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The serotonin transporter 5-HTTLPR polymorphism moderates response to SSRIs and side-effect burden. The aim of this study is to quantify the cost-utility of incorporating 5-HTTLPR genotyping in drug treatment of major depressive disorder (MDD). We previously reported a theoretical model to simulate antidepressant treatment with citalopram or bupropion for 12 weeks. The drugs were alternatively selected according to an 'as usual' algorithm or based on response and tolerability predicted by 5-HTTLPR profile. Here we apply this model to conduct a cost-utility analysis in three European regions with high GDP (Euro A), middle GDP (Euro B) and middle-high GDP (Euro C). In addition we test a verification scenario in which citalopram+bupropion augmentation is administered to individuals with the least favorable 5-HTTLPR genotype. Treatment outcomes are remission and Quality Adjusted-Life Weeks (QALW). Cost data (international $, year 2009) are retrieved from the World Health Organization (WHO) and national official sources. In base-case scenario incremental cost-effectiveness ratio (ICER) values are $1147 (Euro A), $1185 (Euro B) and $1178 (Euro C). From cost-effectiveness acceptability curve (CEAC), the probability of having an ICER value below WHO recommended cost-utility threshold (3 GDP per capita=$1926) is >90% in high-income countries (Euro A). In middle- income regions, these probabilities are <30% (Euro B) and <55% (Euro C) respectively. All estimates are robust against variations in treatment parameters, but if genetic test cost decreases to $100, pharmacogenetic approach becomes cost-effective in middle-income countries (Euro B). This simulation using data from 27 European states suggests that choosing antidepressant treatment from the results of 5-HTTLPR might be a cost-effective solution in high income countries. Its feasibility in middle income countries needs further research., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the benefit of pharmacogenetics in antidepressant treatment., Methods: In a simulated trial 100,000 subjects in a current episode of major depressive disorder (MDD) received citalopram or bupropion based on the clinician's decision (algorithm A) or following indications from 5-HTTLPR genetic testing (algorithm B), which effect size of was estimated from a meta-analysis of pharmacogenetic trials. A and B were compared in a cost-utility analysis (12 weeks). Costs (international $, 2010) were drawn from official sources. Treatment effects were expressed as quality-adjusted life weeks (QALWs). Outcome was incremental cost-effectiveness ratio (ICER)., Results: Under base-case conditions, genetic test use was associated with increases in antidepressant response (0.062 QALWs) and tolerability (0.016 QALWs) but cost benefit was not acceptable (ICER = $2,890; $1,800-$4,091). However, when the joint effect on antidepressant response and tolerability was analyzed in two recurrent episodes, ICER dropped to $1,392 ($837-$1,982). Cost-effectiveness acceptability curve (CEAC) showed a >80% probability that ICER value fell below the commonly accepted 3 times Gross Domestic Product (GDP) threshold (World Health Organization) and therefore suggesting cost-effectiveness., Conclusion: Notwithstanding some caveats (exclusion of gene-gene and gene-environment interactions; simple 5-HTTLPR architecture), this simulation is favourable to incorporate pharmacogenetic test in antidepressant treatment.