Utilizing Pharmacogenomic (PGx) testing to guide the choice of antidepressant therapy is becoming more common. Gene-drug interactions of first line antidepressants have some of the highest level of evidence in precision medicine. Professional PGx guidelines[i] exist for SSRI’s and other antidepressants as well as information in the Table of FDA Pharmacogenetic Associations[ii]. PGx can be a useful tool in therapeutic decision making as many patients do not respond to their antidepressants or experience side effects.[iii]
PGx testing may be used prior to the initiation of a first-time antidepressant (pre-emptive) to help guide the choice of the antidepressant, or it may be used retroactively after medication(s) have failed.
The below case study highlights the value of PGx in optimizing antidepressant therapy for your patients with behavioral health disorders.
Case Study
HPI: Mike is a 41-year-old Caucasian male with a history of major depression, panic disorder and newly diagnosed OCD. The patient has tried and failed several antidepressants over the past few years. He is reluctant to try medications due to the side effects he has experienced including insomnia, night sweats and worsening anxiety. Patient (Pt) admits (discloses) to reading the drug package insert and stopping medications after a few days to weeks as he believes he is experiencing the side effects listed. His current level of functioning is not acceptable to him. He is not able to maintain employment and has been experiencing panic attacks when he leaves his house. The patient denies suicide ideation but admits he is feeling extremely low and hopeless.
Current medications: alprazolam 0.5 mg q 8 hours prn
Past medications: citalopram, fluoxetine, paroxetine, bupropion (smoking cessation) and venlafaxine
PMH: MDD (Major Depressive Disorder), Panic Disorder, Obsessive Compulsive Disorder (OCD) and Tobacco abuse
Clinical Considerations:
Based on Mike’s diagnosis, failure of at least one antidepressant and available PGx guidance for antidepressants, a recommendation for PGx testing is made. Pt consents to testing via cheek swab.
(One week later) Results review:
| Gene | Phenotype | Clinical implications |
| CYP2B6 | Intermediate Metabolizer (IM) | May have increased exposure (e.g. associated with bupropion) |
| CYP2C19 | Normal metabolizer (NM) | Predict normal exposure levels and adequate concentrations of medications metabolized by this gene. (e.g. citalopram, escitalopram and sertraline) |
| CYP2D6 | Poor metabolizer (PM) | Active drugs converted to inactive metabolite(s) may have increased exposure (i.e., increased risk of side effects). (e.g. paroxetine, fluvoxamine and venlafaxine) |
Plan:
Considerations: Due to his CYP2C19 Normal Metabolizer phenotype and his diagnosis, escitalopram 10 mg daily with plans of titration and counseling with licensed therapist was recommended. By having the PGx results available, it helped reduce the anxiety the patient was feeling over his body’s ability to process medications and greatly improved his adherence. Mike feels reassured using this informed decision to move forward knowing his medication is optimized to his genetics.
Conclusion:
Many factors contribute to drug response and PGx is an important factor to consider. This case
highlights the value PGx can bring to aid in medication optimization and improved adherence in
this case. In addition, PGx results continue to be a source of information for future therapies.[iv]
Bonus update:
4 years later Pt still doing well on above regimen and quality of life has greatly improved. Pt feels fulfilled both professionally and personally.
[i] Bousman, Chad A., et al. “Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants.” Clinical Pharmacology & Therapeutics (2023).
[ii] Table of Pharmacogenetic Associations[(accessed on 29 June 2023)]; Available online: https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations
[iii] Berney P. Dose-response relationship of recent antidepressants in the short-term treatment of depression. Dialogues Clin Neurosci. 2005;7(3):249-62. doi: 10.31887/DCNS.2005.7.3/pberney. PMID: 16156383; PMCID: PMC3181733.
[iv] Haga SB, LaPointe NM. The potential impact of pharmacogenetic testing on medication adherence. Pharmacogenomics J. 2013 Dec;13(6):481-3. doi: 10.1038/tpj.2013.33. Epub 2013 Sep 3. PMID: 23999596; PMCID: PMC3969027.
Julie Ceno-England, MD is a board-certified family medicine physician with more than 15 years of clinical practice experience. Dr England is currently the Senior Medical Director and VP of Medical Affairs at OneOme LLC, a med tech company located in Minneapolis, MN.
