UGT1A4*3 ultrarapid metabolizer genotype: A case report
Clinical Genetics and Therapeutics
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Primary Categories:
- Genomic Medicine
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Secondary Categories:
- Genomic Medicine
Introduction
With the various pharmaceutical options used in the field of psychiatry, there are unsurprisingly genotypic anomalies that react unexpectedly to medications. These variations can present as supratherapeutic toxicity or subtherapeutic levels. It is notable that up to 40% of patients will stop taking a medication after 90 days if there are side effects, affecting adherence and long-term patient goals. GeneSight psychotropic pharmacogenetics testing has become increasingly popular to pick up these anomalies and change medication dosage appropriately. Below we present a case that proves the utility of the system.
Case Presentation
A 54 year old female presented for involuntary psychiatric hospitalization due to worsening symptoms of schizoaffective disorder. She has a history of five previous psychiatric hospitalizations, and was most recently discharged to a group home stabilized on 20 mg olanzapine, 1 mg benztropine, and 300 mg lithium. Leading up to the current hospitalization, she was seen at an outpatient mental health clinic for unknown reasons where her olanzapine was switched to aripiprazole and then haloperidol. Stability could not be achieved, precipitating rehospitalization with recurrence of visual, auditory, and tactile hallucinations and delusions. At that facility, she was transitioned back to olanzapine and later olanzapine-samidorphan to control weight gain. She was then transferred to the current facility, at which time the patient was taking lithium 300 mg for mood stabilization and olanzapine-samidorphan 20/10 mg for control of psychotic symptoms.
Diagnostic Workup
Initially, her lithium dose was adjusted after serum level was found to be subtherapeutic. Despite this change, the patient continued to have worsening psychotic symptoms with new gastrointestinal upset including abdominal pain, nausea, and emesis. The psychiatrist continued to monitor serum levels and adjust medications over the coming weeks to optimize care. Serum olanzapine level was subsequently drawn on week 14 of admission and found to be therapeutic at 47 ng/mL. An additional 5 mg of olanzapine was added in addition to the patient’s nightly regimen on week 16; Nonetheless, the patient continued to have persistent psychotic symptoms with continuing gastrointestinal upset. The nutritionist, allergist, psychiatrist worked together to rule out extraneous causes of the symptomatology. Gastrointestinal symptoms were therefore narrowed to an adverse drug reaction or high emotional reactivity.
Efforts were then focused on monitoring serum olanzapine levels. On week 21, serum level was measured at 73 ng/mL. On week 22, serum level was drawn again and found to be 42 ng/mL. Week 25 revealed a supratherapeutic level at 83 ng/mL, despite no olanzapine dose changes occurring since the monitoring. Notably, the patient was medication compliant through this period. These inconsistencies prompted GeneSight testing to be ordered.
Treatment and Management
Results indicated heterozygosity of the UGT1A4 gene with the genotype UGT1A4*1/UGT1A4*3, which predicts an ultrarapid metabolizer phenotype for the drug olanzapine. Given these results, the additional 5 mg olanzapine was discontinued and the patient began a cross taper from olanzapine-samidorphan to aripiprazole. The patient showed subsequent improvement in both gastrointestinal upset and psychotic symptoms. Once fully stabilized, she will be transferred to a step down facility.
Conclusion
GeneSight psychotropic pharmacogenetic testing should be considered and used more frequently in cases of unexplained symptomatology or pathology refractory to treatment, especially if a patient is continually switching pharmaceuticals with little to no change in symptoms. This form of testing has gotten significantly more affordable and accessible since its inception.
It is important to note, the phenotypic expression does not always match the predicted genotype, but the ability to test genetic compatibility enables providers to select drugs that are most likely to be compatible, avoiding needless trial and error. This will allow for expedited stabilization and reintegration into the community.
With the various pharmaceutical options used in the field of psychiatry, there are unsurprisingly genotypic anomalies that react unexpectedly to medications. These variations can present as supratherapeutic toxicity or subtherapeutic levels. It is notable that up to 40% of patients will stop taking a medication after 90 days if there are side effects, affecting adherence and long-term patient goals. GeneSight psychotropic pharmacogenetics testing has become increasingly popular to pick up these anomalies and change medication dosage appropriately. Below we present a case that proves the utility of the system.
Case Presentation
A 54 year old female presented for involuntary psychiatric hospitalization due to worsening symptoms of schizoaffective disorder. She has a history of five previous psychiatric hospitalizations, and was most recently discharged to a group home stabilized on 20 mg olanzapine, 1 mg benztropine, and 300 mg lithium. Leading up to the current hospitalization, she was seen at an outpatient mental health clinic for unknown reasons where her olanzapine was switched to aripiprazole and then haloperidol. Stability could not be achieved, precipitating rehospitalization with recurrence of visual, auditory, and tactile hallucinations and delusions. At that facility, she was transitioned back to olanzapine and later olanzapine-samidorphan to control weight gain. She was then transferred to the current facility, at which time the patient was taking lithium 300 mg for mood stabilization and olanzapine-samidorphan 20/10 mg for control of psychotic symptoms.
Diagnostic Workup
Initially, her lithium dose was adjusted after serum level was found to be subtherapeutic. Despite this change, the patient continued to have worsening psychotic symptoms with new gastrointestinal upset including abdominal pain, nausea, and emesis. The psychiatrist continued to monitor serum levels and adjust medications over the coming weeks to optimize care. Serum olanzapine level was subsequently drawn on week 14 of admission and found to be therapeutic at 47 ng/mL. An additional 5 mg of olanzapine was added in addition to the patient’s nightly regimen on week 16; Nonetheless, the patient continued to have persistent psychotic symptoms with continuing gastrointestinal upset. The nutritionist, allergist, psychiatrist worked together to rule out extraneous causes of the symptomatology. Gastrointestinal symptoms were therefore narrowed to an adverse drug reaction or high emotional reactivity.
Efforts were then focused on monitoring serum olanzapine levels. On week 21, serum level was measured at 73 ng/mL. On week 22, serum level was drawn again and found to be 42 ng/mL. Week 25 revealed a supratherapeutic level at 83 ng/mL, despite no olanzapine dose changes occurring since the monitoring. Notably, the patient was medication compliant through this period. These inconsistencies prompted GeneSight testing to be ordered.
Treatment and Management
Results indicated heterozygosity of the UGT1A4 gene with the genotype UGT1A4*1/UGT1A4*3, which predicts an ultrarapid metabolizer phenotype for the drug olanzapine. Given these results, the additional 5 mg olanzapine was discontinued and the patient began a cross taper from olanzapine-samidorphan to aripiprazole. The patient showed subsequent improvement in both gastrointestinal upset and psychotic symptoms. Once fully stabilized, she will be transferred to a step down facility.
Conclusion
GeneSight psychotropic pharmacogenetic testing should be considered and used more frequently in cases of unexplained symptomatology or pathology refractory to treatment, especially if a patient is continually switching pharmaceuticals with little to no change in symptoms. This form of testing has gotten significantly more affordable and accessible since its inception.
It is important to note, the phenotypic expression does not always match the predicted genotype, but the ability to test genetic compatibility enables providers to select drugs that are most likely to be compatible, avoiding needless trial and error. This will allow for expedited stabilization and reintegration into the community.