Protocol for the development of a consensus practice guideline To address clinical and regulatory barriers to buprenorphine dispensing in community pharmacy.

BACKGROUND: Less than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies. METHODS: The guideline development process will proceed in three phases, following a technique closely aligned with the Institute of Medicine's guidance on guideline development. The first phase will involve conducting qualitative interviews with pharmacists in three states to identify their beliefs toward buprenorphine dispensing. As limitations on buprenorphine supply are related to constraints at all levels of the drug supply and regulatory system, the second phase, we will recruit representatives from regulatory agencies, pharmacy organizations, the Drug Enforcement Administration, pharmaceutical wholesalers as well as addiction medicine physicians and psychiatric pharmacists to develop consensus recommendations through a modified Delphi design. This will be followed by a public comment period and external expert review of the recommendations led by the National Association of Boards of Pharmacy. Finally, in the third phase, a national, mixed media dissemination campaign will be led by the National Community Pharmacists Association (NCPA) to convey recommendations to practicing pharmacists. DISCUSSION: The guideline development process aims to incorporate the perspectives of multiple stakeholders and emphasize the importance of addressing the regulatory and pharmacy-specific aspects of care in addition to clinical evidence and guidance. The development of this guideline will provide targeted, multidisciplinary guidance for pharmacists, improving access to safe and effective opioid use disorder treatment in the community setting. PREREGISTRATION: This protocol was registered with the Open Science Framework in March of 2023. Registration may be found at: https://doi.org/10.17605/OSF.IO/6S9DY .

Adverse childhood experiences among California student pharmacists.

Introduction: Adverse childhood experiences (ACEs) are associated with higher mental and physical illness and substance use disorders in adulthood. However, little is known about the prevalence of ACEs among student pharmacists and the factors associated with exposure. Our objective was to determine the prevalence of ACEs, resilience, and maladaptive coping strategies among student pharmacists in California. Methods: Student pharmacists from 14 California pharmacy schools completed a 24-item online survey in 2020. This survey instrument comprised the ACEs questionnaire and collected data on the students' demographic characteristics, coping strategies, and resilience. Results: Most respondents were Asian/Pacific Islander (n = 186, 61.0%), female (n = 216, 70.8%), and aged between 25 and 31 years (n = 154, 50.7%). Many (n = 137, 44.9%) students had more than 1 ACE exposure; 66 students (21.6%) had more than 3 ACEs. Many students indicated that they were diagnosed or suspected to be diagnosed with a mental health condition (n = 105, 34.4%) and agreed/strongly agreed that they struggled to manage the workload of pharmacy school (n = 119, 39.9%). Respondents with higher ACE scores (> 3) were more likely to report struggling with managing the workload of pharmacy school, have or suspect having a mental health condition, drink alcohol in the last 12 months, and/or have multiple sexual partners than students with lower ACE scores. Discussion: More than 1 in 5 student pharmacists in this study were exposed to more than 3 ACEs. The student pharmacists' ACE exposure was associated with higher likelihood of mental health conditions and high-risk health behaviors. Further studies are needed to investigate this topic among student pharmacists.

Inappropriate quetiapine use at a large academic medical center: frequency of misuse and associated costs of adverse effects.

Background: Quetiapine is an antipsychotic with dose-related receptor affinity, which is commonly prescribed by specialties outside of psychiatry. Quetiapine can have adverse effects including weight gain, hyperglycemia, and falls. Therefore, quetiapine is a good focus medication to assess the need for an antipsychotic stewardship protocol. Objective: To assess the need for an antipsychotic stewardship protocol at a large, urban academic medical center by evaluating quetiapine usage. Design: A retrospective review of quetiapine dispensing history for all strengths (immediate release: 25, 50, 100, 200, 300 mg; extended release: 50, 150, 200, 300 mg) over 1 year (1 December 2021 to 30 November 2022) in patients aged 18 and older was conducted at a large, urban academic medical center. Methods: An antipsychotic protocol for safe and effective quetiapine use was developed utilizing its package insert, clinical guidelines, and primary peer-reviewed literature. Once identified by prescription fill, a retrospective chart review was completed for quetiapine indication, dose, and frequency. Each prescription was reviewed for appropriateness using the antipsychotic stewardship protocol. Results: Out of 521 quetiapine prescriptions for 181 unique patients, 67% of scripts were inappropriate. The costs associated with this inappropriate use were extrapolated to be over $350,000 per year when accounting for long-term harms associated with the development of type 2 diabetes mellitus and falls in older adults. Conclusion: Promoting the safe and effective use of antipsychotics through developing and implementing an antipsychotic stewardship protocol may reduce patient harm and associated costs from inappropriate use.

Inappropriate quetiapine use at a large academic medical center Psychotropic stewardship aims to improve patient outcomes and minimize side effects associated with psychotropic use ­ including antipsychotics. Studies have investigated psychotropic stewardship in elderly patients but have not reviewed its utility in the general adult population. Quetiapine is an antipsychotic with dose-related receptor affinity, meaning that at different doses of the medication, it acts on different receptors and exerts different clinical effects as a sedative, antidepressant, or antipsychotic. Quetiapine is commonly prescribed across medical specialties and can have significant adverse effects, including weight gain, hyperglycemia, and falls. Therefore, quetiapine is a suitable focus medication to assess the need for an antipsychotic stewardship protocol. We developed a protocol for safe and effective quetiapine use utilizing its package insert, clinical guidelines, and primary peer-reviewed literature. We reviewed the dispensing history of quetiapine over one year at two pharmacies at a large, urban academic medical center. Once identified by prescription fill, we completed a retrospective chart review for quetiapine indication, dose, and frequency. We reviewed each prescription for appropriateness using our antipsychotic stewardship protocol. Of 521 quetiapine prescriptions for 181 unique patients filled over one year, 67% of scripts were inappropriate. We extrapolated the costs associated with this inappropriate use to be over $350,000 per year when accounting for long-term harms associated with quetiapine use, including the development of type 2 diabetes mellitus and falls in older adults. Our findings illustrate that promoting the safe and effective use of antipsychotics through developing and implementing an antipsychotic stewardship protocol may reduce patient harm and associated costs from inappropriate use. Psychiatric pharmacists are well-positioned to manage these stewardship program's development, implementation, and dissemination.

Lowering barriers to naloxone access through a student-led harm reduction program.

BACKGROUND: In recent years, the opioid crisis has had devastating effects on communities across the country. In the wake of 4 University of Southern California (USC) student overdose deaths in 2019, USC pharmacy students initiated a naloxone distribution program called NaloxoneSC. This program has distributed free naloxone kits, fentanyl test strips, and overdose prevention training to hundreds of students thus far. This report aims to provide a framework for the implementation of similar harm reduction programs at other universities. OBJECTIVES: NaloxoneSC partnered with USC Student Health to implement a naloxone distribution program that expands access to naloxone and increases opioid overdose education within the USC community. SETTING: USC undergraduate campus and Health Sciences Campus. METHODS: Students can follow the steps for obtaining a naloxone kit listed on the NaloxoneSC website. Watching a 10-minute training video or attending a naloxone training workshop completes the opioid overdose education. The kit is picked up by the student from 1 of 2 USC Student Health Center locations, Engemann or Eric Cohen. Each kit is packaged with Narcan nasal spray and fentanyl test strips. RESULTS: In 1 year, the program received at least 320 naloxone kit requests. Demand for naloxone kits increased over time, and roughly 4 times as many students requested kits from Engemann than from Eric Cohen. Approximately 600 students have received opioid overdose education through NaloxoneSC. CONCLUSIONS: In 1 year, more than 300 USC students voluntarily requested naloxone kits from NaloxoneSC. These findings suggest a need for increased access to this resource on college campuses. Peer-to-peer education and naloxone kit distribution are feasible and effective strategies that help address public health concerns and reduce harm among university students. NaloxoneSC can serve as an example for other college campuses or entities to newly implement or expand their own harm reduction measures.

Providing Low-barrier Addiction Treatment Via a Telemedicine Consultation Service During the COVID-19 Pandemic in Los Angeles, County: An Assessment 1 Year Later.

BACKGROUND: Los Angeles County Department of Health Services provides medical care to a diverse group of patients residing in underresourced communities. To improve patients' access to addiction medications during the COVID-19 pandemic, Los Angeles County Department of Health Services established a low-barrier telephone service for DHS providers in March 2020, staffed by DATA-2000-waivered providers experienced with prescribing addiction medications. This study describes the patient population and medications prescribed through this service during its initial 12 months. METHODS: We performed a retrospective evaluation of a provider-entered call registry for the telephone consult line. Information was collected between March 31, 2020, and March 30, 2021. The registry includes information related to patient demographics, the reason for visit, and which addiction medications were prescribed. We conducted descriptive statistics in each of these domains. RESULTS: During the study period, 11 providers on the MAT telephone service logged 713 calls. These calls represented a total of 557 unique patients (mean age of 40 years, 75% male, 41% Latino, 49% experiencing homelessness). Most patients either had Medicaid insurance (77%) or were uninsured (20%). The most prescribed addiction medication was buprenorphine-naloxone (90%), followed by nicotine replacement therapy (5.3%), naltrexone (4.2%), and buprenorphine monotherapy (1.8%). CONCLUSION: A telephone addiction medication service is feasible to deliver low-barrier medications to treat addiction in underresourced communities, especially to individuals experiencing homelessness. This can mitigate but does not eliminate disparities in access to addiction medications for communities of color.

Buprenorphine and naloxone access in pharmacies within high overdose areas of Los Angeles during the COVID-19 pandemic.

BACKGROUND: Buprenorphine and naloxone are first-line medications for people who use opioids (PWUO). Buprenorphine can reduce opioid use and cravings, help withdrawal symptoms, and reduce risk of opioid overdose. Naloxone is a life-saving medication that can be administered to reverse an opioid overdose. Despite the utility of these medications, PWUO face barriers to access these medications. Downtown Los Angeles has high rates, and number, of opioid overdoses which could potentially be reduced by increasing distribution of naloxone and buprenorphine. This study aimed to determine the accessibility of these medications in a major urban city by surveying community pharmacies regarding availability of buprenorphine and naloxone, and ability to dispense naloxone without a prescription. METHODS: Pharmacies were identified in the Los Angeles downtown area by internet search and consultation with clinicians. Phone calls were made to pharmacies at two separate time points-September 2020 and March 2021 to ask about availability of buprenorphine and naloxone. Results were collected and analyzed to determine percentage of pharmacies that had buprenorphine and/or naloxone in stock, and were able to dispense naloxone without a prescription. RESULTS: Out of the 14 pharmacies identified in the downtown LA zip codes, 13 (92.9%) were able to be reached at either time point. The zip code with one of the highest rates of opioid-related overdose deaths did not have any pharmacies in the area. Most of the pharmacies were chain stores (69.2%). Eight of the 13 (61.5%) pharmacies were stocked and prepared to dispense buprenorphine upon receiving a prescription, and an equivalent number was prepared to dispense naloxone upon patient request, even without a naloxone prescription. All of the independent pharmacies did not have either buprenorphine or naloxone available. CONCLUSIONS: There is a large gap in care for pharmacies in high overdose urban zip codes to provide access to medications for PWUO. Unavailability of medication at the pharmacy-level may impede PWUO ability to start or maintain pharmacotherapy treatment. Pharmacies should be incentivized to stock buprenorphine and naloxone and encourage training of pharmacists in harm reduction practices for people who use opioids.

Changes in the availability of medications for opioid use disorder in prisons and jails in the United States during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, federal agencies relaxed buprenorphine prescribing restrictions including for incarcerated individuals. The impact of COVID-19 on the supply of MOUD in U.S. prisons and jails is not known. METHODS: We used cross-sectional national monthly data from the IQVIA National Sales Perspective (NSP) for the total volume of medicines supplied to city, county and state prisons and jails and other types of institutional facilities in the U.S. We measured the total monthly supply (or volume) as extended units (EUs) for MOUDs overall and by type. We used interrupted time series analysis to evaluate changes in monthly volume of MOUDs in prisons and jails and other types of facilities (hospitals, clinics and long-term care) before (January 2018-February 2020) and during the COVID-19 (March 2020-October 2020) pandemic. RESULTS: The availability of MOUD in jails and prisons increased by 471.3% between January 2018 (52,784 EU) and October 2020 (333,226 EU). This increase was largely driven by increased volume of buprenorphine/naloxone and was not observed in other institutional facilities, including hospitals, clinics and long-term care, and. Specifically, the mean monthly volume of buprenorphine/naloxone at prisons/jails increased every month before the pandemic by 1860 EU (95% CI, 1110-2360). In March 2020, the mean volume of buprenorphine/naloxone increased by 81,930 EU (95% CI, 59,040-104,820) per month, followed by a significant increase of 24,010 EU (95% CI 19,530-28,490) per month during the pandemic vs before the pandemic. CONCLUSION: These findings may indicate increased availability of buprenorphine/naloxone, a safe and effective MOUD, in prisons and jails since the start of the COVID-19 pandemic in the U.S. despite previous barriers in its use.

Prevalence and distribution of high-risk prescription opioid use in the United States, 2011-2016.

PURPOSE: Despite the efforts of many stakeholders to reduce the risk of opioid overdose, there is limited information on the prevalence of high-risk prescription opioid use in the US. METHODS: Descriptive analysis of a nationally representative 5% random sample of anonymized, longitudinal, individual-level prescription claims from IQVIA LRx between January 1, 2011 and December 31, 2016 among individuals ages 18 years or older that used a retail pharmacy. High-risk opioid use was defined as ≥50 morphine milligram equivalents per day and/or having concurrent dispensing of a benzodiazepine based on overlapping days of coverage. RESULTS: The prevalence of high-risk opioid use among adults in the US decreased from 12.0% in 2011 to 9.4% in 2016 (p < 0.01). Declines were most pronounced among individuals ages 18-35 years (10.9%-7.0%, 36.2% decline; p < 0.01) compared to individuals age 65 years or greater (10.5%-9.8%, 6.7% decline; p < 0.01). Declines in high-risk use prevalence were observed across 49 states, with only South Dakota experiencing an increase (+13.7% relative increase). Similar to earlier years, in 2016 50.9% of all high-risk use opioid users received all their opioid prescriptions from a single prescriber, and 71.1% used a single pharmacy to fill them. CONCLUSION: Despite clinically significant declines in high-risk opioid use, in 2016 nearly 1 in 10 adult retail pharmacy users remained at high-risk for opioid overdose in the US. Future clinical and policy interventions should consider targeting older adults with Medicare Part-D, including those using a single pharmacy to fill their opioid prescriptions.

Leveraging pharmacists to maintain and extend buprenorphine supply for opioid use disorder amid COVID-19 pandemic.

PURPOSE: Strategies for deploying clinical pharmacists to increase access to buprenorphine in inpatient, outpatient and transitional care, and community practice settings are described. SUMMARY: Access to medications for opioid use disorder (MOUD) is essential, but patients face many barriers when pursuing treatment and MOUD. The coronavirus disease 2019 (COVID-19) pandemic has compounded the opioid crisis and worsened outcomes by introducing new barriers to MOUD access. Many strategies to ensure continued access to MOUD have been described, but the role of leveraging pharmacists during the opioid/COVID-19 syndemic to improve medication access and outcomes remains underappreciated. Pharmacists, while both qualified and capable of liberalizing access to all forms of MOUD, may have the strongest impact by increasing access to buprenorphine. Herein, we present progressive strategies to maintain and extend buprenorphine access for patients with OUD through deployment of clinical pharmacists, particularly in the context of the COVID-19 pandemic, during which access may be further restricted. CONCLUSION: Leveraging pharmacists to extend access to MOUD, particularly buprenorphine, remains an underutilized strategy that should be implemented, particularly during the concurrent COVID-19 global pandemic.

Safety of Repeated Administration of Parenteral Ketamine for Depression.

The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to individuals for depression, and extracted reported adverse events. The survey was sent to 69 providers, of which 36 responded (52% response rate); after eliminating those that were incomplete, 27 were included in the analysis. The providers in the analysis collectively reported treating 6630 patients with parenteral ketamine for depression, one-third of whom received more than 10 treatments. Only 0.7% of patients experienced an adverse effect that required discontinuation of ketamine. Psychological distress during the treatment was the most frequent cause. Other adverse events were extremely rare (such as bladder dysfunction (0.1%), cognitive decline (0.03%) and psychotic symptoms (0.03%)). Among the 20 published reports of repeated parenteral ketamine treatments, rates of significant adverse events resulting in discontinuation were low (1.2%). The rate of adverse effects reported in the survey and the published literature is low, and suggests that long-term treatment of depression with ketamine is reasonably safe.

Dissociating the Clinical Role and Economic Value of Intranasal Esketamine.

DISCLOSURES: No funding supported the writing of this commentary. The author has nothing to disclose.

The effects of ketamine on suicidality across various formulations and study settings.

INTRODUCTION: Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality. METHODS: A review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference. RESULTS: A total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited. DISCUSSION: Ketamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.

Using the LACE Score as a Predictor of Clinical Outcomes in Patients Referred for Inpatient Palliative Care Consultation: A Single-Center Experience.

BACKGROUND: Readmissions and death for palliative care patients are common and costly outcomes for hospitals, patients, and/or caregivers. Predicting which patients are likely to be readmitted or die within 30 days would help allocate resources and aid in patient disposition planning. Few factors have been strongly correlated with predicting which patients will be readmitted or die within 30 days of hospital discharge. The LACE (Length of Stay, Acuity of admission, Charlson comorbidity index, Emergency department use) score has been validated in medical/surgical patients; however, it has not been evaluated in the palliative care population. OBJECTIVE: To evaluate the LACE score in palliative care population. DESIGN: This study was a single-center retrospective cohort design. SETTING/PATIENTS: Patients were identified based on their consultation to an inpatient palliative care service. MEASUREMENTS: Thirty-day readmissions, 30-day mortality, length of stay, acuity of admission, Charlson comorbidity index, emergency department utilization, and demographic information. RESULTS: The LACE score was not an accurate predictor of clinical outcomes in the palliative care population. Patients who were readmitted or died within 30 days tended to be younger. Patients who were readmitted within 30 days tended to have increased emergency department use in the previous 6 months. CONCLUSIONS: Our study demonstrates the LACE score may not be a sensitive predictor of clinical outcomes in our institution's palliative care patients. This may be due to the complexity of the required care in this population; thus, other factors should be investigated to determine accurate predictors of patient outcomes to better allocate resources.