The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides recommendations on dosing of amitriptyline and nortriptyline based on patients’ genotype (UM, EM, PM) for CYP2D6 and CYP2C19 isoenzymes.29,30 Pharmacodynamically, several SNPs have been associated with treatment-emergent side effects. SNPs in MDGA2 and 5-HT2A receptor genes were associated with higher rates of sexual dysfunction among Asian patients.31,32

In CGASs, German patients who were T carriers of the tryptophan hydroxylase (TPH2) gene had 3.5 times the rate of treatment-emergent suicidal ideation from treatment with antidepressants.33 By identifying potential adverse effects before treatment initiation, pharmacogenomics testing may improve medication adherence.


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Several investigations have demonstrated the potential utility and benefit of pharmacogenomic testing in clinical settings. Hall-Flavin et al compared antidepressant response and remission rates between genetically-guided prescribing and usual care in 227 patients.34 The GeneSight® interpretive report provides prescribers with three levels of recommendations for prescribers (‘use as directed’, ‘use with caution’, and ‘use with increased caution and with more frequent monitoring’).

Patients who received antidepressants based on genetically-guided interpretive reports provided to prescribers had greater response rates and remission after 8 weeks.34 In a retrospective study, patients with MDD who were identified to require monitoring based on their pharmacogenomic testing reports (completed post-hoc) had greater number of medical visits, higher total healthcare costs, greater number of missed days from work and greater number of disability claims compared to those who did not have variations in CYP450 enzymes (CYP2D6, CYP2C19, CYP2C9, CYP1A2).35

Patients with severe mental illness with PM or UM profiles for CYP2D6 enzyme have incurred longer hospitalization stays amounting to $4,000-$6,000.36 Cost-effectiveness studies have shown that pharmacogenomic testing can reduce average cost/resource utilization by 10% to 30%.27, 35-38

Barriers to Implementing Routine Pharmacogenetic Testing

There is sufficient evidence that certain genetic variants play a role in determining response and remission to antidepressants and development or worsening of adverse effects.

There is also increasing evidence that gene-environment interactions play a role in treatment response and disease remission but methodological challenges exist to study such interactions.33,34

The utility of pharmacogenetic testing in routine psychiatric practice is unclear, and currently there is no recommendation to conduct testing prior to initiating antidepressant treatment.39

Before widespread implementation and use of pharmacogenomic testing for antidepressants, several barriers must be overcome such as limited accessibility of cost-effective tests, adequate and timely clinical decision support for prescribers, and trained personnel to provide appropriate education to patients.  

Kelly C. Lee, PharmD, MAS, BCPP, is an associate professor of clinical pharmacy at the University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences. 

References

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