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Do we need pharmacogenetics to personalize antidepressant therapy?

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Abstract

This review examines the role of drug metabolism and drug target polymorphism in determining the clinical response to antidepressants. Even though antidepressants are the most effective available treatment for depressive disorders, there is still substantial need for improvement due to the slow onset of appreciable clinical improvement and the association with side effects. Moreover, a substantial group of patients receiving antidepressant therapy does not achieve remission or fails to respond entirely. Even if the large variation in antidepressant treatment outcome across individuals remains poorly understood, one possible source of this variation in treatment outcome are genetic differences. The review focuses on a few polymorphisms which have been extensively studied, while reporting a more comprehensive reference to the existing literature in table format. It is relatively easy to predict the effect of polymorphisms in drug metabolizing enzymes, such as cytochromes P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19), which may be determined in the clinical context in order to explain or prevent serious adverse effects. The role of target polymorphism, however, is much more difficult to establish and may be more relevant for disease susceptibility and presentation rather than for response to therapy.

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Acknowledgments

The review was written as partially based on the work of the students of 2011 IUSS (Istituto Universitario di Studi Superiori) Course on Pharmacogenetics of the University of Pavia. The partecipating students, who collected various materials on the pharmacogenetics of psychiatric drugs, were: Aitala Becherucci Edoardo, Aloisio Elena, Azzolini Maria, Barone Gisella, Chiodaroli Elena, Conte Marco, Danesi Daniela, Di Lodovico Laura, Gavuzzi Marta, Giorgio Alessandro, Gitto Salvatore, Melotti Dario, Pelizzari Giacomo, Peluso Francesca, Pepe Antonella, Russo Giulia, Schiavi Susanna, and Vegezzi Elisa.

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  1. Department of Drug Sciences (Pharmacology Section), Center of Excellence in Applied Biology, University of Pavia, IUSS-Pavia (Istituto Universitario di Studi Superiori-Pavia), Viale Taramelli 14, 27100, Pavia, Italy

    Cristina Lanni, Marco Racchi & Stefano Govoni

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  1. Cristina Lanni
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  2. Marco Racchi
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Correspondence to Cristina Lanni.

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Lanni, C., Racchi, M. & Govoni, S. Do we need pharmacogenetics to personalize antidepressant therapy?. Cell. Mol. Life Sci. 70, 3327–3340 (2013). https://doi.org/10.1007/s00018-012-1237-5

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  • DOI: https://doi.org/10.1007/s00018-012-1237-5

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