Evaluation of generational influences among 4th year pharmacy students and experiential preceptors.

INTRODUCTION: The purpose of this study was to evaluate the influence generational categories may have on commonalities among pharmacy students and their pharmacist preceptors during advanced pharmacy practice experiences (APPEs). METHODS: Multiple-choice surveys aimed at evaluating generational characteristics were sent to pharmacy students and their preceptors during the first three APPEs. Questions focused on six key areas: preferred learning/teaching style, view of career/work, communication style, view of technology, life outlook, and personal characteristics. Each response corresponded to a generational category (Veteran, Baby Boomer, Generation X, Millennial). Students and preceptors were instructed to apply each question to themselves; students then applied each question to their preceptor, while preceptors applied the questions to students. RESULTS: Twenty-six percent of students and 35% of preceptors completed at least one generational survey. Students selected the option that corresponded to their actual generational category significantly more often compared to preceptors (2.133 ±â€¯0.815 vs. 1.632 ±â€¯1.132, p = 0.007). Although none of the respondents belonged to the Veteran category, responses corresponding to this generation represented the second highest number of responses selected by students and preceptors alike. CONCLUSIONS: Students and preceptors identified with characteristics outside their actual generational category. In addition, both groups selected options such as working to make a difference that may correlate more with people who have chosen pharmacy as a profession. Pharmacist awareness of generational similarities may lead to a more successful student-preceptor relationship.

Treatment of dyslipidemia with statins by primary care providers in Veterans with and without chronic Hepatitis C.

OBJECTIVE: The purpose of this study was to describe the current use of statins in United States (US) veterans at W. G. Hefner Veterans Affairs Medical Center (VA Salisbury) with chronic hepatitis C virus (HCV) compared to those without chronic HCV and to examine why statin use may be avoided in this population. METHODS: In this retrospective chart review, eligible participants were veterans enrolled in VA Salisbury primary care services who were at least 18 years of age with a diagnosis of dyslipidemia. Veterans must have had a lipid panel drawn between April 25, 2011 and October 25, 2011. The primary outcome of this study was to determine the prevalence of statin use among US veterans with HCV. A secondary outcome was to determine the proportion of subjects reaching goal LDL levels. RESULTS: A total of 157 subjects were included in this study. A significant difference in statin use was seen between subjects with and without HCV (54% vs. 83%, p <0.001). Although there were a greater number of subjects on statins in the non-HCV group, there was not a significant difference in the proportion of subjects reaching their LDL goal between the two groups. CONCLUSION: Among veterans, statins are used less frequently in patients with HCV compared to those without HCV. Both groups had similar achievement of LDL goals, though.

Prospective measurement of a problem-based learning course sequence.

OBJECTIVE: To measure the effect, over time, of a 2-year problem-based learning (PBL) sequence on the skills, knowledge, and abilities it was designed to develop and enhance. DESIGN: At the start of each PBL semester, students were provided a "work sample" case with a main medical issue not previously covered in the curriculum. A standardized form containing 6 sections (hypotheses, learning issues to investigate, how hypotheses ruled in/out, primary-problem identification, plan, and goals of plan) was completed for each case. To rate student performance, investigators used a standardized form with 5-point Likert scale. ASSESSMENT: Sixty-seven students who completed 4 assessments were included in data analyses. Scores significantly improved for each semester compared with baseline. Minimal significant differences were observed among semesters 2, 3, and 4. CONCLUSION: The 2-year PBL sequence improved students' performance compared with baseline, but the performance ceiling observed in our study requires further investigation.

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.

The efficacy and safety of newer anticonvulsants in patients with dementia.

Anticonvulsants are a class of medications that have received considerable interest as possible treatments in patients with behavioural disturbances in dementia. The role of these medications for such a use remains controversial. The current paper reviews the published evidence surrounding the safety and efficacy (i.e. as a behavioural and cognitive treatment) of newer anticonvulsants in patients with dementia. A MEDLINE, International Pharmaceutical Abstracts, PsycINFO and clinicaltrials.gov search through to December 2011 was conducted for anticonvulsants that have received regulatory approval since 1996. Studies reporting behavioural or cognitive outcomes in patients with dementia were included. Nine trials involving only four medications met selection criteria and were included: levetiracetam (n = 4), oxcarbazepine (n = 1), topiramate (n = 2) and zonisamide (n = 2). Levetiracetam may have a role in the treatment of behavioural symptoms in dementia but study limitations substantially hinder the strength of such a recommendation. Oxcarbazepine and topiramate, based on limited data, do not appear to be effective treatments of behavioural symptoms in dementia. A lack of trials do not allow for conclusions to be made regarding zonisamide. From a cognitive standpoint, levetiracetam was the anticonvulsant most examined in patients with dementia, it appears to have less deleterious effects than some anticonvulsants. Limited data are available on the safety of these medications in elderly patients; however, studies completed thus far have demonstrated some adverse events that are more common or problematic with the use of these drugs in this patient population (i.e. somnolence, dizziness, hyponatraemia, weight loss).

Valproic acid in dementia: does an optimal dose exist?

Valproic acid is widely used in the treatment of behavioral disturbances in patients with dementia; however, there is uncertainty about its dosing and studies have reported mixed findings. The current article examines published trials of valproic acid in the treatment of patients with dementia to identify whether an optimal dosing strategy exists. Secondarily, valproic acid dosing from published studies is compared with a real-world 5-year sample of valproic acid prescribing. Twenty studies met selection criteria and were included in the review. Based primarily on uncontrolled trials and the current retrospective study, valproic acid serum levels between 40 and 60 mcg/mL and relatively low doses (ie, 7-12 mg/kg per d) are associated with improvements in agitation in some patients with dementia. At the same time, similar valproic acid levels produced no significant behavioral improvements in most placebo-controlled studies and led to substantial side effects in some patients. Considerable trial design differences exist between controlled and uncontrolled trials. Overall, valproic acid appears to have limited efficacy as monotherapy in many patients with dementia. Its optimal role may be in combination with other psychotropics as a treatment of agitation associated with dementia.

Antipsychotic polypharmacy among patients admitted to a geriatric psychiatry unit.

OBJECTIVES: This study describes the prevalence of antipsychotic polypharmacy in patients admitted to a geriatric psychiatry unit, compares polypharmacy by psychiatric diagnosis, explores predictors of polypharmacy, and examines changes in antipsychotic polypharmacy from baseline to discharge. METHODS: A retrospective examination was made of patients admitted to an inpatient geriatric psychiatry ward between 2006 and 2010. All patients with a diagnosis of schizophrenia, bipolar disorder, or dementia prescribed a regularly scheduled antipsychotic for at least 1 month prior to admission were included. RESULTS: Of the 416 patients meeting selection criteria, nearly 13% were prescribed antipsychotic polypharmacy at the time of admission. Quetiapine was the antipsychotic most commonly involved in polypharmacy. By discharge, the rate of antipsychotic polypharmacy had decreased to 8% (X=4.74, df=1, p=0.03). Patients with a history of a severe mental illness were significantly more likely to have been prescribed antipsychotic polypharmacy compared with those with only a diagnosis of dementia (X=14.67, df=1, p=<0.001). Living situation and psychiatric diagnosis were significant predictors of antipsychotic polypharmacy. CONCLUSION: Older adults admitted to a geriatric psychiatry ward on a scheduled antipsychotic were commonly prescribed more than one antipsychotic. This was most likely in patients living in a facility (e.g., assisted living, skilled nursing, long-term care) and in those patients with a severe mental illness. A better understanding of the efficacy and safety of antipsychotic polypharmacy in older adults, especially those with dementia, is necessary in order to use these medications rationally.

A module on death and dying to develop empathy in student pharmacists.

OBJECTIVE: To implement an integrated module on death and dying into a 15-week bioethics course and determine whether it increased student pharmacists' empathy. DESIGN: Students participated in a 5-week death and dying module that included presentation of the film Wit, an interactive lecture on hospice, and a lecture on the ethics of pain management. ASSESSMENT: Fifty-six students completed the 30-item Balanced Emotional Empathy Scale (BEES) before and after completing the module and wrote a reflective essay. Students demonstrated an appreciation of patient-specific values in their essay. Quantitative data collected via BEES scores demonstrated significant improvement in measured empathy. CONCLUSION: A 5-week instructional model on death and dying significantly increased student empathy.

Quetiapine for sleep in patients with dementia.

OBJECTIVE: to examine the use of quetiapine for sleep in patients with dementia admitted to a geriatric psychiatry ward. DESIGN: retrospective cross-sectional study (January 2007 to December 2009). SETTING: geriatric psychiatric unit located near a metropolitan city in North Carolina. PARTICIPANTS: all patients admitted with a diagnosis of dementia who were also receiving quetiapine were eligible. One hundred one patients met the criteria and were included in the study. INTERVENTION: none. MAIN OUTCOME MEASURES: descriptive statistics defining quetiapine prescribing. Based on a priori criteria, quetiapine was considered to be used for sleep if it were prescribed: 1) only at bedtime, as needed, for sleep, 2) once daily, only at bedtime, or 3) multiple times daily, but with at least 75% of the daily dose administered at bedtime. RESULTS: forty-three of the 101 patients included in the study were prescribed quetiapine, probably for sleep. Quetiapine, when used as a sedative-hypnotic, was generally employed at doses between 50 mg and 100 mg nightly. Several published studies report beneficial sleep-promoting effects of quetiapine and other atypical antipsychotics for primary and secondary sleep complaints; however, most of these trials involve young and middle-aged adults, have diagnostic variability, and are limited methodologically. CONCLUSION: quetiapine prescribed as a sedative-hypnotic in patients with dementia, while common, is understudied and not without risk.

Use of psychostimulants in patients with dementia.

OBJECTIVE: To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia. DATA SOURCES: Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed. STUDY SELECTION AND DATA EXTRACTION: All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate. DATA SYNTHESIS: Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities. CONCLUSIONS: Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.

Comparison of a pharmacist-managed lipid clinic: in-person versus telephone.

OBJECTIVE: To compare the effectiveness of an in-person versus telephone-based pharmacist-managed lipid clinic. METHODS: Retrospective examination of a pharmacist-managed lipid clinic conducted at a Veterans Affairs medical center between September 2005 and March 2008. The clinical pharmacist educated, monitored, recommended nonpharmacologic treatment, and prescribed lipid-lowering medications using an in-person or telephone-based clinic style. The primary outcomes were to compare the two clinic styles on the percent of patients who reached their low-density lipoprotein (LDL) cholesterol goal and the absolute percent of LDL cholesterol reduction. RESULTS: 157 patients with coronary artery disease or its risk equivalent were enrolled in the pharmacist-managed lipid clinic. Overall, patients experienced a mean 27% reduction in LDL cholesterol levels from baseline, and 76% reached their LDL cholesterol goal. No significant differences in the percent of patients reaching their LDL cholesterol goal or absolute percent reduction in LDL cholesterol levels were found between the in-person and phone-based clinics. A trend toward phone clinic patients achieving their goal LDL cholesterol levels more quickly was noted. CONCLUSION: Both in-person and phone-based pharmacist-managed lipid clinics offer effective methods to improve the cholesterol levels of patients. Phone-based clinics may offer more advantages in efficiency for pharmacists and their patients and the potential to deliver care in a wider variety of pharmacy settings.

Certolizumab pegol: a TNF-{alpha} antagonist for the treatment of moderate-to-severe Crohn's disease.

OBJECTIVE: To review certolizumab pegol for the treatment of moderate-to-severe Crohn's disease (CD). DATA SOURCES: Clinical studies were identified through MEDLINE (1966-October 1, 2009), bibliographies of articles, International Pharmaceutical Abstracts, clinicaltrials.gov, fda.gov, and New Drug Approval documents (www.accessdata.fda.gov). Search terms were CDP 870, certolizumab pegol, Cimzia, Crohn's disease, and inflammatory bowel disease. STUDY SELECTION AND DATA EXTRACTION: Human studies describing pharmacology, pharmacokinetics, efficacy, and safety of certolizumab pegol were identified. Phase 2 and Phase 3 randomized controlled trials and observational studies were reviewed, with emphasis given to Phase 2 and Phase 3 trials. DATA SYNTHESIS: Certolizumab pegol is a tumor necrosis factor-alfa (TNF-alpha) antagonist, approved for the treatment of moderate-to-severe CD that is failing conventional therapy. It is an antigen-binding fragment (Fab') portion of an immunoglobulin G antibody attached to a polyethylene glycol moiety. In 2 Phase 3 randomized, placebo-controlled trials, certolizumab pegol was effective in inducing clinical response compared with placebo. Common adverse effects during clinical trials were upper respiratory tract infection, urinary tract infection, and arthralgia. Serious infection occurred in 3% of patients. The 4 published controlled trials for the use of certolizumab pegol in the treatment of CD share similar limitations with other studies of TNF-alpha antagonists including high placebo response, natural course of disease fluctuation, and the use of Crohn's Disease Activity Index to assess outcomes. However, certolizumab pegol is an effective agent for adults with moderate-to-severe CD with less than optimal response to conventional therapy. Long-term efficacy and safety data are unavailable. Certolizumab pegol and adalimumab, unlike infliximab, can be self-administered. CONCLUSIONS: With similarity in cost and the lack of head-to-head comparisons, patient and physician preference may determine choice of TNF-alpha antagonist.

Agomelatine treatment of major depressive disorder.

OBJECTIVE: To review the efficacy, safety, pharmacologic, and pharmacokinetic data of agomelatine to better understand its potential role in the treatment of patients with major depressive disorder. DATA SOURCES: A MEDLINE search (1966-October 2008) was conducted using the following terms: agomelatine, antidepressant, S20098, melatonin, serotonin, 5-HT(2C), MT, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, receptor binding, depression, major depressive disorder, and mood disorder. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Randomized, controlled trials involving humans were prioritized in the review. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. DATA SYNTHESIS: Agomelatine, a potent agonist at type 1 and 2 melatonin receptors, selectively inhibits serotonin. It is extensively metabolized via cytochrome P450 isoenyzmes 1A1, 1A2, and 2C9 to metabolites with less activity than the parent drug. Five randomized controlled studies were identified that examined the efficacy and safety of agomelatine in major depressive disorder. In general, agomelatine was found to produce significant improvements in depressive symptoms compared with placebo on many, but not all, rating scales. Three of the trials had active comparator arms (ie, venlafaxine, paroxetine). In these 3 investigations, agomelatine produced effects on depressive symptoms similar to those of the comparator drugs. A small number of studies have demonstrated sleep benefits with the use of agomelatine in depressed patients. Positive findings also exist for the use of agomelatine in seasonal affective disorder and bipolar depression. The most common adverse effects reported with agomelatine use were headache, nasopharyngitis, and gastrointestinal complaints. The magnitude of agomelatine-related adverse effects appears to be at least similar to some currently marketed antidepressants. CONCLUSIONS: Overall, agomelatine is a promising and well-tolerated medication for the treatment of major depressive disorder. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy and safety of agomelatine.

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.

Adherence and persistence to typical and atypical antipsychotics in the naturalistic treatment of patients with schizophrenia.

OBJECTIVE: To compare adherence and persistence to typical versus atypical antipsychotics and between specific atypical agents in the usual care of schizophrenia and to examine the association between adherence and persistence. METHOD: Data were drawn from a 3-year prospective, nonrandomized, noninterventional study of schizophrenia conducted during 1997-2003. Initiators on haloperidol, risperidone, olanzapine, quetiapine, and clozapine with at least 1 year of follow-up were included (n = 878). Adherence (Medication Possession Ratio, MPR) and persistence (time to all-cause medication discontinuation) were assessed using medical record prescription information. Analyses employed multivariate statistics adjusted for group differences. RESULTS: Overall, 58% of the patients were deemed adherent (MPR >80%). Adherence rates were higher: for atypical (59.4%) than typical antipsychotics (34.5%, p < 0.001), for clozapine (77%) than each comparator excluding olanzapine (p < 0.01), and for olanzapine (64%) than risperidone (57%, p = 0.027) and quetiapine (52%, p = 0.019). Differences between risperidone and quetiapine were not statistically significant. Adherence and persistence were highly correlated (r = 0.957, p < 0.001). CONCLUSION: In the usual care of schizophrenia, medication adherence and persistence appear to be highly correlated and to significantly differ between typical and atypical antipsychotics and among atypical agents. The choice of antipsychotic may play a meaningful role in patients' adherence to and persistence with antipsychotic medications.

Antipsychotic polypharmacy trends among Medicaid beneficiaries with schizophrenia in San Diego County, 1999-2004.

OBJECTIVE: This study examined trends and costs of second-generation antipsychotic polypharmacy among Medicaid beneficiaries with schizophrenia in San Diego County. METHODS: Medicaid data were used to identify 15,962 persons with schizophrenia receiving antipsychotic medications between 1999 and 2004. The yearly proportion of beneficiaries receiving second-generation antipsychotic polypharmacy, duration of polypharmacy, inpatient admissions, and pharmaceutical costs were examined. RESULTS: The proportion of clients receiving second-generation antipsychotic polypharmacy increased from 3.3% in 1999 to 13.7% in 2004, whereas annual antipsychotic medication costs increased from $4,128 to $5,231 (2004 dollars). Among those receiving second-generation polypharmacy, the percentage receiving second-generation polypharmacy for 12 months increased from 5.1% to 14.4%, and the percentage hospitalized increased from 7.2% to 9.0%. CONCLUSIONS: The prevalence of long-term second-generation antipsychotic polypharmacy and its associated costs increased substantially between 1999 and 2004. Prescribing antipsychotic polypharmacy is an unproven and costly strategy that if left unchanged could lead to administrative efforts to cut costs and dictate practice.

Cardiovascular medication prescribing in older adults with psychiatric disorders.

OBJECTIVES: To examine the appropriateness of cardiovascular (CV) medication prescribing of patients admitted to a geriatric psychiatry ward. Secondary aims included examining: 1) if differences in CV medication prescribing existed between admission and discharge and 2) if differences in CV medication prescribing existed between patients with and without dementia. DESIGN: Cross-sectional study. SETTING: Inpatient geriatric psychiatry unit within a regional medical center. PATIENTS: 197 patients admitted between June 2005 and May 2006. INTERVENTIONS: Changes in CV medication prescribing from admission to discharge. MEASURES AND RESULTS: On admission, the percent of patients receiving appropriate CV medications for general CV prevention, atrial fibrillation, coronary-artery disease, and heart failure ranged from 33% to 56%. With the exception of the treatment of heart failure, no significant improvements in appropriate CV medication prescribing were noted at the time of discharge. No differences in CV medication prescribing were found between patients with and without dementia. CONCLUSION: Despite the known benefits of numerous CV medications in older adults, many patients admitted to a geriatric psychiatry ward were not prescribed optimal pharmacotherapeutic regimens on admission or had their medications changed by the time of discharge.

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.

A prospective study of risk factors for nonadherence with antipsychotic medication in the treatment of schizophrenia.

OBJECTIVES: This study aimed to prospectively identify the best single predictor and the best set of predictors of risk for nonadherence with anti-psychotic medication in the treatment of patients with schizophrenia. METHOD: We used data from 1579 patients in a 3-year, prospective, naturalistic, nonrandomized, multisite study of schizophrenia patients conducted from July 1997 to September 2003 (U.S. Schizophrenia Care and Assessment Program). Adherence with any oral antipsychotic medication was assessed using patient-reported medication adherence and an indirect adherence measure based on medical record prescription information. Patients who reported poor medication adherence or had a medication possession ratio < or = 80% (percentage of days with prescriptions for any oral antipsychotic) during the first year after enrollment were defined as nonadherent (N = 296, 18.8%). Thirty-nine previously reported potential risk factors of nonadherence with antipsychotic medication were assessed at enrollment with valid and reliable measures. Risk factors represented patient-, environment-, and treatment-related domains, including sociodemographics, symptom severity, substance use, threat to safety of self and others, other illness-related factors, need for supervision, medication-related adverse events, and prior medication-utilization patterns. RESULTS: The best single predictor of future nonadherence was nonadherence during the 6 months prior to enrollment (odds ratio = 4.1, 95% confidence interval = 3.1 to 5.6, p < .001). The best set of predictors of nonadherence, ordered by strength of association, included prior non-adherence, recent illicit drug use, recent alcohol use, prior treatment with antidepressants, and greater patient-reported, medication-related cognitive impairment. CONCLUSION: Nonadherence with antipsychotic medication is associated with a well-defined set of risk factors that can be used to identify patients who are predisposed to poor adherence.