study inclusion and exclusionInclusionExclusionPopulation?Individuals with MDD and non-response to drug treatment step 1 were eligible for inclusion in the review.?Mixed study populations (e.g., combined unipolar and bipolar depression where distinction is not provided)?Study populations for which treatment resistance could not be reasonably inferred (e.g., received ECT treatment vs. non-ECT) ?Animal studiesInterventions?No restriction?Not ApplicableComparators?Studies comparing patients with TRD to non-responders to treatment step 1 (i.e., first-line pharmacotherapy) are of primary interest, however, other comparators as defined by study-level authors that served as proxies for TRD and/or non-response were also included ?Not ApplicableOutcomes?HRQoLa from the patient perspective?Work-related outcomes including functional outcomes (e.g., disability; inability to work)?Healthcare resource utilization?Costs?Caregiver burden outcomes?Outcomes that do not characterize patient, societal, or economic impacts Study Design?Prospective/retrospective cohort studies?Economic modeling studies?Published abstracts for which full-text peer-reviewed publications were not available?Burden measured in the context of a randomized clinical trial?Grey literaturea HRQoL includes both indirectly- and directly-elicited utilities; HRQoL = Health-related quality of life; MDD = Major Depressive Disorder; MDE=Major Depressive Episode; PICOS = patients, intervention, comparator, outcomes, study design; TRD = Treatment-resistant depressionTable S4: Total direct and indirect costs (inflated to 2017 USD) in studies included in the economics systematic review of treatment resistant depression (N = 10)Publication / CountryPopulationTRD ranking* N Direct medical costsIndirect medical costsIncreasing costs with increasing treatment resistance?Feldman et al., 2013/USAManaged depressed sample**16,00511,044Not reportedYesTRD sample**23,79716,786Gibson et al., 2010/USAMGH-AD <3.5 (no augmentation)110,235 Not reportedYesMGH-AD 3.5-4 (no augmentation)212,425 MGH-AD 4.5-5 (no augmentation)313,261 MGH-AD 5.5-6 (no augmentation)414,792 MGH-AD >=6.5516,570 Incremental cost: Augmentation with atypical antipsychotic+1,661 Incremental cost: Augmentation with stimulants+3,347 Incremental cost: Adjunctive therapy with mood stabilizer+7,723 Greenberg et al., 2004/USANon-depressed sample of employees1Not reported4,673 3,336YesManaged depressed employees21,5127,0756,129TRD employees318016,57813,119Ivanova et al., 2010/USAManaged depressed employees12,3128,0564,727YesTRD employees22,31215,6438,764Khandker et al.,2008/USANon-switchers***146,5728,536Not reportedYesSwitchers***22,37811,935Lepine et al., 2012/BrazilManaged depression11222,089Not reportedYesTRD 2903,791Olchanski et al., 2013/USAManaged depression158,69711,141Not reportedYesTRD 224,41519,382Schultz and Joish, 2009/USAMaintainers14,2339,5962,039YesSwitchers22,93114,3832,979Augmenters310914,4202,877Sicras-Mainar et al., 2014/SpainRemission****16421,824730Non-remission****25132,6791,145von Knorring et al., 2006/SwedenResponders168729,71125,290YesNon-responders234448,88843,511*TRD ranking defined as 1=least resistant category and increases with increasing resistance. **TRD and managed depressed sample outcomes calculated by taking a weighted average based on presence of negative events. *** Weighted average taken of SSRI and SNRI groups ****Weighted average taken of treatment groupsMDD = Major Depressive Disorder; SNRI = Serotonin-norepinephrine reuptake inhibitor ; SSRI = Selective serotonin reuptake inhibitor TRD = Treatment-resistant depression; USA=United States of America ................
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