The Patient

• A 20 year old female presented with major depressive disorder. The patient had a history of good grades in school but began failing classes and lost all motivation to study. She dropped out of school on medical leave. The patient had a partial response to escitalopram (Lexapro^®); however, motivation issues remained. While on escitalopram, she stated she “can’t imagine anything except sleeping.”
• Past relevant medical history: None.
• Family history: Mother has depression. The patient has two maternal aunts with depression and anxiety who “both responded well to Lexapro^®.”
• Substance use: None.
• Previous medication trials: None.
• Medication at the time of GeneSight^® testing: escitalopram (Lexapro^®) 10mg daily.
• The physician ordered GeneSight as a way to utilize pharmacogenomic information to help support the “next steps” in treatment.

GeneSight^® Psychotropic Results

The patient’s genetic results for each of the genes were identified as:

PHARMACOGENOMIC INSIGHT

• This patient had inherited one “short” allele for the serotonin transporter, which suggests a pharmacodynamically-driven poorer response to SSRIs than if she had inherited two “long” alleles.^5-6 In addition, escitalopram is partially metabolized by CYP2C19, for which the patient has reduced activity. The physician chose to switch to bupropion, an antidepressant that does not work through the serotonin system.
• The patient may have been expected to do well on escitalopram since several family members had responded to it in the past. Indeed, family history has historically been used as an indicator of patient response, but it is rapidly becoming an anachronism in the era of personalized medicine. Because children receive one copy of each gene from each parent, a child’s phenotype may be completely different from either parents’ phenotype.⁷ In this case, pharmacogenomic testing helped to explain the poor response to escitalopram and guided the clinician to a more appropriate medication without the need for multiple medication trials.

Pharmacogenomic-Informed Decision Making

• The healthcare provider noted that escitalopram was categorized into the yellow (“Use with Caution”) category, suggesting a moderate gene-drug interaction. The footnotes stated, “serum level may be too high, lower doses may be required” and “genotype may impact drug mechanism of action and result in reduced efficacy.”
• The healthcare provider also noted the bupropion was categorized into the green (“Use as Directed”) category, suggesting no known gene-drug interaction.
• After the review of patient profile results, the patient was tapered off escitalopram and put on to bupropion.

Conclusions

After being cross tapered to bupropion, the patient noted that she wakes up “ready to start the day and in a good mood.” She feels “really happy” and “back on track” with improvement in somnolence and motivation. She stated, “[I am] so glad we did the testing!”

1. Hall-Flavin DK, et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013 Oct;23(10):535-48. [PMID: 24018772].
2.  Hall-Flavin DK, et al. Using a pharmacogenomic algorithm to guide the treatment of depression. Transl Psychiatry. 2012 Oct 16;2:e172. [PMID: 23047243].
3. Winner JG, et al. A prospective, randomized double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med. 2013 Nov;16(89):219-27. [PMID: 24229738].
4. Winner JG, et al. Psychiatric pharmacogenomics predicts health resource utilization of outpatients with anxiety and depression. Transl Psychiatry. 2013 Mar 19;3:e242. [PMID: 23511609].
5. Porcelli, S., Fabbri, C., & Serretti, A. (2012). Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology, 22(4), 239–58. doi:10.1016/j.euroneuro.2011.10.003
6. Serretti, a, Kato, M., De Ronchi, D., & Kinoshita, T. (2007). Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Molecular Psychiatry, 12(3), 247–57. doi:10.1038/sj.mp.4001926
7. Mrazek, D. (2010). Psychiatric pharmacogenomics. New York: Oxford University Press.