title: Cost-effectiveness of active monitoring versus antidepressants for major depression in primary health care: a 12-month non-randomized controlled trial (INFAP study).
abstract: BACKGROUND
  Clinical practice guidelines for the treatment of major depressive disorder (MDD) recommend antidepressants for patients with moderate-severe depression and active monitoring for patients with mild-moderate symptoms. The feasibility and efficiency of active monitoring has not been proven conclusively. The aim of this study is to evaluate the cost-effectiveness of active monitoring in comparison to antidepressants for primary care patients with mild-moderate MDD.
  
  
  METHODS
  This is a 12-month follow-up multicenter observational prospective controlled trial. Patients are enrolled in 12 primary care centers in Barcelona (Spain). Eligible patients are adults (≥18 years-old) with a new episode of MDD that sign a written consent to participate. This is a naturalistic study in which general practitioners (GPs) use their professional judgment to allocate patients into active monitoring or antidepressants groups. GPs treat the patients following their clinical criteria. At baseline, GPs complete a questionnaire (sociodemographic/job characteristics, training, attitude towards depression, interest on mental health and participation in communication groups). Patients' measurements take place at baseline and after six and 12 months. Main outcome measures include severity of depression (PHQ-9), health-related quality of life (EuroQol-5D) and use of healthcare and social care services (Client Service Receipt Inventory). Secondary outcomes include diagnosis of MDD according to DSM-IV diagnostic criteria (SCID-I), disability (WHO-DAS), anxiety (BAI), comorbidities, medication side-effects and beliefs about medicines (BMQ). The analysis will be done according to the intention to treat analysis. Missing data will be imputed using multiple imputation by chained equations. To minimize the bias resulting from the lack of randomization, a propensity score will be used. Incremental effects and costs between groups will be modelled in each of the imputed databases using multivariate generalized linear models and then combined as per Rubin's rules. Propensity scores will be used to adjust the models. Incremental cost-effectiveness ratios will be calculated by dividing the difference in costs between groups by the difference in effects. To deal with the uncertainty, resampling techniques with bootstrapping will be used and cost-effectiveness planes and cost-effectiveness acceptability curves will be constructed. A series of sensitivity analyses will be performed.
  
  
  CONCLUSIONS
  Given the high burden and costs generated by depressive disorder, it is important that general practitioners treat major depression efficiently. Recent evidence has suggested that antidepressants have low benefits for patients with mild to moderate major depression. For such cases of depression, active monitoring exists as a treatment option, but it is not without difficulties for implementation and its effectiveness and efficiency have not been demonstrated conclusively. The results of the study will provide information on which is the most efficient approach to treat patients with mild to moderate major depression in primary care.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT02245373.
authors.affiliation: Fundació Sant Joan de Déu, Esplugues de Llobregat, Spain. mrubio@pssjd.org.|Primary Care Prevention and Health Promotion Research Network (RedIAPP), Barcelona, Spain. mrubio@pssjd.org.|School of Pharmacy, Universitat de Barcelona, Barcelona, Spain. mrubio@pssjd.org.
authors.forename: Maria
authors.initials: M
authors.lastname: Rubio-Valera
authors.affiliation: Fundació Sant Joan de Déu, Esplugues de Llobregat, Spain. ibeneitez@uoc.edu.|Open University of Catalonia (UOC), Barcelona, Spain. ibeneitez@uoc.edu.
authors.forename: Imma
authors.initials: I
authors.lastname: Beneitez
authors.affiliation: Primary Care Prevention and Health Promotion Research Network (RedIAPP), Barcelona, Spain. 32829mpm@comb.cat.|Primary Care Health Centre Bartomeu Fabrés Anglada, Servei d'Atenció Primària Delta Llobregat, Àmbit Costa de Ponent, Institut Català de la Salut, Gavà, Spain. 32829mpm@comb.cat.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Peñarrubia-María
authors.affiliation: Fundació Sant Joan de Déu, Esplugues de Llobregat, Spain. jvluciano@pssjd.org.|Primary Care Prevention and Health Promotion Research Network (RedIAPP), Barcelona, Spain. jvluciano@pssjd.org.|Open University of Catalonia (UOC), Barcelona, Spain. jvluciano@pssjd.org.
authors.forename: Juan V
authors.initials: JV
authors.lastname: Luciano
authors.affiliation: Primary Care Prevention and Health Promotion Research Network (RedIAPP), Barcelona, Spain. juanmmendive@gmail.com.|La Mina Primary Care Centre, Institut Català de la Salut, Sant Adrià de Besós, Barcelona, Spain. juanmmendive@gmail.com.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Mendive
authors.affiliation: Institute of Psychiatry, King's College London, De Crespigny Park, London, UK. paul.mccrone@kcl.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: McCrone
authors.affiliation: Personal Social Services Research Unit, London School of Economics and Political Science, Houghton Street, London, UK. m.knapp@lse.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Knapp
authors.affiliation: Institute for Prospective Technological Studies/Joint Research Centre, European Commission, Sevilla, Spain. ramon.sabes-figuera@ec.europa.eu.
authors.forename: Ramon
authors.initials: R
authors.lastname: Sabés-Figuera
authors.affiliation: Fundació Sant Joan de Déu, Esplugues de Llobregat, Spain. katie.kocyan@gmail.com.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kocyan
authors.affiliation: Miguel Servet Hospital, University of Zaragoza, Instituto Aragones de Ciencias de la Salud, Zaragoza, Spain. jgarcamp@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Campayo
authors.affiliation: Primary Care Prevention and Health Promotion Research Network (RedIAPP), Barcelona, Spain. aserrano@pssjd.org.|Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Spain. aserrano@pssjd.org.
authors.forename: Antoni
authors.initials: A
authors.lastname: Serrano-Blanco
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000191:economics* / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D003865:Major Depressive Disorder / Q000191:economics* / Q000628:therapy; D005260:Female; D058006:General Practice / Q000191:economics* / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000191:economics; D011446:Prospective Studies; D011788:Quality of Life; D013030:Spain; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D057832:Watchful Waiting / Q000191:economics*
chemical_list: D000928:Antidepressive Agents