Pharmacogenomics of Suicidal Events

Abstract

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.

Importance of genomic studies for drug withdrawal with mental toxicities

“…10 Last but not least, more and more genetic markers and alleles have been found to link with suicidal ideations and behaviors in clinics. [11][12][13][14][15][16][17][18][19] The literature has shown this relation in drugs with mental toxicities. However, these are direct evidence which fully support the relationship between human's genetic features and drug toxicities.…”

“…Extant pharmacogenomic studies of increases in suicidal ideation and behavior in antidepressant-treated depressed patients report associations with polymorphisms in genes involved in at least 9 related genes, including transcription (CREB1), neuroprotection (BDNF, NTRK2), glutamatergic and noradrenergic neurotransmission (GRIA3, GRIK2, ADRA2A), stress and inflammatory response (FKBP5, IL28RA) and synthesis of glycoproteins (PAPLN). 17 These large volumes of polymorphism of genetic markers will greatly affect the quality and fairness of drug assessment and approval or withdraw. Thus we must pay special attention to it.…”

Genetics in Suicide Treatments, Modern Diagnosis Establishments

“…Genetic panels affecting both drug-active and drug-toxic genes (molecules) in the same times might be optimal avenues for in-depth scientific investigations [9][10][11][12][13][14][15][16]. Other current achievements relating antidepressant drug therapies are offered in Table 1.…”

A patient-centered model of the action of psychotropic drugs

“…Pharmacogenomic findings have also helped to elucidate some of the possible mechanisms that underlie behavioural toxicity. Thus, variations in FKBP5, a gene linked to glucocorticoid receptor sensitivity, are apparently associated with suicidal events in adolescents taking an antidepressant [48]; other genes have also been implicated in antidepressant-related suicidal events [49]. For a less dramatic example, it is well-known that some patients taking atypical antipsychotics develop symptoms of OCD; a recent association has been found between SLC1A1, a glutamate transporter gene, and the development of this behavioural adverse effect [50].…”