CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series

RATIONALE: In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.PATIENT CONCERNS: We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).DIAGNOSES: Psychiatric patients affected by Bipolar Disorder.INTERVENTIONS: We defined TFs as a difference at the Brief Psychiatric Rating Scale score \u394BPRS\u200a<\u200a25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain.OUTCOMES: At 3 months, a mean number of 2.75\u200a\ub1\u200a1.26 ADR and a mean \u394BPRS score of 16.07\u200a\ub1\u200a0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (\u394BPRS\u200a<\u200a32.10%), BD patients (n\u200a=\u200a4) showed TFs (\u394BPRS\u200a<\u200a25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3.LESSONS: Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD

The pharmacogenetic road to avoid adverse drug reactions and therapeutic failures in revolving door patients with psychiatric illnesses: focus on the CYP2D6 isoenzymes

Introduction: A periodical hospital readmission caused by therapeutic failures (TFs) and a worsening of clinical symptoms most often linked to adverse drug reactions (ADRs) are probably the major causes for the so-called revolving door condition in psychiatric illnesses. This review underlined the importance that pharmacogenetic data on cytochrome P450 (CYP), particularly CYP2D6 polymorphisms, may offer for the finger printing of the pharmacological treatment of psychiatric illnesses, given the relevance of this enzyme in metabolizing psychotropic drugs. Areas covered: We searched in the medical literature until July 2016 to review the role of functional variants in the CYP2D6 gene on observed ADRs and TFs in revolving door psychiatric patients. Expert commentary:CYP2D6 gene variants could in part explain the revolving door condition in patients attending a psychiatric setting. The preemptive known CYP genotypes associated to a reduced metabolizer status may help clinical decision-making to avoid concomitant treatments, increasing drug safety, so reducing therapeutic attempts, hospital admission, and the overall costs for the national health services. However, CYP2D6 gene is only a part of a complex mechanism in which genetic and non-genetic factors may take part. A possible role of the intrinsic variability of pharmacodynamics and imponderable environmental factors influencing the revolving door condition cannot be excluded

Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?

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Macroscopic Synovial Inflammation Correlates with Symptoms and Cartilage Lesions in Patients Undergoing Arthroscopic Partial Meniscectomy: A Clinical Study

Background: The aim of the study was to examine the relationship among patients' characteristics, intraoperative pathology and pre/post-operative symptoms in a cohort of patients undergoing arthroscopic partial meniscectomy for symptomatic meniscal tears. Methods: Clinical data were collected (age, sex, body mass index, time to surgery, trauma). Intraoperative cartilage pathology was assessed with Outerbridge score. Meniscal tears were graded with the ISAKOS classification. Synovial inflammation was scored using the Macro-score. Patient symptoms were assessed pre/post-operatively using the KOOS instrument. Results: In the series of 109 patients (median age 47 years), 50% of the meniscal tears were traumatic; 85% of patients showed mild to moderate synovitis; 52 (47.7%) patients had multiple cartilage defects and 31 (28.4%) exhibited a single focal chondral lesion. Outerbridge scores significantly correlated with patient age, BMI and synovial inflammation. There was a correlation between severity of chondral pathology and high-grade synovial hyperplasia. Pre-operative KOOS correlated with BMI, meniscal degenerative changes and symptom duration. Obesity, time to surgery, presence of high-grade synovial hyperplasia and high-grade cartilage lesions were independent predictors of worse post-operative pain and function. Conclusion: We demonstrated that pre-operative symptoms and post-operative outcomes correlate with synovitis severity and cartilage pathology, particularly in old and obese patients that underwent arthroscopic partial meniscectomy. Importantly, patients with a degenerative meniscal pattern and with longer time to surgery experienced more severe cartilage damage and, consequentially, pain and dysfunction. These findings are fundamental to identify patients suitable for earlier interventions

Pharmacogenetics in the clinical analysis laboratory: clinical practice, research, and drug development pipeline

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