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. 2011;13(1):63-71.
doi: 10.31887/DCNS.2011.13.1/jlicinio.

Pharmacogenomics of antidepressant treatment effects

Julio Licinio  1 , Ma-Li Wong
Affiliations

Pharmacogenomics of antidepressant treatment effects

Julio Licinio et al. Dialogues Clin Neurosci. 2011.

Abstract
in English, Spanish, French

There has been considerable promise and hope that pharmacogenomics will optimize existing treatments for major depression, as well as identify novel targets for drug discovery. Immediately after the sequencing of the human genome, there was much hope that tremendous progress in pharmacogenomics would rapidly be achieved. In the past 10 years this initial enthusiasm has been replaced by a more sober optimism, as we have gone a long way towards the goal of guiding therapeutics based on genomics. While the effort to translate discovery to clinical applications is ongoing, we now have a vast body of knowledge as well as a clear direction forward. This article will provide a critical appraisal of the state of the art in the pharmacogenomics of depression, both in terms of pharmacodynamics and pharmacokinetics.

Han sido considerables las promesas y esperanzas respecto a que la farmacogenómica pudiera optimizar los tratamientos existentes para la depresión mayor, así como identificar nuevos blancos para el descubrimiento de fármacos. Inmediatamente después de la secuenciación del genoma humano hubo grandes esperanzas en que rápidamente se alcanzaría un tremendo progreso en la farmacogenómica. En los últimos diez años este entusiasmo inicial fue reemplazado por un prudente optimismo y se ha recorrido un largo camino hacia el objetivo de guiar la terapéutica en base a la genómica. Así como se sigue progresando en el esfuerzo por traducir los descubrimientos en aplicaciones clínicas sigue progresando y actualmente se cuenta con un gran conjunto de conocimientos así como una clara dirección a futuro. Este artículo entregará una evaluación crítica del estado del arte en la farmacogenómica de la depresión, tanto en términos farmacodinámicos como farmacocinéticos.

La pharmacogénomique a soulevé promesses et espoirs considérables d'optimiser les traitements existants de la dépression majeure et de trouver de nouvelles cibles pour la recherche pharmaceutique. Le séquençage du génome humain a été immédiatement suivi d'espoirs sans précédents de progrès rapides en pharmacogénomique. Cet enthousiasme a été remplacé ces 10 dernières années par un optimisme modéré, bien que nous ayons parcouru un long chemin vers les recommandations thérapeutiques basées sur la génomique. La traduction des découvertes en applications cliniques est en cours et nous disposons maintenant de connaissances élargies et de perspectives claires. Cet article propose une évaluation critique de l'état de l'art sur la pharmacogénomique de la dépression, à la fois en termes de pharmacodynamique et de pharmacocinétique.

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Figures

Figure 1.
Figure 1.. CYP2D6-mediated quantitative influences on pharmacokinetics of antidepressant drugs expressed as percent dose adjustments: CYP2D6 poor metabolizers (PM, white), intermediate metabolizers (IM, gray), extensive metabolizers (EM, dark gray), ultrarapid metabolizers (UM, black) Dose adjustments were calculated according to the data given in Table II. If data on active drug moiety (consisting on active principle metaboite+parent drug of active enantiomers of a racemic drug) were given, dose recommendations were based on these data only (other studies not providing so detailed information were not incorporated). If more than one study was integrated, the weighted mean for the dose adjustment was taken according to the number of poor metabolizers in each study. Data on mirtazapine, moclobemide, fluoxetine, and maprotiline were not shown in the figure, since no dose adjustment based on CYP2D6 can be recommended at present. Reproduced from ref 43: Kirchheiner J, Nickchen K, Bauer M, et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004;9:442-473. Copyright © Nature Publishing Group 2004
Figure 2.
Figure 2.. CYP2C19-mediated quantitative influences on pharmacokinetics of antidepressant drugs expressed as percentage dose adaptations: CYP2C19 poor metabolizers (PM, white), intermediate metabolizers (IM, gray), extensive metabolizers (EM, dark gray). Reproduced from ref 43: Kirchheiner J, Nickchen K, Bauer M, et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004;9:442-473. Copyright © Nature Publishing Group 2004
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