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Open Access Research article

Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants

Ali A Alkhafaji12, Ludovic Trinquart1234, Gabriel Baron12, Moïse Desvarieux256 and Philippe Ravaud123456*

Author affiliations

1 Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, 1 place du parvis Notre Dame, Paris, 75004, France

2 INSERM U738, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, 1 place du parvis Notre Dame, Paris, 75004, France

3 Université Paris Descartes - Sorbonne Paris Cité, 12 Rue de l'École de Médecine Paris, 75006, France

4 French Cochrane Centre, Hôpital Hôtel-Dieu, 1 place du parvis Notre Dame, Paris, 75004, France

5 EHESP School of Public Health, Avenue du Professeur Léon-Bernard, CS 74312, Rennes, 35043, France

6 Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168th Street, New York, NY 10032, USA

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Citation and License

BMC Medicine 2012, 10:142  doi:10.1186/1741-7015-10-142

Published: 20 November 2012

Abstract

Background

"Evergreening" refers to the numerous strategies whereby owners of pharmaceutical products use patent laws and minor drug modifications to extend their monopoly privileges on the drug. We aimed to evaluate the impact of evergreening through the case study of the antidepressant citalopram and its chiral switch form escitalopram by evaluating treatment efficacy and acceptability for patients, as well as health insurance costs for society.

Methods

To assess efficacy and acceptability, we performed meta-analyses for efficacy and acceptability. We compared direct evidence (meta-analysis of results of head-to-head trials) and indirect evidence (adjusted indirect comparison of results of placebo-controlled trials). To assess health insurance costs, we analyzed individual reimbursement data from a representative sample of the French National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to 2010, which allowed for projecting these results to the whole SNIIR-AM population (53 million people).

Results

In the meta-analysis of seven head-to-head trials (2,174 patients), efficacy was significantly better for escitalopram than citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to 2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12 escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively, efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to 1.30)). Because of the discrepancy, we could not combine direct and indirect data (test of inconsistency, P = 0.07). A similar discrepancy was found for treatment acceptability. The overall reimbursement cost burden for the citalopram, escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8 million Euros for escitalopram.

Conclusions

The clinical benefit of escitalopram versus citalopram remains uncertain. In our case of evergreening, escitalopram represented a substantially high proportion of the overall reimbursement cost burden as compared with citalopram and the generic forms.

Keywords:
Evergreening; Meta-analysis; Health Insurance Reimbursement; Escitalopram; Citalopram; Chiral switch; French health information system; generic drugs