Comparative Analysis of Deutetrabenazine and Valbenazine as VMAT2 Inhibitors for Tardive Dyskinesia: A Systematic Review.

Background: Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population. Methods: We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials.gov between January 2017 and October 2023, using the keywords "tardive dyskinesia" AND ("valbenazine" [all fields] OR " deutetrabenazine " [all fields]) AND "clinical trial". The reviewed articles were studied for efficacy and side effects. Results: An initial search yielded 230 articles, of which 104 were duplicates. Following the title and abstract screening, 25 additional articles were excluded. A full-text review resulted in the exclusion of 96 more articles. Ultimately, four double-blind clinical trials met the inclusion criteria. The deutetrabenazine studies demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo, with no difference in adverse events. The valbenazine studies showed favorable results in reducing TD symptoms and were well-tolerated. Discussion: The studies reviewed in this analysis underscore the potential of deutetrabenazine and valbenazine as valuable treatment options for TD in diverse populations. Both medications demonstrated significant improvements in AIMS scores, suggesting their effectiveness in managing TD symptoms. Additionally, they exhibited favorable safety profiles, with low rates of serious adverse events and no significant increase in QT prolongation, parkinsonism, suicidal ideation, or mortality. Conclusion: The studies reviewed highlight the promising efficacy and tolerability of deutetrabenazine and valbenazine as treatments for Tardive Dyskinesia, providing new hope for individuals affected by this challenging condition.

Management of OFF condition in Parkinson disease.

Parkinson disease (PD) impacts nearly 1 million individuals in the United States. Nearly every patient with PD will require therapy with dopamine in the form of levodopa as the disease progresses. In more advanced stages of the disease, patients will experience motor fluctuations and require adjustment to their medication regimens to maintain good control of their symptoms. During the last 10 years, several new therapeutic treatment options have come to the market to treat motor fluctuations and improve patient quality of life. Some of these agents represent additional options to previously available drug classes, such as the catechol-O-methyl transferase (COMT) inhibitor, opicapone, and monoamine-oxidase B-inhibitor (MAO-B inhibitor), safinamide, as well as new dosage forms for available therapeutics. One new agent, istradefylline, has a novel mechanism in the treatment of PD. The place in therapy for these newer therapeutic options will be explored through a series of patient cases. This article focuses on evidence-based recommendations for the use of these newer options in the management of patients experiencing OFF episodes.

The effect of the COVID-19 pandemic on the prescribing of opioid and opioid use disorder medications within an academic medical center in California.

Introduction: The COVID-19 pandemic impacted healthcare operations affecting many patients with chronic pain and substance use disorder. Our study aimed to evaluate the effects of the COVID-19 pandemic on opioid and opioid use disorder (OUD) medication prescribing practices within a large academic health system in southern California. Methods: This retrospective cohort study included patients who received a prescription for chronic opioids or therapy for OUD between November 1, 2019 and September 1, 2020. The date range was divided into five specific time periods during the pandemic: November through December 2019 (pre-COVID and reference period), January through February 2020 (early COVID), March through April 2020 (policy/guidance change period), May through June 2020 (early post-guidance period), and July through August 2020 (late post-guidance period). The primary outcome was change in morphine milligram equivalents (MME) prescribed. Secondary outcomes included encounter type, mode of prescription ordering, naloxone prescriptions, and urine drug screen obtainment. Results: The cohort included 100 patients divided among the designated time periods. Seventy-percent of patients received opioids for chronic non-malignant pain and 10% received therapy for OUD. Although there were numerical increases in MMEs prescribed, no significant changes were seen in the MMEs prescribed at any timepoint relative to the pre-COVID timeframe despite reduced in-person visits, increased video and telephone encounters and increased electronic prescription utilization. Subgroup analyses of those with chronic pain only or OUD had similar findings. Conclusion: It appears that, generally, prescribing practices were sustained despite the various phases of the pandemic including transitions to and from telemedicine.

Student perception of academic advising in a school of pharmacy.

OBJECTIVES: Literature assessing the optimal means of providing academic advisement in pharmacy education is limited. The objective of this study was to describe students' perception of advising within a school of pharmacy. METHODS: A 27-question survey was developed utilizing Qualtrics and sent to all students at one school of pharmacy. Baseline descriptive data regarding frequency and format of meeting with the assigned advisor were collected, as well as students' opinions of these meetings. KEY FINDINGS: Of 282 students who were sent the survey, 90 responded (31.9%). The majority of students preferred to meet with their faculty advisor in a group as compared with one-on-one (59 versus 29, 67%). Most students found the advisor/advisee relationship beneficial (n = 77, 85%). CONCLUSIONS: There was no statistically significant difference in student perception of the quality or value of advisor/advisee meetings between students who met in a group or one-on-one with their advisors.

Teaching Intellectual Humility Is Essential in Preparing Collaborative Future Pharmacists.

Interprofessional teams contribute significantly to patient care and safety. However, barriers to effective interdisciplinary collaboration have been identified, such as power dynamics and mistrust among team members, contrasting ideologies, interests and levels of engagement of clinicians, and disciplinary territoriality, which could negatively impact patient care. Teaching current health professional students behaviors and personal values that promote collaboration is critical in equipping them to function effectively in an interdisciplinary care setting. In this commentary, we put forward the idea that teaching intellectual humility is important in preparing collaborative future pharmacists. The core dimensions of intellectual humility, namely, open-mindedness, intellectual modesty, engagement, and corrigibility are important behaviors that could address the above-mentioned barriers, and promote successful interdisciplinary collaboration. Furthermore, we suggest strategies through which student pharmacists could be taught intellectual humility, mainly within the interprofessional education setting.

VMAT2 inhibitors for the treatment of hyperkinetic movement disorders.

Hyperkinetic movement disorders comprise a variety of conditions characterized by involuntary movements, which include but are not limited to tardive dyskinesia, chorea associated with Huntington's Disease, and tic disorders. The class of medications that have been used to treat these conditions includes Vesicular Monoamine Transporter-2 (VMAT2) inhibitors. In 2008, the FDA approved tetrabenazine as a treatment for chorea associated with Huntington's Disease. Optimization of the pharmacology of tetrabenazine has since led to the approval of two new VMAT2 inhibitors, deutetrabenazine and valbenazine. The objective of this review is to provide background on the role of VMAT in monoamine neurotransmission, the mechanism of VMAT2 inhibition on the treatment of hyperkinetic disorders (specifically tardive dyskinesia and chorea associated with Huntington's Disease), the pharmacology and pharmacokinetics of the commercially available VMAT2 inhibitors, and a summary of the clinical data to support application of these medications.

Implementation and results of a symptom-triggered opioid withdrawal protocol at a Veterans Affairs medical center.

INTRODUCTION: The Chillicothe Veterans Affairs Medical Center serves veterans from southern Ohio, Kentucky, and West Virginia, where the rates of non-medical opioid use are some of the highest in the nation. Prior to this project, there was not a standardized practice for the treatment of veterans undergoing opioid withdrawal at the facility. In May 2015, a symptom-triggered protocol was initiated to improve the quality of care and decrease the length of detoxification for veterans treated at the Chillicothe Veterans Affairs Medical Center. METHODS: This paper reflects a 2-phase project that took place from August 2014 through June 2016. Phase 1 focused on the development of a symptom-triggered opioid withdrawal protocol using the Clinical Opiate Withdrawal Scale for assessment and buprenorphine/naloxone or clonidine for treatment. Phase 2 was a retrospective cohort analysis comparing outcomes between group 1, before protocol initiation; group 2, after protocol initiation with clonidine; and group 3, after protocol initiation with buprenorphine/naloxone. The primary outcome assessed was length of detoxification (in days). Secondary outcomes included length of hospitalization (in days) for the index admission, outpatient substance abuse treatment program participation rates, and opioid sobriety rates at 3 months after detoxification. RESULTS: A statistically significant reduction in the duration of detoxification days was detected after protocol initiation in veterans who received buprenorphine/naloxone or clonidine in accordance with the protocol. DISCUSSION: This retrospective quality analysis supports the use of a symptom-triggered opioid withdrawal protocol using the Clinical Opiate Withdrawal Scale for assessment and clonidine or buprenorphine/naloxone for detoxification treatment.

Review of pharmacologic treatment in cluster A personality disorders.

INTRODUCTION: A personality disorder is a pervasive and enduring pattern of behaviors that impacts an individual's social, occupational, and overall functioning. Specifically, the cluster A personality disorders include paranoid personality disorder, schizoid personality disorder, and schizotypal personality disorder. Patients with cluster A personality disorders tend to be isolative and avoid relationships. The quality of life may also be reduced in these individuals, which provokes the question of how to treat patients with these personality disorders. The purpose of this review is to evaluate the current literature for pharmacologic treatments for the cluster A personality disorders. METHODS: A Medline/PubMed and Ovid search was conducted to identify literature on the psychopharmacology of paranoid personality disorder, schizoid personality disorder, and schizotypal personality disorder. There were no exclusions in terms of time frame from article publication or country of publication, in order to provide a comprehensive analysis; however, only articles that contained information on the cluster A disorders were included. RESULTS: Minimal evidence regarding pharmacotherapy in paranoid and schizoid personality disorders was found. Literature was available for pharmacologic treatment of schizotypal personality disorder. Studies evaluating the use of olanzapine, risperidone, haloperidol, fluoxetine, and thiothixene did yield beneficial results; however, treatment with such agents should be considered on a case-by-case basis. DISCUSSION: Most of the literature analyzed in this review presented theoretical ideas of what may constitute the neurobiologic factors of personality and what treatments may address these aspects. Further research is needed to evaluate specific pharmacologic treatment in the cluster A personality disorders. At this time, treatment with pharmacologic agents is based on theory rather than evidence.

Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers.

Hyperuricemia develops as early as 10 wk of gestation in women who later develop preeclampsia. At this time the invasive trophoblast cells are actively remodeling the uterine spiral arterioles, integrating into and finally replacing the vascular endothelial lining. In the nonpregnant population uric acid has several pathogenic effects on vascular endothelium. We therefore sought to examine the effects of uric acid (0-7 mg/dl) on trophoblast cell invasion through an extracellular matrix using an in vitro Matrigel invasion assay. We also assessed trophoblast integration into a uterine microvascular endothelial cell monolayer in a trophoblast-endothelial cell coculture model. Additionally, we addressed the importance of redox signaling and trophoblast-induced endothelial cell apoptosis. Uric acid elicited a concentration-dependent attenuation of trophoblast invasion and integration into a uterine microvascular endothelial cell monolayer. The attenuated trophoblast integration appeared to be the result of reduced trophoblast-induced endothelial cell apoptosis, likely through the intracellular antioxidant actions of uric acid. In a test of relevance, pooled serum (5% vol/vol) from preeclamptic women attenuated the ability of trophoblast cells to integrate into the endothelial cell monolayers compared with pooled serum from healthy pregnant controls, and this response was partially rescued when endogenous uric acid was previously removed with uricase. Taken together these data support the hypothesis that elevations in circulating uric acid in preeclamptic women contribute to the pathogenesis of the disorder, in part, through attenuation of normal trophoblast invasion and spiral artery vascular remodeling.