Individualized pharmacogenomics for depressive episodes: A narrative review

Area of Science:

• Psychiatric pharmacogenomics
• Precision psychiatry
• Genetics in mental health

Background:

• Major depressive disorder (MDD) and bipolar disorder (BD) have high prevalence and variable treatment responses due to interindividual biological differences.
• Current treatments like antidepressants and antipsychotics often face challenges such as delayed response, adverse drug reactions, and treatment resistance.
• Pharmacogenomics offers a personalized approach by linking genetic variability to drug metabolism and response.

Purpose of the Study:

• To review key pharmacogenes and variants for MDD treatment.
• To distinguish clinically actionable genes from those needing further research.
• To assess the current and future role of pharmacogenomics in precision psychiatry.

Main Methods:

• Synthesized evidence from pharmacogenomic guideline resources (CPIC, PharmGKB, DPWG).
• Focused on pharmacokinetic and pharmacodynamic genes relevant to psychiatric pharmacotherapy.
• Reviewed randomized trials and meta-analyses evaluating pharmacogenomic-guided prescribing.

Main Results:

• CYP2D6 and CYP2C19 have robust evidence for clinical use, improving SSRI outcomes by optimizing drug exposure and reducing side effects.
• CYP3A4 and CYP1A2 influence psychotropic drug metabolism, but guideline recommendations are limited.
• Pharmacodynamic genes (COMT, FKBP5, HTR2A, SLC6A4, MTHFR) and polygenic risk scores show promise but require further validation for routine use.

Conclusions:

• Pharmacogenomic testing is a valuable adjunct to psychiatric care, not a cure.
• Validated pharmacogene testing, guided by established resources, can optimize treatment.
• Continued research into emerging genes and polygenic models is crucial for realizing the full potential of precision psychiatry.