PATIENT STORIES

We ask selected patients with remarkable clinical outcomes for their permission to publish their case histories in medical journals for research and teaching purposes. The 4 histories below are drawn from the clinical experiences of 4 real patients, who greatly benefited from personalized medicine. We thank them for allowing us to publish their cases, and we hope you will find these real histories both informational and inspirational.

  • Selection of Best Psychiatric Medicines: A Drug's Metabolic Requirements Should Match Your Innate Function
    Publication in Journal of the American Academy of Nurse Practitioners, 2011

A 40-year-old female of Irish American heritage was being followed after a 4-day psychiatric hospitalization for suicidal ideation and intent precipitated by her father's failing health and the anniversary of her mother's death. The patient's depression developed shortly after the death of her mother, 10 years ago. She subsequently sought treatment by her gynecologist and primary care physician for profound depression including sadness, lack of desire and self-esteem, insomnia, fatigue, decreased appetite, and difficulty with concentration. Drug therapy throughout the 10-year period included, individually or in combination, 5 antidepressants and a stimulant. When the patient went for outpatient assessment after hospital discharge to her psychiatric nurse practitioner, primary mental symptoms were clinically indistinguishable from potential drug side effects or adverse interactions. Functional deficits in drug metabolism were considered, and she was referred for DNA typing of CYP2C9, CYP2C19 and CYP2D6 genes. The patient had deficient functional status for CYP2C9 enzyme, functional for CYP2C19, and null for CYP2D6. Bupropion was tapered then and discontinued since it depends on metabolism by both CYP2C9 and CYP2D6 enzymes. She was placed on desvenlafaxine (Pristiq®) and alprazolam (Xanax®), neither of which is metabolized by the CYP enzymes assessed by DNA typing. Lanzoprazole (Prevacid®), a drug metabolized by CYP2C19, was continued as it was effective for her gastric acid-reflux. A significant subset of her symptoms gradually disappeared over a 3-month period by avoiding medications metabolized by CYP2D6 and CYP2C9 enzymes. The patient experienced then a significant improvement in mood, energy and concentration, and denies suicidal ideation.

  • Clopidogrel (Plavix®) and Heart Disease: Your Benefit Depends on Drug Metabolismn
    Publication in Connecticut Medicine, 2012

A 74-year-old man with a 22-year history of heart disease had required repeated interventions including coronary artery bypass grafting and experienced multiple failed attempts at balloon angioplasty. He underwent heart bypass in 1988 but had his symptoms return and needed stent implantation in 2002. Antiplatelet therapy with clopidogrel (Plavix®) at a dosage of 75 mg/day to supplement aspirin was started. The patient was taking his medications and was not being prescribed any gastric reflux drugs. Despite the clopidogrel therapy, the patient continued to experience chest pain over the next eight years. He underwent multiple subsequent cardiac catheterization interventions for obstruction of his coronary arteries and underwent placement of multiple stents. Due to persistent symptoms requiring interventions, the clopidogrel dose was increased to 150 mg per day. During high dose clopidogrel therapy, platelet function testing revealed non-therapeutic high residual platelet reactivity, confirming the presence of clopidogrel resistance. At this point, the patient was referred for CYP2C19 DNA typing for the possible presence of null gene alleles. Genotyping revealed the patient to have two copies of the *2 null allele. The *2/*2 designation indicates null metabolizer status, which indicates no capacity for activation of clopidogrel to its active form. A medication switch to prasugrel, which does not rely on activation by the CYP2C19 enzyme, resulted in decreased platelet reactivity (86% platelet inhibition). The patient has been free of cardiovascular events and chest pain since initiating prasugrel in May 2010.

  • Psychiatric Drugs and Side Effects: Critical Importance of Knowing Your Drug Metabolism Capacity
    Publication in Connecticut Medicine, 2007

A 54-year-old woman had problems with severe anxiety, multiple body complaints, side effects and adverse reactions to 18 psychiatric medications prescribed to her over the course of 6 years. She had stopped working as a marketing consultant, and had withdrawn from many of her usual activities and interests. Her difficulties had developed after the improper installation of a home heating system that allowed volatile fuels and products of combustion into the home. Since then she had extensively sought medical attention and treatment for a burning, metallic taste, dry mouth, nausea, vomiting, diarrhea, excessive sweating, weight gain, insomnia, muscle twitching, a "crawling feeling" beneath her skin, and mental "fogginess." During several interviews she was noted to be a pleasant, articulate and intelligent woman. Multiple deficits in drug metabolizing capacity were detected by DNA typing of the CYP2D6, CYP2C9, and CYP2C19 genes drug metabolism enzymes. The patient was null function for CYP2D6 enzyme and deficient for CYP2C9 and CYP2C19. This functional status was confirmed by DNA typing of her immediate family: parents, brother and children. Her brother had a similarly low drug metabolism capacity. The patient improved clinically when the psychiatric medications were discontinued, suggesting that many of her symptoms were drug-induced. After the drug washout she was prescribed clonazepam a drug not requiring metabolism by the enzymes, and she markedly recovered. DNA typing for multi-gene CYP deficiencies is diagnostically useful in individuals with histories of multiple side effects, which could be avoided by DNA-guided individualized prescription.

  • Warfarin Dosing and Bleeding: Benchmarking Drug Metabolism Capacity to Achieve Safe Blood Thinning Publication in Puerto Rico Health Sciences Journal, 2010

A 45-year-old Puerto Rican woman was admitted to the Emergency Department twice within one month with chest pain. She was diagnosed with congestive heart failure, which was stabilized both times. At her second release, warfarin (Coumadin®) therapy was initiated at 5 mg/day to prevent thrombus formation and was lowered to 3.75 mg/day at day 7 by her primary physician. International Normalized Ratio (INR) test results in the follow-up period at 1, 7, and 10 days after initiation of warfarin therapy were 4.5, 6.5, and 7.3, respectively, which are far above the therapeutic range 2-3, and prone to cause bleeding. Achieving the target INR required altogether 43 days after lowering the warfarin dose to 1.5 mg/day by empirical follow-up ("trial and error"). DNA-typing specific for the CYP2C9 and VKORC1 genes, revealed the presence of combinatorial CYP2C9 (*2/*3) and VKORC1 (-1639 G/A) genotypes in this patient. Entering the patient's demographic and genotype status data into algorithms available in the biomedical literature and databases to predict effective warfarin dose yielded predicted doses which ranged from 1.5 to 1.8 mg/day, which coincided with the patient's actual effective warfarin dose. The rapid rise in INR observed upon the initiation of warfarin therapy and the final effective warfarin dose of 1.5 mg/day, are attributable to the presence of 2 deficient function in the CYP2C9 enzyme, which together significantly reduce warfarin metabolism. CYP2C9 and VKORC1 genotyping can therefore inform the clinician of the predicted effective warfarin dose and prevent the haphazard risks of monitoring INR solely.