Cost-effectiveness of antidepressants versus active monitoring for mild-to-moderate major depressive disorder: a multisite non-randomized-controlled trial in primary care (INFAP study)

  • Maria Rubio-ValeraEmail author
  • María Teresa Peñarrubia-María
  • Maria Iglesias-González
  • Martin Knapp
  • Paul McCrone
  • Marta Roig
  • Ramón Sabes-Figuera
  • Juan V. Luciano
  • Juan M. Mendive
  • Ana Gabriela Murrugara-Centurión
  • Jordi Alonso
  • Antoni Serrano-Blanco
Original Paper



The purpose of this study was to evaluate the cost-effectiveness of antidepressants vs active monitoring (AM) for patients with mild–moderate major depressive disorder.


This was a 12-month observational prospective controlled trial. Adult patients with a new episode of major depression were invited to participate and assigned to AM or antidepressants according to General Practitioners’ clinical judgment and experience. Patients were evaluated at baseline, and 6 and 12-month follow-up. Quality-adjusted life years (QALYs) gained were estimated and used to calculate incremental cost–utility ratios (ICUR) from the healthcare and government perspective. To minimize the bias resulting from non-randomization, a propensity score-based method was used.


At 6 and 12-month follow-up, ICUR was 2549 €/QALY and 6,142 €/QALY, respectively, in favor of antidepressants. At 6 months, for a willingness to pay (WTP) of 25,000 €/QALY, antidepressants had a probability of 0.89 (healthcare perspective) and 0.81 (government perspective) of being more cost-effective than AM. At 12 months, this probability was 0.86 (healthcare perspective) and 0.73 (government perspective).


Incremental cost–utility ratios favor pharmacological treatment as a first-line approach for patients with mild–moderate major depressive disorder. While our results should be interpreted with caution and further real world research is needed, clinical practice guidelines should consider antidepressant therapy for mild–moderate major depressive patients as an alternative to active monitoring in PC.


Depression/mood disorder Antidepressant medication Primary care Health economics 



The study was approved by the Clinical Research Ethics Committee at the Sant Joan de Déu Foundation (EPA-24-12) and the Clinical Research Ethics Committee at The Jordi Gol i Gurina Foundation (5013-002). All the participants signed an informed consent form. This study was supported by a grant from the “Instituto de Salud Carlos III, Ministerio de Economía y Competitividad” (Institute of Health Carlos III, Ministry of Economy and competitiveness), Spain (FIS PI11-01345). The study was registered in in September 2014 (ref: NCT02245373) ( The first patient was enrolled in June 2013. MRV is grateful to the “Instituto de Salud Carlos III, Ministerio de Economía y Competitividad” for a mobility grant to develop this evaluation. MRV and ASB are grateful to the Strategic Plan for Research and Innovation in Health (Pla Estratègic de Recerca i Innovació en Salut (PERIS) (SLT0002/16/00065; SLT006/17/68). JVL has a “Miguel Servet” research contract from the Institute of Health Carlos III (CP14/00087; Madrid, Spain). We thank the CIBERESP “Centre for Biomedical Research in Epidemiology and Public Health”, the redIAPP “Red de Investigación en Actividades Preventivas y Promoción de la Salud” Research Network Prevention and Health Promotion in Primary Care (RD12/0005/0006 & RD12/0005/0008) and the European Union ERDF funds for its support in the development of this study. We thank Stephen Kelly for help in English editing.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 27 KB)
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Supplementary material 2 (DOCX 18 KB)
10198_2019_1034_MOESM3_ESM.docx (14 kb)
Supplementary material 3 (DOCX 13 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Maria Rubio-Valera
    • 1
    • 2
    • 3
    Email author
  • María Teresa Peñarrubia-María
    • 4
  • Maria Iglesias-González
    • 1
  • Martin Knapp
    • 2
    • 5
  • Paul McCrone
    • 6
  • Marta Roig
    • 1
    • 3
  • Ramón Sabes-Figuera
    • 2
    • 7
  • Juan V. Luciano
    • 1
    • 8
    • 9
  • Juan M. Mendive
    • 8
    • 10
  • Ana Gabriela Murrugara-Centurión
    • 1
    • 8
  • Jordi Alonso
    • 2
    • 11
    • 12
  • Antoni Serrano-Blanco
    • 1
    • 2
  1. 1.Research and Development UnitParc Sanitari Sant Joan de DéuSant Boi de LlobregatSpain
  2. 2.Centre for Biomedical Research in Epidemiology and Public HealthCIBERESPMadridSpain
  3. 3.Department Pharmacology, Toxicology and Therapeutic Chemistry, School of PharmacyUniversitat de BarcelonaBarcelonaSpain
  4. 4.Primary Care Health Centre Bartomeu Fabrés Anglada, Servei d’Atenció Primària Delta Llobregat, Àmbit Costa de PonentInstitut Català de la SalutGavàSpain
  5. 5.Personal Social Services Research UnitLondon School of Economics and Political ScienceLondonUK
  6. 6.Institute of PsychiatryKing’s College LondonLondonUK
  7. 7.Faculty of Economic and Business SciencesUniversitat Pompeu FabraBarcelonaSpain
  8. 8.Primary Care Prevention and Health Promotion Research Network (RedIAPP)BarcelonaSpain
  9. 9.Open University of Catalonia (UOC)BarcelonaSpain
  10. 10.La Mina Primary Care CentreInstitut Català de la SalutBarcelonaSpain
  11. 11.Health Services Research UnitIMIM-Hospital del Mar Medical Research InstituteBarcelonaSpain
  12. 12.Department Experimental and Health SciencesPompeu Fabra University (UPF)BarcelonaSpain

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