Pharmacogenetics may inform an accurate prescribing of antidepressants by identifying the genetic background specifically responding to a certain drug. Despite decades of efforts though, pharmacogenetics appears to be still in its infancy.

A clearer understanding of the pharmacodynamics and pharmacokinetics events in combination with the genetic and epigenetic controls of cells and molecular cascade must inform the future of personalised medicine.

To systematically review the current cutting edge knowledge about pharmacognetics in the search for the next groundbreaking biological key events that may provide the keys to future treatments.

The major online databases are systematically searched with common keywords by two independent researchers and conflicting findings are solved during regular meetings dedicated to the topic in object. Manual searching of single bibliographies is also put in place.

Genes belonging to the serotoningeric, dopaminergic, glutamatergic and GABAergic systems are classic candidates for pharmacogenetics whose role was not confirmed by GWAS analyses, which, on the other hand, identified genes related to molecular pathways not associated with direct target of drugs used for the treatment of depression.

Both hypothesis driven candidate genetic investigations and GWAS analyses have been conducted so far, leading to the identification of a handful of potential good candidates, but the replication rate of the positive association findings lags behind expectations. The current knowledge about the pharmacodyncamic and pharmacokinetic genetic determinants of antidepressant response is critically analysed and new candidates are presented discussed.