Role of Pharmacogenomics in Comprehensive Medication Management: Considerations for Employers.

Rising prescription costs, poor medication adherence, and safety issues pose persistent challenges to employer-sponsored health care plans and their beneficiaries. Comprehensive medication management (CMM), a patient-centered approach to medication optimization, enriched by pharmacogenomics (PGx), has been shown to improve the efficacy and safety of pharmaceutical regimens. This has contributed to improved health care outcomes, reduced costs of treatments, better adherence, shorter durations of treatment, and fewer adverse effects from drug therapy. Despite compelling clinical and economic evidence to justify the application of CMM guided by PGx, implementation in clinical settings remains sparse; notable barriers include limited physician adoption and health insurance coverage. Ultimately, these challenges may be overcome through comprehensive programs that include clinical decision support systems and education through employer-sponsored population health management channels to the benefit of the employees, employers, health care providers, and health care systems. This article discusses benefits, considerations, and barriers of scalable PGx-enriched CMM programs in the context of self-insured employers.

Early Insights From a Pharmacogenomic-Enriched Comprehensive Medication Management Program Implementation in an Adult Employee Population.

OBJECTIVES: The aims of the study are to assess adoption of a pharmacogenomic-enriched comprehensive medication management program in a self-insured employer setting and to better understand medication risks that affect employees. METHODS: Employees were identified to be at high risk of medication mismanagement and were subsequently provided with a program and process to improve their health. DNA testing, a clinical decision support system, and pharmacists were used to identify medication safety and effectiveness issues and to recommend appropriate changes. RESULTS: A total of 10.6% of the invited employees enrolled in the program. Actionable recommendations were suggested by pharmacists for 85.8% of employees who completed the program, averaging 5.2 recommendations per person. CONCLUSIONS: Implementation of a PGx + CMM program in a self-insured employer setting is feasible, detects risks in prescription regimens, and offers opportunities to improve medication management and reduce the burden of healthcare expenses.

Changes in ganglioside antibody positivity rates during the COVID-19 pandemic.

Reports suggested an association between SARS-CoV-2 infection and GBS, but subsequent studies produced conflicting results regarding the incidence of GBS during the pandemic. This study assessed positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at a national laboratory. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b and 24% for GM-1, while unchanged for GD1a and GD1b. These findings suggest heterogeneity with positivity rates of GBS-associated ganglioside antibodies during the COVID-19 pandemic. Mitigation strategies during the pandemic may have reduced the frequency of certain forms of GBS.

Economic Utility: Combinatorial Pharmacogenomics and Medication Cost Savings for Mental Health Care in a Primary Care Setting.

PURPOSE: This study was an analysis based on a previously completed prospective study investigating medication costs of patients with mental illness guided by using the GeneSight proprietary combinatorial pharmacogenomic (PGx) test. The primary objective of this study was to determine potential cost savings of combinatorial PGx testing over the course of 1 year in patients with mental illness treated by primary care providers (PCPs) and psychiatrists who had switched or added a new psychiatric medication after patients failed to respond to monotherapy. The current evaluation details cost savings of treatment decisions congruent and incongruent with the combinatorial PGx test recommendations specific to PCPs and psychiatrists. METHODS: This study was a subanalysis of a 1-year, prospective trial comparing medication costs of 2168 patients undergoing GeneSight testing. Pharmacy claims were provided by a pharmacy benefits manager, comparing medication costs 6 months before combinatorial PGx testing and followed up for 1 year after the testing. This analysis compared congruence and cost savings per patient based on the type of health care provider administering care. FINDINGS: Using data from a large pharmacy benefits manager, we found that PCPs treat the majority of mental health patients receiving psychotropic medication prescriptions, including treatment-resistant patients. PCPs congruent with combinatorial PGx testing provided the most medication cost savings for payers and patients at $3988 per member per year (P < 0.001). IMPLICATIONS: Health care providers treating patients with mental illness can significantly reduce medication costs by following the combinatorial PGx report recommendations. PCPs, who treat the majority of patients with mental illness, reported a significant reduction in medication costs for both central nervous system and non-central nervous system drugs.

Use of combinatorial pharmacogenomic testing in two cases from community psychiatry.

This report describes two cases in which pharmacogenomic testing was utilized to guide medication selection for difficult to treat patients. The first patient is a 29-year old male with bipolar disorder who had severe akathisia due to his long acting injectable antipsychotic. The second patient is a 59-year old female with major depressive disorder who was not responding to her medication. In both cases, a proprietary combinatorial pharmacogenomic test was used to inform medication changes and improve patient outcomes. The first patient was switched to a long acting injectable that was not affected by his genetic profile and his adverse effects abated. The second patient had her medications discontinued due to the results of the genetic testing and more intense psychotherapy initiated. While pharmacogenomic testing may be helpful in cases such as these presented here, it should never serve as a proxy for a comprehensive biopsychosocial approach. The pharmacogenomic information may be selectively added to this comprehensive approach to support medication treatment.

Pharmacist self-reported antidepressant medication counseling.

OBJECTIVES: To identify the extent of pharmacists' self-reported antidepressant counseling (SRAC) and to identify factors that may affect pharmacists' decisions to provide antidepressant counseling. DESIGN: Cross-sectional study. SETTING: Alabama community pharmacies in 2011. PARTICIPANTS: Full-time pharmacists from 600 community pharmacies. INTERVENTION: Self-administered survey; three mail contacts with alternate electronic surveys were used. MAIN OUTCOME MEASURES: Pharmacists' SRAC behavior and its relationship with pharmacists' illness perceptions of depression, self-efficacy, and organizational and environmental influences. RESULTS: 600 surveys were sent; 22 were undeliverable, 1 was partially completed (<80% questions answered), and 118 were completed (20.6% overall response rate). Pharmacists reported low rates of involvement in antidepressant counseling; 61% reported assessing patient knowledge and understanding of depression, and 36% discussed options for managing adverse effects with no more than a few patients. More than one-quarter (28.6%) never asked patients whether they had barriers to taking antidepressants. Pharmacists' perceptions regarding consequences, control/cure, and the episodic nature of depression, as well as their self-efficacy, had significant relationships ( P < 0.05) with pharmacists' involvement in antidepressant counseling. CONCLUSION: Low rates of pharmacists' involvement in antidepressant counseling were reported. Pharmacists must become more involved in counseling patients about their antidepressant medications and overcoming barriers preventing greater involvement.

Factors associated with influenza vaccination decisions among patients with mental illness.

OBJECTIVE: To determine influenza (flu) vaccination status among the mentally ill population and identify factors associated with vaccination status. METHOD: A non-interventional, cross-sectional study was conducted. A self-administered survey to investigate the vaccination status and perceptions related to flu vaccine was administered between October 2011-January 2012 in an outpatient psychiatry clinic that served the indigent, severely mentally ill population of Alabama. All statistical analyses were based upon a significance level of 0.05. RESULTS: Of the 736 patients invited, 302 participated (41%). Only 28.4% were vaccinated in 2010-2011 and 24.2% had been vaccinated at the time of the survey for 2011-2012. Respondents who had private health insurance, received a recommendation from healthcare providers, and who perceived a greater degree of vaccine effectiveness were more likely to obtain flu vaccination while respondents who had education beyond high school and were more in agreement that they can get the flu from the vaccine were less likely to obtain flu vaccination. All of the above factors accounted for 26.7% of vaccination decisions. CONCLUSIONS: The flu vaccination rate among this study's population was lower than the general population. Interventions targeting the above factors should help increase vaccination rates among the mentally ill population.

Prazosin for the treatment of nightmares related to posttraumatic stress disorder: a review of the literature.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder with symptoms that include insomnia due to hyperarousal and recurring nightmares. These symptoms are believed to be due to a conditioned response that is regulated by norepinephrine. Prazosin, an α(1) antagonist, can decrease levels of norepinephrine in the central nervous system, thereby reducing nightmares related to PTSD. DATA SOURCES: A literature search was conducted for all studies evaluating the effectiveness of prazosin as therapy for nightmare symptoms of PTSD. MEDLINE was utilized to identify all English-language studies published between 1966 and March 2011. Keywords searched included prazosin, PTSD, and nightmares. RESULTS: Eleven studies were identified, including 4 open-label trials, 4 retrospective chart reviews, and 3 placebo-controlled trials. Prazosin demonstrated favorable clinical efficacy and was found to be safe for relieving PTSD-associated nightmares. CONCLUSIONS: Current data indicate that prazosin is an effective agent for the treatment of nightmares associated with PTSD. However, the data are limited by small study sizes, lack of diversified investigators, and lack of regional diversity.

Adjunctive use of atypical antipsychotics for treatment-resistant generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a common, chronic mental illness that has a significant burden on the patient's quality of life. Treatment for GAD routinely consists of monotherapy with a proven anxiolytic such as an antidepressant or benzodiazepine, but many patients do not respond fully to these drugs, and additional treatment may be needed. Therefore, we reviewed the safety and efficacy of atypical antipsychotics as adjunct therapy to standard GAD pharmacotherapy in patients deemed treatment resistant. We performed a literature search of the MEDLINE database for English-language articles published from January 1966-May 2009. Identified articles were evaluated, and only open-label trials and randomized controlled trials (RCTs) were included in the review. Relevant references from the articles were also evaluated. Only a few reports of large-scale RCTs that assessed an atypical antipsychotic for treatment-resistant GAD have been published. Articles were found for five of the eight currently available atypical antipsychotics, but not for asenapine, clozapine, and paliperidone. Several open-label trials and smaller RCTs support the need for further evaluation of aripiprazole and quetiapine for treatment-refractory GAD, although one quetiapine trial demonstrated negative results. There is disparate data for risperidone, with one open-label trial and one small RCT showing positive results and one large RCT showing negative results. One open-label trial of ziprasidone and one RCT of olanzapine both showed beneficial effects of the drugs. Adverse effects were specific to each agent, with weight gain being the most common, but many studies did not monitor systematically for lipid level, weight, or glucose level changes. Although data suggest efficacy regarding the use of atypical antipsychotics for augmentation of treatment-refractory GAD, more rigorous studies (large, double-blind, placebo-controlled trials) on the safety and efficacy of these agents are needed in order to recommend their use in patients with GAD.

Serotonergic antidepressants and linezolid: a retrospective chart review and presentation of cases.

OBJECTIVE: To report the results from a retrospective chart review looking at the combination of linezolid and serotonergic antidepressants and to report two cases of serotonin syndrome which were identified at our hospital. CASE SUMMARY: During the retrospective chart review one case of serotonin syndrome was identified. A 65-year-old female was receiving escitalopram for the treatment of depression prior to admission. Linezolid therapy was initiated on admission and two days later the patient had a tonic-clonic seizure. Escitalopram was discontinued and the patient did not have any further seizure activity. In a second case, a 37-year-old male was receiving citalopram during hospitalization and was started on concomitant linezolid. The patient had myoclonus and was observed to be tremulous throughout therapy with linezolid. Ten days after discontinuation of linezolid the patient continued to have symptoms until the withdrawal of citalopram. The Naranjo probability scale scores the first case as possibly related and the second case as probably related to the combination. DISCUSSION: It has been well documented in the literature that the combination of linezolid and serotonergic antidepressants may cause serotonin syndrome. In this retrospective chart review only one patient of 53 (1.8%) had symptoms highly suggestive of serotonin syndrome. A second patient continued to have symptoms of serotonin syndrome even after withdrawal of linezolid. CONCLUSIONS: This retrospective review and subsequent case reports confirm the rare, but serious, potential of serotonin syndrome associated with the combination of linezolid and serotonergic antidepressants.