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Optimistic About Life: 59 year old with Major Depressive Disorder

Optimistic About Life: 59 year old with Major Depressive Disorder

A GeneSight® Psychotropic Case Study

Background

Behavioral health drug selection and dosing is a trial and error process that often leads to delayed response time, frustration and increased medical costs. There is a high degree of variability in response to behavioral health medications, some of which is due to individual genetics. Assurex Health utilizes its GeneSight pharmacogenomic technology to understand how unique inherited traits might influence a patient’s response to medication. GeneSight Psychotropic is a pharmacogenomic test developed to help clinicians select medications commonly prescribed to treat behavioral health conditions. There have been multiple studies published in peer reviewed journals addressing the clinical utility of GeneSight Psychotropic.1-4

The Patient

  • 59 year old male who presents with symptoms of fatigue, depressed mood, and lack of motivation
  • Primary diagnosis: Major depressive disorder, recurrent, severe, without psychotic features
  • Past medical history: Patient suffers from chronic pain; history of acute and chronic pancreatitis s/p Whipple (pancreatoduodenectomy) procedure
  • Family history: Patient’s father is a recovered alcoholic; mother suffers from alcoholism and anxiety disorder; sister is an alcoholic; sister has unspecified personality disorder and is estranged from family; son and daughter both suffer from alcohol and drug abuse
  • Social history: No known problems with alcohol or illicit drugs
  • Previous psychiatric medications include: escitalopram (Lexapro®), venlafaxine (Effexor®), amphetamine/dextroamphetamine salt (Adderall®), and amitryptiline (Elavil®)
  • Medications at the time of GeneSight® testing: duloxetine (Cymbalta®) 60 mg daily
  • The physician ordered GeneSight as a way to utilize genomic information to support her “next step” for this patient’s treatment.

GeneSight® Psychotropic Results

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

CYP2D6 Ultrarapid Metabolizer *2A/*2A
CYP2C19 Extensive Metabolizer *1/*1
CYP2C9 Poor Metabolizer *2/*3
CYP1A2 Extensive Metabolizer -163C>A – C/A, 5347C>T – C/T
SLC6A4 Moderate Activity L/5
HTR2A Reduced Activity G/G

PHARMACOGENOMIC INSIGHT

The patient was not improving on typical doses of duloxetine.  The physician noted that this patient is an ultrarapid metabolizer for CYP2D6, which is involved in the metabolism of duloxetine in the liver.  Additionally, this patient has had a Whipple (pancreatoduodenectomy) procedure which likely decreased the amount of medication absorbed through his stomach and small intestine.  This combination of poor absorption in the gut and increased elimination through CYP2D6 in the liver could lead to a decreased ability to achieve appropriate serum levels.  With this additional information, the physician made the clinical decision to increase the dose of duloxetine in an effort to improve the chance for efficacy.

Pharmacogenomic-Informed Decision Making

  • The physician notes that duloxetine is found in the red (“use with increased caution and with more frequent monitoring”) category for this patient.  Duloxetine is noted to have the footnote, “serum level may be too low, higher doses may be required.”
  • After review of the profile results, the patient was increased to duloxetine 180 mg daily.

MEDICATIONS AT TESTING CHANGE IN MEDICATIONS
duloxetine (Cymbalta®) 60 mg daily duloxetine increased to 180 mg daily

Conclusions

The physician reports, “Patient has said more than once that he has not felt so good in years … [He] is now able to set and complete tasks for himself.  He is more optimistic about his life and his value as a person.  Additionally, he has been able to taper back significantly on pain medications, which further improved his stamina and mood. He also reports now being engaged in an exercise routine.

  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].
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