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:

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.

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.

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