Impact of sex on antidepressant discontinuation in groups of similar cytochrome P450 phenotypes.

Introduction: Although there are studies assessing reasons for antidepressant discontinuation, little is known about the impact of sex differences or cytochrome P450 phenotypes. Our objective is to assess discontinuation rates between males and females and whether CYP450 phenotype influences discontinuation. Methods: This is a retrospective review of patients previously enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment database with major depressive disorder. Patients were evaluated for antidepressants trialed between January 1, 2009, and September 30, 2019. Survival analyses with competing risks were used to analyze discontinuation reasons. A Kaplan-Meier estimation method was used to assess the time to discontinuation and discontinuation rates. Analyses were also completed to assess discontinuation between men and women by phenotypic groups. All tests were two-sided, and p-values ≤ .05 were considered statistically significant. Results: There were 620 antidepressant discontinuation events discovered from 1015 antidepressant trials included. Overall, the median time to discontinuation for males was 2.6 years and 1.9 years for females (hazard ratio [HR] 0.97 [95% confidence interval (CI): 0.80, 1.19], p = .77). The risk of discontinuation was not different between males and females in any of the phenotype groups, which was consistent in the multivariable analyses. Concomitant use of medications that inhibited or induced antidepressant metabolism increased the overall risk of discontinuation (HR 1.45, 95% CI [1.06, 1.99], p = .020) in a time-dependent analysis. Discussion: We did not detect a significant difference in risk of antidepressant discontinuation rates between males and females even when accounting for cytochrome P450 phenotype. Future studies should account for whether medications that inhibit or induce antidepressant metabolism may be a crucial factor in antidepressant discontinuation.

Pharmacists' role in supporting the return of over 10,000 preemptive pharmacogenomics results: The Mayo Clinic experience.

PURPOSE: To develop a pharmacist-driven, exploratory pharmacogenomics implementation model with the goal of creating a process for pharmacists to interpret pharmacogenomics results from RIGHT 10K Study samples and provide electronic consults to providers. SUMMARY: A train-the-trainer model program was initiated whereby pharmacogenomics pharmacists developed a documentation template and a quick reference guide as a standard guide to train other pharmacists. Pharmacists completed electronic consults (e-consults) reviewing pharmacogenomics results, with reference to drug-gene interactions, for patients with "semi-urgent" and "clinically actionable" results, defined as those indicating a potential for gene-drug interactions to cause major harm and those indicating a potential for an adverse drug reaction or reduced efficacy, respectively. Outcomes measured included the number of consults over time, number and role of pharmacists involved, average time to complete e-consults over time, and gene-drug pairs for semi-urgent consults per month. A total of 395 pharmacists were trained. The total number of e-consults completed was 2,843: 61 semi-urgent and 2,782 clinically actionable consults. The average time spent per consult was 24 minutes, and the average number of e-consults per pharmacist was 7. CYP2C19-clopidogrel was the most common gene-drug pair targeted in semi-urgent consults. CONCLUSION: Pharmacy leaders planning to implement similar pharmacogenomics programs can utilize this data to estimate hiring needs for future pharmacogenomics implementation, while also considering the potential additional cost of developing resources.

Pharmacogenomics testing in patients with liver transplant and potential impact on prospective management.

Aim: Pharmacogenomics (PGx) tests are performed on whole-blood or saliva specimens. In patients with a transplanted liver, PGx results may be discordant with hepatic drug metabolizing enzyme activity. We evaluate the incidence and impact of PGx testing in liver transplant recipients, detail potential errors and describe clinical decision support (CDS) solution implemented. Materials & methods: A retrospective cohort study of liver transplant recipients at Mayo Clinic who underwent PGx testing between 1 January 1996 and 7 October 2019 were characterized. Impact of a CDS solution was evaluated. Results: There were 129 PGx tests in 117 patients. PGx testing incidence increased before (per year incidence rate ratio = 1.45, 95% CI: 1.20-1.74, p < 0.001) and after transplant (incidence rate ratio = 1.48, 95% CI: 1.27-1.72, p < 0.001). Three erroneous PGx tests were avoided 6 months following CDS implementation. Conclusion: Incidence of PGx testing in liver transplant recipients is increasing, leading to erroneous therapeutic decisions. CDS interventions and education are needed to prevent errors.

Duration of therapy with acetylcholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease as reported in the literature.

OBJECTIVE: To review the literature regarding the treatment duration of acetylcholinesterase inhibitor (AChEI) therapy for mild-to-moderate Alzheimer's disease (AD) patients. DATA SOURCES: A literature search was performed using MEDLINE/PubMed, Embase, International Pharmaceutical Abstracts, and Clinical Key (all through May 31, 2013) with the search terms Alzheimer's disease, cholinesterase inhibitors, dementia, treatment and duration, with limits to human, clinical, and observational trials, and English studies; no limits were placed on publication dates. STUDY SELECTION AND DATA EXTRACTION: Based on the study selection, 40 studies were identified. The criteria for studies reviewed focused on the duration of AChEIs in patients with mild or moderate AD for a minimum of one year. DATA SYNTHESIS: Based on the selection criteria, five studies were reviewed. These studies evaluated the cognitive efficacy of AChEI after "long-term" (1.5 years) treatment in the clinical trial with follow-up noted in the observational studies of a maximum of "greater than 3 years" (up to 7 years). Cognitive decline was measured by changes in Mini-Mental State Exam scores or Alzheimer's Disease Assessment Scale scores. There were no studies identified that suggested an optimal duration of AChEI therapy for AD patients. CONCLUSION: Based on the trials reviewed, the duration for AChEI use is very patient-specific; therefore, risk versus benefit of therapy needs to be evaluated regularly in AD patients. The maximum mean duration of follow-up in the clinical study analyzed here was only 1.5 years and observational studies with follow-up "greater than 3 years." Further long-term research is needed.