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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

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

Depression/mood disorder Antidepressant medication Primary care Health economics 

Notes

Acknowledgements

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 ClinicalTrials.gov in September 2014 (ref: NCT02245373) (https://clinicaltrials.gov/ct2/show/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

10198_2019_1034_MOESM1_ESM.docx (28 kb)
Supplementary material 1 (DOCX 27 KB)
10198_2019_1034_MOESM2_ESM.docx (18 kb)
Supplementary material 2 (DOCX 18 KB)
10198_2019_1034_MOESM3_ESM.docx (14 kb)
Supplementary material 3 (DOCX 13 KB)

References

  1. 1.
    Anderson, I., Pilling, S., Barnes, A., Bayliss, L., Bird, V., Burbeck, R., Chew-Graham, C., Clarke, J., Dyer, M., Flanagan, E., Harris, C., Hopkins, S., Kenwright, M., Kuyken, W., Lewis, A., Lewis, G., Li, R., Masterson, B., Meader, N., Meudell, A., Mitch, J.: Depression in adults: recognition and management. NICE Clinical Guideline CG90 (2009)Google Scholar
  2. 2.
    Departament de Salut: [Adaptació al model sanitari català de la guia de pràctica clínica sobre el maneig de la depressió major en l’adult]., Barcelona: Agència d’Informació, Avaluació i Qualitat en Salut. Pla director de salut mental i addictions: (2010)Google Scholar
  3. 3.
    King, M., Nazareth, I., Levy, G., Walker, C., Morris, R., Weich, S., Bellón-Saameño, J.A., Moreno, B., Svab, I., Rotar, D., Rifel, J., Maaroos, H.-I., Aluoja, A., Kalda, R., Neeleman, J., Geerlings, M.I., Xavier, M., de Almeida, M.C., Correa, B., Torres-Gonzalez, F.: Prevalence of common mental disorders in general practice attendees across Europe. Br. J. Psychiatry. 192, 362–367 (2008).  https://doi.org/10.1192/bjp.bp.107.039966 CrossRefGoogle Scholar
  4. 4.
    Serrano-Blanco, A., Palao, D.J., Luciano, J.V., Pinto-Meza, A., Luján, L., Fernández, A., Roura, P., Bertsch, J., Mercader, M., Haro, J.M.: Prevalence of mental disorders in primary care: results from the diagnosis and treatment of mental disorders in primary care study (DASMAP). Soc. Psychiatry Psychiatr. Epidemiol. 45, 201–210 (2010)CrossRefGoogle Scholar
  5. 5.
    Hegel, M.T., Oxman, T.E., Hull, J.G., Swain, K., Swick, H.: Watchful waiting for minor depression in primary care: remission rates and predictors of improvement. Gen. Hosp. Psychiatry. 28, 205–212 (2006)CrossRefGoogle Scholar
  6. 6.
    Fournier, J.C., DeRubeis, R.J., Hollon, S.D., Dimidjian, S., Amsterdam, J.D., Shelton, R.C., Fawcett, J.: Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 303, 47–53 (2010)CrossRefGoogle Scholar
  7. 7.
    Fernández, A., Rubio-Valera, M., Bellón, J., Pinto-Meza, A., Luciano, J.V., Mendive, J.M., Haro, J.M., Palao, D.J., Serrano-Blanco, A.: Recognition of anxiety disorders by the general practitioner: results from the DASMAP study. Gen. Hosp. Psychiatry. 34, 227–233 (2012).  https://doi.org/10.1016/j.genhosppsych.2012.01.012 CrossRefGoogle Scholar
  8. 8.
    Fernández, A., Pinto-Meza, A., Bellón, J.A., Roura-Poch, P., Haro, J.M., Autonell, J., Palao, D.J., Peñarrubia, M.T., Fernández, R., Blanco, E., Luciano, J.V., Serrano-Blanco, A.: Is major depression adequately diagnosed and treated by general practitioners? Results from an epidemiological study. Gen. Hosp. Psychiatry. 32, 201–209 (2010)CrossRefGoogle Scholar
  9. 9.
    Rubio-valera, M., Fernández, A., Luciano, J.V., Hughes, C.M., Pinto-meza, A., Moreno-küstner, B., Palao, D.J., Haro, J.M., Serrano-blanco, A.: Psychotropic prescribing in catalonia: results from an epidemiological study. Fam. Pract. 29, 154–162 (2012)CrossRefGoogle Scholar
  10. 10.
    Meredith, L.S., Cheng, W.J.Y., Hickey, S.C., Dwight-Johnson, M.: Factors associated with primary care clinicians’ choice of a watchful waiting approach to managing depression. Psychiatr. Serv. 58, 72–78 (2007)CrossRefGoogle Scholar
  11. 11.
    Iglesias-González, M., Aznar-Lou, I., Gil-Girbau, M., Moreno-Peral, P., Peñarrubia-María, M.T., Rubio-Valera, M., Serrano-Blanco, A.: Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild–moderate depression in primary care: a systematic review. Fam. Pract. 34, 639–648 (2017).  https://doi.org/10.1093/fampra/cmx054 CrossRefGoogle Scholar
  12. 12.
    Bosmans, J.E., Hermens, M.L.M., de Bruijne, M.C., van Hout, H.P.J., Terluin, B., Bouter, L.M., Stalman, W.A.B., van Tulder, M.W.: Cost-effectiveness of usual general practitioner care with or without antidepressant medication for patients with minor or mild-major depression. J. Affect. Disord. 111, 106–112 (2008)CrossRefGoogle Scholar
  13. 13.
    Kendrick, T., Chatwin, J., Dowrick, C., Tylee, A., Morriss, R., Peveler, R., Leese, M., McCrone, P., Harris, T., Moore, M., Byng, R., Brown, G., Barthel, S., Mander, H., Ring, A., Kelly, V., Wallace, V., Gabbay, M., Craig, T., Mann, A.: Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care. Health Technol. Assess. 13, iii–iv (2009).  https://doi.org/10.3310/hta13220 (ix–xi, 1–159) CrossRefGoogle Scholar
  14. 14.
    Rubio-Valera, M., Beneitez, I., Penarrubia-Maria, M.T., Luciano, J.V., Mendive, J.M., McCrone, P., Knapp, M., Sabes-Figuera, R., Kocyan, K., Garcia-Campayo, J., Serrano-Blanco, A.: Cost-effectiveness of active monitoring versus antidepressants for major depression in primary health care: a 12-month non-randomized controlled trial (INFAP study). BMC Psychiatry. 15, 63 (2015).  https://doi.org/10.1186/s12888-015-0448-3 CrossRefGoogle Scholar
  15. 15.
    Mira, J.J., Llinás, G., Gil, V., Orozco, D., Palazón, I., Vitaller, J.: Validation of an instrument for identifying styles of the professional practice of the primary care doctor. Aten. Primaria. 21, 14–22 (1998)Google Scholar
  16. 16.
    Chisholm, D., Knapp, M.R.J., Knudsen, H.C., Amaddeo, A., Gaite, L., Van Wijngaarden, B.: Client socio-demographic and service receipt inventory—European version: Development of an instrument for international research. EPSILON study 5. Br. J. Psychiatry. 177, s28–s33 (2000)CrossRefGoogle Scholar
  17. 17.
    Spanish National Institute of Statistics: minimum wage survey. http://www.ine.es. Accessed 22 June 2017
  18. 18.
    Badia, X., Schiaffino, A., Alonso, J., Herdman, M.: Using the EuroQol 5-D in the Catalan general population: feasibility and construct validity. Qual. Life Res. 7, 311–322 (1998)CrossRefGoogle Scholar
  19. 19.
    EuroQol Group: EuroQol-a new facility for the measurement of health-related quality of life. Health Policy 16, 199–208 (1990)CrossRefGoogle Scholar
  20. 20.
    Glick, H., Doshi, J., Sonrad, S.: Economic Evaluation in Clinical Trials. Oxford University Press: Oxford (2014)CrossRefGoogle Scholar
  21. 21.
    Diez-Quevedo, C., Rangil, T., Sanchez-Planell, L., Kroenke, K., Spitzer, R.L.: Validation and utility of the patient health questionnaire in diagnosing mental disorders in 1003 general hospital Spanish inpatients. Psychosom. Med. 63, 679–686 (2001)CrossRefGoogle Scholar
  22. 22.
    Kroenke, K., Spitzer, R.L., Williams, J.B.W.: The PHQ-9: validity of a brief depression severity measure. J. Gen. Intern. Med. 16, 606–613 (2001)CrossRefGoogle Scholar
  23. 23.
    Spitzer, R.L., Kroenke, K., Williams, J.B.: Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary care evaluation of mental disorders. Patient Health Questionnaire. JAMA. 282, 1737–1744 (1999)CrossRefGoogle Scholar
  24. 24.
    First, M.B., et, Spitzer, R.L., Gibbon, M., Williams, J.B.W.: Structured clinical interview for DSM-IV axis I disorders, clinician version (SCID-CV). American Psychiatric Publishing Inc (1997)Google Scholar
  25. 25.
    Mitra, R., Reiter, J.P.: A comparison of two methods of estimating propensity scores after multiple imputation. Stat. Methods Med. Res. 25, 188–204 (2016).  https://doi.org/10.1177/0962280212445945 CrossRefGoogle Scholar
  26. 26.
    Rubio-Valera, M., Serrano-Blanco, A., Magdalena-Belío, J., Fernández, A., García-Campayo, J., Pujol, M.M., Hoyo, Y.L., Del: Effectiveness of pharmacist care in the improvement of adherence to antidepressants: a systematic review and meta-analysis. Ann. Pharmacother. 45, 39–48 (2011)CrossRefGoogle Scholar
  27. 27.
    Serrano-Blanco, A., Pinto-Meza, A., Suárez, D., Peñarrubia, M.T., Haro, J.M.: Cost–utility of selective serotonin reuptake inhibitors for depression in primary care in Catalonia. Acta Psychiatr. Scand. Suppl. 114, 39–47 (2006).  https://doi.org/10.1111/j.1600-0447.2006.00918.x CrossRefGoogle Scholar
  28. 28.
    Rubio-Valera, M., Bosmans, J., Fernández, A., Peñarrubia-María, M., March, M., Travé, P., Bellón, J., Serrano-Blanco, A.: Cost-effectiveness of a community pharmacist intervention in patients with depression: a randomized controlled trial (PRODEFAR Study). PLoS One. 8, e70588 (2013).  https://doi.org/10.1371/journal.pone.0070588 CrossRefGoogle Scholar
  29. 29.
    Hermens, M.L., van Hout, H.P., Terluin, B., Adèr, H.J., Penninx, B.W., van Marwijk,H.W., Bosmans, J.E., van Dyck, R., de Haan, M., Katon, W., Schulberg, H., Ackermann,R., Williams, J., Doogan, D., Langdon, C., Elkin, I., Shea, M., Watkins, J., Imber,S., Sotsky, S., Collins, J., Glass, D., Pilkonis, P., Leber, W., Docherty, J., Middleton,H., Shaw, I., Hull, S., Feder, G., Oxman, T., Sengupta, A., Waal, M. De, Stolk, J.,Marwijk, H. van, Springer, M., Spies, T., Mokkink, H., Robbé, P.D.V., Grol, R., Marwijk,H. Van, Grundmeijer, H., Brueren, M., Sigling, H., Stolk, J., Gelderen, M. Van, Vintges,M., Eizenga, W., Burgers, J., Marwijk, H. Van, Bijl, D., Ader, H., Haan, M. De, MacGillivray,S., Arroll, B., Hatcher, S., Ogston, S., Reid, I., Sullivan, F., Williams, B., Crombie,I., Brugha, T., Cragg, D., Costa, P., McCrae, R., Andrews, G., Peters, L., Montgomery,S., Asberg, M., Hermens, M., Adèr, H., Hout, H. van, Terluin, B., Dyck, R. van, Haan,M. de, Ware, J., Sherbourne, C., Ware, J., Koshinski, M., Keller, S., Larsen, D.,Attkisson, C., Hargreaves, W., Nguyen, T., Malt, U., Robak, O., Madsbu, H., Bakke,O., Loeb, M., Cohen, J., Jones, B., Jarvis, P., Lewis, J., Ebbutt, A., Rasbash, J.,Browne, W., Goldstein, H., Yang, M., Woodhouse, G., Healy, M., Hauck, W., Anderson,S., Schaik, D. van, Klijn, A., Hout, H. van, Marwijk, H. van, Beekman, A., Haan, M.De, Dyck, R. van, Piaggio, G., Elbourne, D., Altman, D., Pocock, S., Evans, S., Barrett,J., Williams, J., Oxman, T., Frank, E., Katon, W., Sullivan, M., Hegel, M., Cornell,J., Sengupta, A., Paykel, E., Hollyman, J., Freeling, P., Sedgwick, P., Bedi, N.,Chilvers, C., Churchill, R., Dewey, M., Duggan, C., Fielding, K., Gretton, V., Miller,P., Harrison, G., Lee, A., Williams, I., Chilvers, C., Dewey, M., Fielding, K., Gretton,V., Miller, P., Palmer, B., Weller, D., Churchill, R., Williams, I., Bedi, N., Duggan,C., Lee, A., Harrison, G., Mynors-Wallis, L., Gath, D., Day, A., Baker, F., Marwijk,H. van: Clinical effectiveness of usual care with or without antidepressant medication for primary care patients with minor or mild-major depression: a randomized equivalence trial. BMC Med. 5, 36 (2007).  https://doi.org/10.1186/1741-7015-5-36
  30. 30.
    van Straten, A., Hill, J., Richards, D.A., Cuijpers, P.: Stepped care treatment delivery for depression: a systematic review and meta-analysis. Psychol. Med. 45, 231–246 (2015).  https://doi.org/10.1017/S0033291714000701 CrossRefGoogle Scholar
  31. 31.
    Posternak, M.A., Miller, I.: Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups. J. Affect. Disord. 66, 139–146 (2001)CrossRefGoogle Scholar
  32. 32.
    Vallejo-Torres, L., García-Lorenzo, B., Castilla, I., Valcárcel Nazco, C., García-Pérez, L., Linertová, R., Serrano-Aguilar, P.: Valor Monetario de un Año de Vida Ajustado por Calidad: Estimación empírica del coste de oportunidad en el Sistema Nacional de Salud. Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad. Santa Cruz de Tenerife: Servicio Canario de la Salud. Serie: Informes de Evaluación de Tecnologías Sanitarias SESCS (2015)Google Scholar
  33. 33.
    Shiroiwa, T., Sung, Y.-K., Fukuda, T., Lang, H.-C., Bae, S.-C., Tsutani, K.: International survey on willingness-to-pay (WTP) for one additional QALY gained: what is the threshold of cost effectiveness? Health Econ. 19, 422–437 (2010).  https://doi.org/10.1002/hec.1481 CrossRefGoogle Scholar
  34. 34.
    Barbosa, C., Cowell, A., Dowd, W., Landwehr, J., Aldridge, A., Bray, J.: The cost-effectiveness of brief intervention versus brief treatment of Screening, Brief Intervention and Referral to Treatment (SBIRT) in the United States. Addiction. 112, 73–81 (2017).  https://doi.org/10.1111/add.13658 CrossRefGoogle Scholar
  35. 35.
    MacNeil Vroomen, J., Bosmans, J.E., Eekhout, I., Joling, K.J., van Mierlo, L.D., Meiland, F.J.M., van Hout, H.P.J., de Rooij, S.E.: The cost-effectiveness of two forms of case management compared to a control group for persons with dementia and their informal caregivers from a societal perspective. PLoS One. 11, e0160908 (2016).  https://doi.org/10.1371/journal.pone.0160908 CrossRefGoogle Scholar
  36. 36.
    Scherrer, J.F., Salas, J., Schneider, F.D., Bucholz, K.K., Sullivan, M.D., Copeland, L.A., Ahmedani, B.K., Burroughs, T., Lustman, P.J.: Characteristics of new depression diagnoses in patients with and without prior chronic opioid use. J. Affect. Disord. 210, 125–129 (2017).  https://doi.org/10.1016/j.jad.2016.12.027 CrossRefGoogle Scholar
  37. 37.
    Lutz, W., Schiefele, A.-K., Wucherpfennig, F., Rubel, J., Stulz, N.: Clinical effectiveness of cognitive behavioral therapy for depression in routine care: a propensity score based comparison between randomized controlled trials and clinical practice. J. Affect. Disord. 189, 150–158 (2016).  https://doi.org/10.1016/j.jad.2015.08.072 CrossRefGoogle Scholar
  38. 38.
    Vuorilehto, M.S., Melartin, T.K., Riihimäki, K., Isometsä, E.T.: Pharmacological and psychosocial treatment of depression in primary care: low intensity and poor adherence and continuity. J. Affect. Disord. 202, 145–152 (2016).  https://doi.org/10.1016/j.jad.2016.05.035 CrossRefGoogle Scholar
  39. 39.
    Rubio-Valera, M., March Pujol, M., Fernández, A., Peñarrubia-María, M.T., Travé, P., López Del Hoyo, Y., Serrano-Blanco, A.: Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial. Eur. Neuropsychopharmacol. 23, 1057–1066 (2013).  https://doi.org/10.1016/j.euroneuro.2012.11.006 CrossRefGoogle Scholar

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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