Pharmacogenomics Guided Prescription Changes Improved Medication Effectiveness in Patients With Mental Health-Related Disability: A Retrospective Cohort Analyses.

Mental health problems are the leading cause of disability in Canadian workers. Medication ineffectiveness is hypothesized to increase the time to return-to-work in these workers. We assessed whether prescription changes based on pharmacogenomics profiling ( Report®) improved medication effectiveness in patients on mental health-related disability. In this retrospective cohort analyses, we assessed the impact of pharmacogenomic profiling on patient outcomes in 84 Canadian workers who were on a mental health-related disability between May 2018 and May 2019. All patients completed an informed consent form and a standard questionnaire including medical history, medications, disease symptoms, and medication side effects. Licensed pharmacists made recommendations for prescription changes in 83 patients. The main study outcome was medication effectiveness defined on a scale of 0 to 10 (0 being most effective and 10 being most ineffective) based on reported mood toward regular work tasks and medication side effects. We compared the medication effectiveness at baseline and at 3 months after the pharmacogenomics-based prescription changes. This retrospective cohort analyses included 46 patients who completed the follow-up questionnaires. Of them, 54% (n = 25) were females, 67% (n = 31) were Caucasians, and the mean age was 38 years (standard deviation [SD] = 11). The average baseline effectiveness score was 8.39 (SD =1.22). Following the prescription changes, the medication effectiveness scores significantly improved to an average of 2.30 (SD = 1.01) at 3 months of follow-up (effect size r = 0.62, p = <0.001). Pharmacogenomics could help in improving treatment outcomes in patients on mental health-related disability.

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control.

AIMS/HYPOTHESIS: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. METHODS: We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. RESULTS: The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10-21 and p = 9.6 × 10-31, respectively) and a 4.4-fold (p = 6.8 × 10-33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. CONCLUSIONS/INTERPRETATION: This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Impact of early use of long-acting injectable antipsychotics on psychotic relapses and hospitalizations in first-episode psychosis.

Early relapse is frequent in the first-episode psychosis (FEP), often because of poor adherence to medication. Previous studies have shown positive impacts of long-acting injectable antipsychotics (LAI-AP) on relapse rates, while others have discerned no differences. This study describes the impact of early LAI-AP utilization on relapse and rehospitalization rates in FEP. A three-year, longitudinal, prospective, naturalistic study of all admissions of psychosis patients for early intervention services was conducted. Four hundred sixteen patients were subdivided into four groups according to the route of antipsychotic administration. Patients who received LAI-AP as their first treatment modality were more likely to exhibit poor prognostic factors at baseline. However, their relapse rate over time was similar to those with good prognostic factors at baseline who only received oral antipsychotics (OAP). Patients who were initially prescribed OAP and eventually switched to LAI-AP were more likely to relapse and to be rehospitalized, even if they manifested better functioning at baseline than those started on LAI-AP. Patients with poor prognosis in the early stage of their disease seem to benefit from early prescription of LAI-AP which can reduce and delay relapses and rehospitalizations. Because they are often still at school or at work at the time of their first episode of psychosis, relapse prevention seems particularly relevant to avoid functional deterioration.

Long-acting antipsychotic medication as first-line treatment of first-episode psychosis with comorbid substance use disorder.

AIM: Substance use disorder (SUD) is highly prevalent among patients with first-episode psychosis (FEP) and associated with poor adherence and worst treatment outcomes. Although relapses are frequent in FEP, current literature on long-acting injectable antipsychotics (LAI-AP) use in FEP is scarce and studies often exclude patients with SUD. OBJECTIVES: To determine the impact of LAI-AP as first-line treatment on psychotic relapses or rehospitalizations in FEP patients with comorbid SUD (FEP-SUD). METHODS: This is a naturalistic, longitudinal, 3-year prospective and retrospective study on 237 FEP-SUD admitted in two EIS in Montreal, between 2005 and 2012. The patients were divided on the basis of first-line medication introduced, either oral antipsychotics (OAP, n = 206) or LAI-AP (n = 31). Baseline characteristics were compared using χ² test and analysis of variance, and Kaplan-Meier survival analysis was performed on relapse and rehospitalization. RESULTS: Compared to the OAP group, patients in the LAI-AP group presented worse prognostic factors (eg, history of homelessness). Despite this, the LAI-AP group presented a lower relapse rate (67.7% vs 76.7%), higher relapse-free survival time (694 vs 447 days, P = 0.008 in Kaplan-Meier analysis), and trends for reduced rehospitalization rates (48.4% vs 57.3%) and hospitalization-free survival time (813 vs 619 days, P = 0.065 Kaplan-Meier analysis). Of those receiving OAP as first-line, 41.3% were eventually switched to LAI-AP and displayed worst outcome in relapse and rehospitalization. CONCLUSION: LAI-AP should be strongly considered as first-line treatment of FEP-SUD patients since this pharmacological option reduces the risk of relapse and rehospitalization even in the individuals with poor prognostic factors.