Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: A systematic review.

OBJECTIVES: The U.S. Food and Drug Administration recently approved lofexidine, an α-2-adrenergic agonist, as the first non-opioid medication for mitigation of opioid withdrawal symptoms. Clonidine, an α-2-adrenergic agonist, historically was used off-label for this indication. This review aimed to evaluate the effectiveness of lofexidine versus clonidine for mitigation of opioid withdrawal symptoms and to discuss the current role of lofexidine in the management of patients at risk of experiencing opioid withdrawal. DATA SOURCES: MEDLINE/PubMed, EBSCO, and CENTRAL were searched using the terms "lofexidine," "clonidine," and "opioid withdrawal." STUDY SELECTION: The literature search included English-language studies involving administration and prescription of lofexidine and clonidine for the management of opioid withdrawal symptoms in adults. Data sources were searched to include articles published between October 1993 and May 2019. DATA EXTRACTION: Three independent reviewers analyzed the title and abstract of studies to identify studies involving comparisons of lofexidine with clonidine for mitigation of opioid withdrawal symptoms. Reviewers were initially blinded to the individual determinations. Results were then unblinded and discussed among reviewers. RESULTS: Of the 110 citations screened, 5 articles were included. One study demonstrated a statistically significant reduction in opioid withdrawal symptom severity with lofexidine compared with clonidine, whereas the other 4 studies showed no significant difference. Three studies reported the completion of opioid detoxification treatment, with no significant differences seen. In 1 study that compared lofexidine with placebo, lofexidine caused significant hypotension, bradycardia, and pupillary constriction. Three studies showed significant adverse effects of hypotension and symptoms of feeling unwell with clonidine compared with lofexidine. CONCLUSION: Lofexidine appears equivalent in efficacy to clonidine, with fewer adverse effects, and it may have a limited role in the management of opioid withdrawal symptoms. However, cost, detoxification venue, and value of other preferred treatment modalities may affect the comparative efficacy of lofexidine to other agents.

Levomilnacipran: A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder.

OBJECTIVE: To provide a clinical overview of the antidepressant levomilnacipran. DATA SOURCES: Articles were identified by searching the MEDLINE, PubMed, Cochrane Library, and Clinicaltrials.gov databases through March 2014 using the keyword levomilnacipran. The manufacturer provided additional information from unpublished phase II and phase III trials. STUDY SELECTION AND DATA EXTRACTION: Any clinical trial conducted for at least 3 weeks and published in the English language was selected for review. Additional documentation, including the product dossier, package insert, pharmacokinetic studies, and poster presentations supplied by the manufacturer, was also evaluated. DATA SYNTHESIS: Levomilnacipran is the more potent enantiomer of milnacipran. It is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), dosed from 20 to 120 mg daily for the treatment of major depressive disorder (MDD). Efficacy and tolerability were established during 3 phase III randomized, double-blind placebo-controlled trials finding levomilnacipran to be significantly more efficacious than placebo in reduction of Montgomery-Åsberg Depression Rating Scale scores. It is not known whether this agent is more efficacious than other antidepressants because direct comparison studies have not been conducted as of the time of this review. CONCLUSIONS: Levomilnacipran demonstrates efficacy and tolerability for short-term treatment of MDD in adults. Available evidence does not strongly indicate that there is a specific subpopulation of patients who would benefit from levomilnacipran over currently available SNRIs. Full characterization of the agent's place in therapy alongside multiple other agents with similar mechanisms and efficacy requires trials with longer duration and active comparators.

Effects of age on metacognitive efficiency.

Humans have a capacity to become aware of thoughts and behaviours known as metacognition. Metacognitive efficiency refers to the relationship between subjective reports and objective behaviour. Understanding how this efficiency changes as we age is important because poor metacognition can lead to negative consequences, such as believing one is a good driver despite a recent spate of accidents. We quantified metacognition in two cognitive domains, perception and memory, in healthy adults between 18 and 84years old, employing measures that dissociate objective task performance from metacognitive efficiency. We identified a marked decrease in perceptual metacognitive efficiency with age and a non-significant decrease in memory metacognitive efficiency. No significant relationship was identified between executive function and metacognition in either domain. Annual decline in metacognitive efficiency after controlling for executive function was ∼0.6%. Decreases in metacognitive efficiency may explain why dissociations between behaviour and beliefs become more marked as we age.

The Write Stuff: The Development of a Medical Writing Pharmacy Residency Elective.

THE PROBLEM: Effective medical writing requires a mastery of many skills including those of data interpretation, literature evaluation, written communication, and leadership. A number of these skills are considered educational goals and objectives for residents by the American Society of Health-System Pharmacists, yet preceptors and residents oftentimes face challenges in gaining competency, confidence, and success in medical writing. INNOVATION: A structured yet individualized plan for medical writing, including idea creation, peer reviewing, manuscript preparation, and team management for post-graduate year two pharmacy residents was implemented as an elective learning experience. RESULTS: Feedback from residents participating in the elective was positive. Each of the two residents who participated produced a manuscript that was subsequently published. CONCLUSION: Though data is limited by number of residents that have completed this learning experience, this longitudinally designed elective has potential benefits and barriers to execution that should be considered, but may be an excellent opportunity to develop critical skills in scholarly endeavors for residents and preceptors alike.

Impact of Intersession Course Remediation on NAPLEX/PCOA Scores in an Accelerated Doctor of Pharmacy Program.

Objective. To compare Pharmacy Curriculum Outcomes Assessment (PCOA) scaled scores and North American Pharmacist Licensure Examination (NAPLEX) pass rates in students who completed a two-week intersession remediation or repeated a course with the scaled scores and pass rates of students who did not require any form of didactic remediation and did not have to repeat a course. Methods. Data examined for this study included NAPLEX/PCOA scores, NAPLEX pass/fail status, and remediation history for students at one college of pharmacy. Students from the graduating classes of 2016, 2017, and 2018 were organized into four groups: non-remediation, one course remediation and no repeats, more than one course remediation and no repeats, and one or more course repeats. Differences were analyzed using linear regression, logistic regression, and Pearson correlations. Results. The PCOA scores for students in the remediation groups were significantly lower than scores for students in the non-remediation groups, with a reduction of 37.8 to 50.9 points from the expected non-remediators' score. The NAPLEX scores for students who remediated more than one course or repeated one or more courses were 16-20 points lower compared to students who did not remediate. The likelihood of a student failing the NAPLEX was also not significantly lower for students who remediated one course but was significantly lower for other remediation groups. Conclusion. Although single course remediation in this curricular model appears to have minimal impact on NAPLEX outcomes and may be an acceptable intervention for many students, additional support and interventions may be warranted for students who qualify for remediation in multiple courses and/or for repeating a course.

Intersession Remediation to Minimize Attrition in a Three-Year Pharmacy Program.

Objective. To describe an intersession remediation process in an accelerated three-year Doctor of Pharmacy (PharmD) program and to determine if the remediation process reduced attrition rates, including program withdrawals, progression to advanced pharmacy practice experiences (APPEs), and on-time graduation rates. Methods. Attrition was defined as dismissal, withdrawal, leave of absence, and/or change in graduation date. Progression data from students who matriculated between 2008 to 2016, with data available through spring 2017, were analyzed for number of course failures and successful intersession remediation. Other factors such as pharmacy year (first or second year), course subject, and course repeats were evaluated to characterize successful remediation attempts and identify elements that foster student success. Results. Of the 812 matriculated students across the time period analyzed, 18% (n=146) failed at least one didactic course (defined as course average <69.5%). Overall, 74.7% (n=109) of the students who failed a course remediated, with 75.2% (n=82) of those able to remediate being successful, remaining on-time for graduation. If students who remediated were instead required to repeat coursework, the college attrition rate would have averaged over 10 percentage points higher for the time period analyzed than the actual rate of 13.4%. Conclusion. Our study demonstrated that the majority of students who qualified for remediation were successful and graduated on time. Further studies in this area are needed to fully elucidate the effect of remediation processes on learning and retention of knowledge and skills.

Evaluation of perceptions and knowledge of mental illness in the United States through crowdsourcing.

INTRODUCTION: Crowdsourcing is a method of data collection with possible benefits in assessing perceptions of mental illness in a large US population. METHODS: The objective was to describe perceptions and trends of stigma surrounding mental illness in the United States using crowdsourcing. An online survey was conducted evaluating adults in the United States recruited via the online resource Amazon Mechanical Turk. Questions evaluated demographics and perceptions of mental illness. Survey data were adjusted for demographic variables and compared via logistic regression. RESULTS: Respondents (n = 1422) were predominately 18 to 30 years of age (n = 743; 52.3%) and white (n = 1101; 77.4%). Over half reported an individual close to them had mental illness (n = 932; 65.5%), and more than one quarter (n = 397; 27.9%) reported having a current or previous mental illness. Non-whites were less likely to agree that: medications are effective (odds ratio [OR] 0.63); they would be comfortable around a coworker with mental illness (OR 0.66); and mental illness is inheritable (OR 0.74). They are also more likely to agree that mental illness is preventable (OR 1.49). Individuals reporting mental illness were more likely to agree that medications (OR 1.34; 95% confidence interval 1.03 to 1.74) and talk therapy (OR 1.46; 95% confidence interval 1.12 to 1.90) are effective. Those reporting some or no college were more likely to agree that the United States has good access to mental health treatment. DISCUSSION: Crowdsourcing may be an effective way to obtain information regarding demographics, stigma, and mental illness. Personal experiences with mental illness, ethnicity, and educational level appear to continue to impact perceptions of mental illness.

The relationship between cognitive insight and depression in psychosis and schizophrenia: a review and meta-analysis.

Lack of insight is a commonly observed problem in patients with psychosis and schizophrenia. Clinical insight in patients has been associated with low mood. Cognitive insight is a recently defined concept, relating to the ability to self-reflect and the degree to which patients are over-confident regarding their interpretations of illness-related experiences, and is related to clinical insight. We therefore sought to investigate whether there is a positive relationship between cognitive insight and mood. A literature search identified 17 relevant papers published between 2004 and 2014. Our analysis indicated that there was a small but significant positive correlation between the composite index (CI) of the Beck Cognitive Insight Scale (BCIS) and depression scores, but this was driven by a significant positive relationship between depression and the BCIS self-reflection (SR) sub-scale, where low mood was related to higher SR scores. There was no significant relationship between the self-certainty sub-scale and depression. Post-hoc analysis indicated that different depression scales did not significantly affect the relationship with SR. Our results support the idea that cognitive insight is significantly related to mood in schizophrenia, and the effect size is similar to that between clinical insight and mood. Potential applications of this knowledge into treatment and rehabilitation are discussed and a model of cognitive insight is proposed.

More work on lack of awareness and insight in healthy people and psychiatric patients will assist model building.

We comment on the work of Mograbi and Morris and their newly developed Cognitive Awareness Model in terms of metacognition and awareness of disability in health aging, dementia, and psychosis. It is suggested that further research comparing implicit awareness of disability and objective metacognitive processes would be useful for theory development, as well as further understanding cognitive models of insight in the clinical domain.