Curators' Favorite Papers

The first paper, by A. Ahmed et al. in the journal Clinical Pharmacology and Therapeutics (Benefits of and Barriers to Pharmacogenomics-Guided Treatment for Major Depressive Disorder), discusses pharmacogenetic (PGx) testing in the context of depression. In a pilot study, 1,002 out of 1,013 (99%) subjects had an actionable variant in CYP2D6, CYP2C9, CYP2C19, SLCO1B1 or VKORC1. With regards to anti-depressants, 79% of subjects had actionable variants in CYP2D6 (metabolizes fluoxetine, paroxetine, nortriptyline, and desipramine), 60% in CYP2C19 (metabolizes citalopram and escitalopram) and 36% in CYP2C9 (metabolizes fluoxetine). The authors posit that wider implementation will still require several steps going forward. In addition to making PGx testing pre-emptive, so that genotype information is already present in patient electronic health records (EHRs), physicians will need to be convinced of the clinical utility of PGx testing for patients with mood disorders.  The authors believe this means generating data from larger studies “conducted by disinterested groups”, studies in adolescents, studies investigating multiple genes and the inclusion of metabolomics to inform genomics.

The second paper by Maciel et al. in the journal Neuropsychiatric Disease Treatment (Estimating Cost Savings of Pharmacogenetic Testing for Depression in Real-World Clinical Settings) describes potential cost-savings associated with pharmacogenetic (PGx) testing in patients with depression. The researchers estimated a one-time cost of USD $2,000 for PGx testing and used a published cost-calculator to estimate cost-savings. Data were from a published double-blind, multi-center, randomized clinical trial of 685 adults who had been diagnosed with depression or anxiety. Patients were randomized to PGx-guided treatment or standard of care (control). The study found that those subjects randomized to PGx-guided dosing and prescribing had significant improvements in clinical outcomes as compared to the control group. Using these data, the study calculated that the cost savings for PGx-testing vs standard of care for patients with depression or anxiety totaled USD $3,962 per year after accounting for the one-time cost of PGx testing.

A new meta-analysis of 522 studies that was recently published in The Lancet concluded that at minimum, short-term treatment with anti-depressants was more effective than placebos in treating acute depression. The study made headlines in major media-outlets and found that some anti-depressants worked better than others, which may lead to more interest in PGx-guided dosing.

You can find PGx-guided drug dosing guidelines from the Clinical Pharmacogenetic Implementation Consortium (CPIC) for tricyclic anti-depressants and selective serotonin re-uptake inhibitors on cpicpgx.org. You may also find more information about the following genes and drugs on PharmGKB:

Genes
CYP2D6
CYP2C9
CYP2C19

Drugs
fluoxetine
paroxetine
nortriptyline
desipramine
citalopram
escitalopram
amitriptyline
fluoxetine