Author(s): David Brent, Nadine Melhem, Gustavo Turecki
Pharmacogenomic studies of antidepressant treatment-emergent suicidal events in depressed patients report associations with polymorphisms in genes involved in transcription (CREB1), neuroprotection (BDNF and NTRK2), glutamatergic and noradrenergic neurotransmission (GRIA3, GRIK2 and ADRA2A), the stress and inflammatory responses (FKBP5 and IL28RA), and the synthesis of glycoproteins (PAPLN). Nearly all of the reported events in these studies were modest one-time increases in suicidal ideation. In 3231 unique subjects across six studies, 424 (13.1%) patients showed increases in suicidal ideation, eight (0.25%) attempted suicide and four (0.12%) completed suicide. Systems related to most of these genes have also been implicated in studies of suicidal behavior irrespective of treatment. Future pharmacogenomic studies should target events that are clinically significant, related clinical phenotypes of response and medication side effects, and biological pathways that are involved in these outcomes in order to improve treatment approaches.