Leveraging genetics to enhance the efficacy of PTSD pharmacotherapies

Progress in PTSD pharmacotherapy has lagged far behind that of other major mental illnesses. Unfortunately, due to the enormous costs and lengthy process involved in bringing drugs to market, delivering new treatments to patients with PTSD in the near future will remain a challenge. However, by capitalizing on recent advances in the pharmacogenetics of antidepressants, precision psychiatry approaches can be leveraged to optimize the delivery of currently-available medications in a fraction of the time and cost required to develop novel therapeutics. This paper provides a review of the pharmacogenetics of the four serotonin reuptake inhibitors (SRIs) that are currently endorsed for the treatment of PTSD (paroxetine, sertraline, fluoxetine and venlafaxine). It focuses on genes involved in SRI pharmacokinetics (including the liver enzyme genes CYP2D6 and CYP2C19 and blood-brain barrier-relevant gene ABCB1) as well as those implicated in both SRI pharmacodynamics and the pathophysiology of PTSD and related conditions (e.g., BDNF, FKBP5, HTR1A, HTR2A, TPH2). The review concludes with an overview of emerging commercial platforms for pharmacogenetic-guided prescription and a discussion of challenges and directions for future pharmacogenetic research on PTSD.