Progress and prospects in pharmacogenetics of antidepressant drugs.
BACKGROUND
Depression is responsible for the most part of the personal and socio-economic burden due to psychiatric disorders. Since antidepressant response clusters in families, pharmacogenetics represents a meaningful tool to provide tailored treatments and improve the prognosis of depression.


METHODS
This review aims to summarize and discuss the pharmacogenetics of antidepressant drugs in major depressive disorder, with a focus on the most replicated genes, genome-wide association studies (GWAS), but also on the findings provided by new and promising analysis methods. In particular, multimarker tests such as pathway analysis and polygenic risk scores increase the power of detecting associations compared to the analysis of individual polymorphisms. Since genetic variants are not necessarily associated with a change in protein level, gene expression studies may provide complementary information to genetic studies. Finally, the pharmacogenetic tests that have been investigated for clinical application are discussed.


CONCLUSIONS
Despite the lack of widespread clinical applications, preliminary results suggest that pharmacogenetics may be useful to guide antidepressant treatment. The US Food and Drug Administration included pharmacogenetic indications in the labeling of several antidepressants. This represented an important official recognition of the clinical relevance of genetic polymorphisms in antidepressant treatment.
a Department of Biomedical and NeuroMotor Sciences , University of Bologna , Bologna , Italy.
Chiara
C
Fabbri
b Department of Biomedical Science, Odontoiatric and Morphological and Functional Images , University of Messina , Messina , Italy.
Concetta
C
Crisafulli
b Department of Biomedical Science, Odontoiatric and Morphological and Functional Images , University of Messina , Messina , Italy.
Marco
M
Calabrò
b Department of Biomedical Science, Odontoiatric and Morphological and Functional Images , University of Messina , Messina , Italy.
Edoardo
E
Spina
a Department of Biomedical and NeuroMotor Sciences , University of Bologna , Bologna , Italy.
Alessandro
A
Serretti
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D017281:Cost of Illness; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011379:Prognosis
D000928:Antidepressive Agents
GWAS; Major depression; antidepressant; gene; pharmacogenomics; polymorphism; tailored treatment