The Utility of Pharmacogenetics Testing in Psychiatric Populations

The implementation of pharmacogenetic tests including multiple gene variants has shown promising potential as a decision-making tool for optimizing psychopharmacological treatment regimens and reducing treatment costs. However, the varying clinical validity of gene variants included in pharmacogenetic test batteries, and inconsistencies in their translation into medical recommendations between commercially available pharmacogenetic tests, complicates their rational implementation. Thus, there is a need for well-designed, reproducible studies documenting the clinical significance of the various genetic variants.

Pilot study of multi-gene pharmacogenetic testing for pain management in oncology palliative medicine

Aim: We evaluated the application and clinical impact of multi-gene pharmacogenetic testing in oncology palliative medicine. Patients & Methods: In a single-arm pilot trial, cancer patients with uncontrolled pain were assessed in a palliative medicine clinic at baseline and received pharmacogenetic testing. Results were used as applicable up to the final visit (day 30). Pain scores, opioid prescribing, and use of pharmacogenetic test results were collected. Results: In 75 patients, the median baseline pain score was 7/10. Of 54 evaluable at the final visit, 28 required opioid modifications and 19 had actionable genotypes, mostly CYP2D6. Pain improvement (≥2-point reduction) was higher than historical data (56 vs 30%; p < 0.001). There were no differences in pain improvement between those with and without actionable genotypes (61 vs 53%). Conclusion: Multi-gene testing identified actionable genotypes and may improve cancer pain.

A case of olanzapine-associated rhabdomyolysis

AimsTo describe the case of olanzapine-associated rhabdomyolysis in a 20-year-old patient with a suspected diagnosis of paranoid schizophrenia.MethodA 20-year-old male Caucasian patient was admitted to the Psychiatric Department with a one-month history of irrational behavior, talking to himself, persecutory delusions, and poor sleep. He was prescribed oral olanzapine at a dose of 10 mg per day. After two days of olanzapine monotherapy, the patient experienced muscle jerks in the legs. Four days after the initiation of olanzapine treatment, he complained about fatigue and weakness in the lower extremities along with myalgia. Physical examination revealed decreased muscle power with no extrapyramidal symptoms. Blood chemistry showed serum creatine kinase (CK) and serum lactate dehydrogenase (LDH) of 9,725 U/L and 843 U/L, respectively, on day four of the therapy. The Naranjo algorithm score of 6 suggested that olanzapine was the probable cause of rhabdomyolysis. A diagnosis of drug-induced rhabdomyolysis was established from the background of blood tests (increased serum CK and LDH levels), clinical presentation (fatigue and weakness in the lower extremities, muscle jerks, and myalgia), and Naranjo algorithm score of 6 for olanzapine. On suspicion of its contribution to rhabdomyolysis, olanzapine was immediately withdrawn. The patient was referred to the intensive care unit. To prevent acute renal failure, high-volume alkaline diuresis was initiated. After consulting a clinical pharmacologist, the patient's primary physician decided to perform a pharmacogenetic test to develop an individualized treatment regimen. Pharmacogenetic test results were interpreted using the PGX2 software (Meditsina LLC, Moscow, Russia). The test revealed that the patient was a homozygous mutant for CYP2D6*4, which corresponds to CYP2D6 PM phenotype. With this in mind, trifluoperazine was prescribed at a daily dose of 10 mg instead of olanzapine as recent data indicate that trifluoperazine is metabolized by CYP1A2 and UGT1A4 instead of CYP2D6. Subsequently, the patient recovered well and was discharged without any nephrological sequelae.ResultRecent research demonstrates that CYP2D6 is one of the most important isoenzymes implicated in drug metabolism because the CYP2D6 gene is highly polymorphic. Few reports on the association between olanzapine use and rhabdomyolysis have been published to date, and the present case report draws attention to pharmacogenetic testing which allowed the psychiatrist to prescribe another antipsychotic with no risk of rhabdomyolysis.ConclusionThe presented case demonstrates that pharmacogenetic-guided personalization of treatment may allow selecting the best medication and determining the right dosage, resulting in the reduced risk of adverse drug reactions and pharmacoresistance.

GENETIC MARKERS OF PHARMACORESISTANCE IN SCHIZOPHRENIA

The study of genetic markers of pharmacoresistance in schizophrenia, significant for the population of the Republic of Belarus, such as polymorphisms CYP2D6*4, CYP2C19*2, CYP2C19*17, CYPU2*F, С3435Т MDR1, TaqI ANKK1, d019G mRM, Val158Met СОМТ, Val66Met BDNF, C957T DRD2 was implemented. The possibilities of their use in predicting an adverse pharmacological response were described. Data on the use of genetic markers to determine the tactics of treating patients with schizophrenia were obtained; the sensitivity and specificity of the pharmacogenetic test for each marker were calculated. Specific genetic markers, such as polymorphisms CYP2D6*4, CYP2C19*2, CYP2C19*17, CYP1A2*F, C3435T MDR1, TaqI ANKK1, have been identified, which should be preferred for inclusion in diagnostic panels when predicting an adverse pharmacological response in the treatment of schizophrenia.

Using a biomarker acutely to identify babies at risk of serious adverse effects from antibiotics: where is the ‘Terrible Moral and Medical Dilemma’?

We thank Parker and Wright for engaging in this roundtable debate in such a spirited way. The ‘Pharmacogenetic [test] to Avoid Loss of Hearing’ (PALOH) Trial is the first time a genetic point of care test has been applied in the acute neonatal setting; therefore, it is not surprising that questions have been raised which require debate, discussion and clarification. Parker and Wright misattribute several assumptions to the roundtable authors, which we would like to clarify here. Since they raise wider questions about the PALOH trial itself, several of the roundtable discussants have made a joint response.

Are pharmacists from the province of Quebec ready to integrate pharmacogenetics into their practice

Aim: The pharmacists are identified as one of the best positioned health professionals to lead intercollaborative efforts in tailoring medication based on pharmacogenetic information. As pharmacotherapy specialists, they can take on a prominent role in ordering and interpreting pharmacogenetic test results and then guiding optimal drug selection and dose based on those results. Participants & methods: To assess the readiness of pharmacists and trainees in the province of Quebec to assume this role, we surveyed their knowledge in (pharmaco)genetics, their confidence in their ability to use pharmacogenetics and their attitude toward the integration of this tool in clinical practice. Results: A total of 99 pharmacists (community: 67.7%, hospital: 24.2% and other: 8.1%) and 36 students volunteered in a self-administered online survey. About 50% of the questions on the participants’ knowledge are answered correctly, with a stepwise increase of right answers with hours of education in (pharmaco)genetics (51.2, 63.8 and 76.7% for <5, 5–25 and >25 h respectively; p < 0.0001). While the majority of participants believe that pharmacogenetics will gain more room in their future practice (80.7%), the overall rate of confidence in their ability to use pharmacogenetics information is low (22%) and 90.3% desire more training. Conclusion: The limited experience of pharmacists in pharmacogenetics appears to be a barrier for its integration in clinical practice.