Case A – Antipsychotic adverse reaction
Patient A has schizophrenia. Their treatment included a combination of ziprasidone, olanzapine, trazodone and benztropine. The patient experienced dizziness and sedation, so they were tapered off ziprasidone and olanzapine, and transitioned to quetiapine. Trazodone was discontinued. The patient then experienced excessive sweating, tachycardia and neck pain, gained considerable weight and had hallucinations. Five months later, quetiapine was tapered and discontinued, with ziprasidone re-introduced into their treatment, due to the excessive weight gain. Although the patient lost the excessive weight they had gained, they then developed muscle stiffness, cogwheeling, tremors and night sweats. When benztropine was added they experienced blurry vision. After an additional five months, the patient was switched from ziprasidone to aripiprazole. Over the course of 8 months, patient A gradually experienced more weight gain and sedation, and developed difficulty with their gait, stiffness, cogwheeling and dyskinetic ocular movements. A pharmacogenomics test later proved the patient had a CYP2D6 *1/*41, which has a predicted phenotype of IM and CYP2C19 *1/*2 with a predicted phenotype of IM as well.
Case B – Pain Management
Patient B is a woman who gave birth by caesarian section. Her physician prescribed codeine for post-caesarian pain. She took the standard prescribed dose, but she experienced nausea and dizziness while she was taking codeine. She also noticed that her breastfed infant was lethargic and feeding poorly. When the patient mentioned these symptoms to her physician, they recommended that she discontinue codeine use. Within a few days, both the patients and her infants symptoms were no longer present. It is assumed that if the patient had undergone a pharmacogenomic test, it would have revealed she may have had a duplication of the gene CYP2D6, placing her in the Ultra-rapid metabolizer (UM) category, explaining her reactions to codeine use.
Case C – FDA Warning on Codeine Overdose for Infants
On February 20, 2013, the FDA released a statement addressing a serious concern regarding the connection between children who are known as CYP2D6 UM, and fatal reactions to codeine following tonsillectomy and/or adenoidectomy (surgery to remove the tonsils and/or adenoids). They released their strongest Boxed Warning to elucidate the dangers of CYP2D6 UMs consuming codeine. Codeine is converted to morphine by CYP2D6, and those who have UM phenotypes are in danger of producing large amounts of morphine due to the increased function of the gene. The morphine can elevate to life-threatening or fatal amounts, as became evident with the death of three children in August 2012.