The effects of mirtazapine on sleep in patients with major depressive disorder.

BACKGROUND: Mirtazapine is a commonly used antidepressant with a well-known ability to produce sedation. At the same time, its sleep-promoting effects in patients with major depressive disorder (MDD) are relatively unclear. The purpose of this article is to provide clinicians with a detailed review of mirtazapine's sleep effects in patients with MDD. METHODS: A literature search was conducted for studies involving mirtazapine in depressed patients that specifically assessed sleep. RESULTS: Twenty-three studies met selection criteria and were included in this review. Of the 15 studies that included a general assessment of sleep, all noted improvement from baseline with mirtazapine. Twelve of the 23 trials were randomized, blinded, and controlled. Mirtazapine was superior to placebo but did not clearly differentiate itself from other antidepressants, with the exception of venlafaxine. Eight studies used detailed measures of sleep and consistently reported that mirtazapine produced significant improvement in sleep efficiency, total sleep time, and sleep quality. Few investigations combined detailed assessments of sleep along with a comparator antidepressant. CONCLUSION: Mirtazapine is an antidepressant with sleep-promoting effects significantly greater than placebo, similar to tricyclic antidepressants, and somewhat similar to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. These effects must be balanced with mirtazapine's ability to cause sedation-related side effects.

Hypnosedative-induced complex behaviours : incidence, mechanisms and management.

A number of news items and case reports describing complex behaviours (e.g. sleep driving, sleep cooking, sleep eating, sleep conversations, sleep sex) associated with the use of hypnosedative medications have recently received considerable attention. Regulatory agencies examining these reports have subsequently issued warnings regarding the potential of hypnosedative agents to produce complex behaviours. Despite these warnings, little is known about the likelihood, presentation, treatment or prevention of hypnosedative-induced complex behaviours. The purpose of this review is to evaluate the published evidence regarding the clinical presentation, incidence, mechanism and management of sleep-related behaviours induced by nonbenzodiazepine receptor agonists (NBRAs).Review of the literature identified ten published case reports of NBRA-induced complex behaviours involving 17 unique patients. Fifteen of the 17 patients described in the case reports had taken zolpidem, one had taken zaleplon and one had taken zopiclone. The complex behaviours most commonly reported were sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping. Elevated serum concentrations resulting from increased medication dose or drug-drug interactions appeared to play a role in some but not all cases. Sex, age, previous medication exposure and concomitant disease states were not consistently found to be related to the risk of experiencing a medication-induced complex behaviour.From a pharmacological standpoint, enhancement of GABA activity at GABAA receptors (particularly alpha1-GABAA receptors) is a possible mechanism for hypnosedative complex behaviours and amnesia. Evidence suggests that complex behaviour risk may increase with both dose and binding affinity at alpha1-GABAA receptors. The amnesia that accompanies complex behaviours is possibly due to inhibition of consolidation of short- to long-term memory, suggesting that the risk may extend to non-GABAergic hypnosedatives. While amnesia and GABA-related receptor actions are the most frequently discussed mechanisms for complex behaviours in the literature, they do not fully explain such behaviours, suggesting that other mechanisms and factors probably play a role.A number of potential strategies are available to manage or prevent hypnosedative-induced complex behaviours. These include lowering the dose of, or stopping, the offending hypnosedative, switching to a different hypnosedative, treating patients with other classes of medications, using nonpharmacological treatment strategies for patients with sleep disorders, examining drug regimens for potential drug interactions that may predispose patients to experiencing complex behaviours, administering hypnosedative medications appropriately and selecting patients more carefully for treatment in terms of their likelihood of experiencing medication adverse effects.

A preliminary model for faculty workload for a highly integrated curriculum delivered by team-based learning.

INTRODUCTION: We detail the process of developing a workload calculation model (WCM) for a highly integrated curriculum delivered by team-based learning, rationale for workload multipliers, and preliminary results of our effort to implement the WCM. METHODS: Our WCM includes teaching, service, and scholarship, with a time buffer. The WCM utilizes multipliers for most work activities (teaching and service). For other activities, a fixed number of hours per year was used. The WCM was set up using Microsoft Excel. The development of the WCM was an iterative process in collaboration with the school's Faculty Affairs Committee, each department, and then individually with all faculty members. RESULTS: The WCM had three sections. A section each for teaching and service workload calculations and a dashboard section to summarize workload calculations per department that added in time for scholarship and a buffer calculation (to allow flexibility for faculty). Teaching included classroom, experiential, and academic advising, all of which had unique multipliers. Service included committee work at all levels and student organization advising. A fourth section for time spent at individual faculty practice sites. Calculations were kept consistent between departments for most activities. CONCLUSION: We developed a novel WCM to accommodate all of the major areas of workload for faculty at a private institution. The unique approach to building it included representing teaching in a highly integrated curriculum delivered via team-based learning and creating a buffer category to allow for workload individualization. The WCM is actively used in our school to proactively manage workload.

Assessing Emotionally Intelligent Leadership in Pharmacy Students.

Objective. To determine the frequency distribution of pharmacy students across Emotionally Intelligent Leadership Inventory (EILI) measures. Methods. The EILI was administered to 235 pharmacy students at two schools. The instrument was systematically compared to the 2013 CAPE Outcomes and analyzed by confirmatory factor analysis. Results. The EILI has primary connections with pharmacy competencies related to interprofessional communication and leadership. The three facets of the EILI were verified for internal consistency (Context, α=.78; Self, α=.74; Others, α=.79). Student scores were the highest for the consciousness of self facet, with a mean score of 31.4 out of 40. Conclusion. The EILI shows promise as an instrument for use in assessing pharmacy students' emotional intelligence and leadership skills.

Deliberate Integration of Student Leadership Development in Doctor of Pharmacy Programs.

The CAPE 2013 Outcomes answered the call for increased student leadership development (SLD) by identifying leadership as a desired curricular goal. To meet this outcome, colleges and schools of pharmacy are advised to first identify a set of SLD competencies aligned with their institution's mission and goals and then organize these competencies into a SLD framework/model. Student leadership development should be integrated vertically and horizontally within the curriculum in a deliberate and longitudinal manner. It should include all student pharmacists, begin at the point of admission, and extend beyond extracurricular activities. The school's assessment plan should be aligned with the identified SLD competencies so student learning related to leadership is assessed. To accomplish these recommendations, a positive environment for SLD should be cultivated within the school, including administrative backing and resources, as well as support among the broader faculty for integrating SLD into the curriculum.

Including Emotional Intelligence in Pharmacy Curricula to Help Achieve CAPE Outcomes.

The importance of emotional intelligence (EI) for effective teamwork and leadership within the workplace is increasingly apparent. As suggested by the 2013 CAPE Outcomes, we recommend that colleges and schools of pharmacy consider EI-related competencies to build self-awareness and professionalism among students. In this Statement, we provide two examples of the introduction of EI into pharmacy curricula. In addition, we provide a 4-phase process based on recommendations developed by EI experts for structuring and planning EI development. Finally, we make 9 recommendations' to inform the process of including EI in pharmacy curricula.

Variations in parthenolide content and daily dose of feverfew products.

Variations in the parthenolide content of feverfew products available to consumers were studied. Feverfew products were analyzed for the content of parthenolide, the purported active component. The actual weight of feverfew was determined only in those products containing dried feverfew leaf. The total daily doses of feverfew leaf and parthenolide were calculated by using the instructions on each product label. Parthenolide content was determined by high-performance liquid chromatography. The quantity of feverfew leaf in each capsule was similar to that stated on the label and ranged from 25 to 500 mg. Parthenolide content per dosage form varied 150-fold (from 0.02 to 3.0 mg), while percent parthenolide varied 5.3-fold (from 0.14% to 0.74%). If a person consumed the daily dose recommended on the label, intake of dried feverfew leaf would range from 225 to 2246 mg/day, a 10-fold variation, while intake of parthenolide would range from 0.06 to 9.7 mg/day, a 160-fold variation. Large variations were observed in the parthenolide contents and daily intake as recommended by the labeling in commercial feverfew products.

A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer.

Breast cancer remains a leading cause of disease and death among women throughout the world. Despite advances in drug therapy, development of novel and improved drugs for breast cancer continues to be of great interest. Lapatinib is a novel dual receptor tyrosine kinase inhibitor that is a selective and potent inhibitor of ErbB-1 and ErbB-2 tyrosine kinases, both of which are growth promoting factors overexpressed in some breast cancers. Cell-based assays have proven lapatinib to be a potent inhibitor of ErbB-1 and ErbB-2 activation and breast cancer cell proliferation. In pharmacokinetic studies, lapatinib has shown mostly linear elimination kinetics over the daily dose range of 10-1600 mg and is metabolized by CYP3A4/5 and CYP2C19. Phase I, II, and III clinical trials involving lapatinib as monotherapy or in combination have shown promise for the treatment of advanced and metastatic breast cancer. Drug-drug interactions may occur secondary to concomitant administration of either CYP450 inhibitors or inducers. While lapatinib appear to be a promising addition to breast cancer therapy, several questions remain to be answered before its optimal role is elucidated.

Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and drug interactions of lapatinib. DATA SOURCES: A PubMed search was conducted (1966-August 2005) using the following terms: lapatinib, GW572016, and dual tyrosine kinase inhibitor. Additional information sources included meeting abstracts, clinical trial data, and bibliographies from articles identified through PubMed. STUDY SELECTION AND DATA EXTRACTION: Preclinical and clinical trials that evaluated lapatinib in cell culture, animal models, and human subjects were selected from the data sources. Pivotal in vitro data and all in vivo data published regarding lapatinib were included. DATA SYNTHESIS: The development of tyrosine kinase inhibitors has resulted from a search for targeted cancer therapeutics made possible by recent gains in our understanding of tumor cell biology. Lapatinib is a dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor and human epidermal growth factor receptor-2 autophosphorylation, leading to suppression of proliferation pathways of solid tumors. Lapatinib has shown clinical activity in solid tumors, with the most notable in advanced or metastatic breast cancer, including tumors refractory to trastuzumab. It has a mild adverse effect profile, with the most common adverse events being diarrhea and rash. CONCLUSIONS: Lapatinib has novel, dual tyrosine kinase inhibitory properties selective for factors overexpressed in some solid tumors. Results from preclinical and Phase I/II trials indicate activity in the treatment of solid tumors, especially advanced or metastatic breast cancer. Application for approval is anticipated pending results of ongoing Phase III trials.