Paliperidone-Associated Sialorrhea: A Case Report With Review of Current Literature.

PURPOSE/BACKGROUND: Antipsychotic-associated sialorrhea is a problematic adverse effect with potentially negative consequences on quality of life and medication adherence. While clozapine is the antipsychotic that is most associated with sialorrhea, there have been published reports of other second-generation antipsychotics associated with sialorrhea, including aripiprazole, olanzapine, quetiapine, and risperidone. Although drooling is mentioned within the package insert for paliperidone, to date there have been minimal published reports in which paliperidone is implicated as the offending agent. METHODS/PROCEDURES: Here, we present a case of sialorrhea in a 56-year-old man with schizoaffective disorder who had a supratherapeutic paliperidone level after both oral and intramuscular paliperidone use. FINDINGS/RESULTS: Paliperidone was ultimately cross tapered to aripiprazole, and the patient was given atropine drops and benztropine with resolution of the sialorrhea. We provide a review of the literature regarding the other available reports of paliperidone-associated sialorrhea, possible mechanisms behind pathophysiology, as well as reports from the World Health Organization and Food and Drug Administration adverse event reporting systems. IMPLICATIONS/CONCLUSIONS: Clinicians should be aware of the potential for paliperidone and other nonclozapine second-generation antipsychotics to be associated with sialorrhea, especially given the increased frequency of their use for a variety of psychiatric disorders.

Istradefylline: A novel agent in the treatment of "off" episodes associated with levodopa/carbidopa use in Parkinson disease.

The current gold standard for treatment of Parkinson disease (PD) is levodopa/carbidopa (L/C), but long-term treatment frequently results in motor complications, such as wearing-off and motor fluctuations (eg, dyskinesia, "on-off" phenomenon). Istradefylline is a new drug with a unique pharmacologic profile that was approved by the FDA for use as adjunctive treatment to L/C in adult patients with PD experiencing "off" episodes. The drug was shown to reduce "off" time in 4 randomized, double-blind, placebo-controlled studies. The most common adverse effects are dyskinesia, dizziness, constipation, nausea, hallucinations, and insomnia. Unlike many drugs that treat PD, istradefylline is a nondopaminergic drug that exerts its effects via adenosine A2A receptor antagonism. The major drug interactions involve inhibitors or inducers of CYP3A4 as well as tobacco smoking via induction of CYP1A1. Istradefylline is taken once daily as a 20- or 40-mg dose, except in cases involving drug interactions or hepatic impairment. The cost of the drug is relatively expensive, which has implications for Medicare and private insurance coverage. Istradefylline is an alternative option to dopaminergic drugs such as dopamine agonists, monoamine oxidase B inhibitors, and catechol-O-methyltransferase inhibitors as an adjunct to L/C in patients with motor fluctuations, but clinical use will further define its role in treatment of PD.

Addressing the Conflict Between Promoting Wellness, Perpetuating Mental Illness Stigma and Making Psychiatric Pharmacy Education Less Intense.

One in five Americans has a diagnosable mental illness, and pharmacists encounter these patients daily. This commentary addresses the conflict between the profession's wellness movement and its ongoing contribution to mental illness stigma. The need for improved pharmacist wellness is based on the profession's risk for burnout and development of related mental illness. The presence of stigma towards patients with mental illness among pharmacists is multi-factorial and complex. Risk of those within the profession perpetuating mental illness stigma could be diminished by developing pharmacy curricula that provide greater opportunities for students to learn more completely about mental illness, how to effectively engage persons with mental illness, and how to take care of themselves, express vulnerability, and talk about mental illness. While reducing mental illness stigma through curricular revision is best achieved through in-person learning experiences, elective coursework and cocurricular activities may also help achieve this goal. Examples of evidence-based best practices are provided.

Association between concentrations of chromium in drinking water and mortality due to suicide in Alabama.

Preclinical studies and clinical data from case series and placebo-controlled trials suggest that chromium might have antidepressant effects. We conducted an observational study in order to assess the association between concentrations of chromium in drinking water and mortality due to suicide in Alabama. Publicly available databases were used to determine both county-level concentrations of chromium in drinking water and county-level rates of mortality due to suicide in the years 2005-2015. Data analyses comparing county-level concentrations of total chromium in drinking water with mortality rate due to suicide were conducted using a two-tailed nonparametric Spearman's rank correlation, with statistical significance set at p ≤ 0.01 and 99% confidence interval. Sub-analyses were conducted examining males, females, whites, and blacks/other minorities. There were no statistically significant findings concerning concentrations of chromium and suicide rate in the general population (p = 0.35, r = -0.12); however, there was a statistically significant inverse relationship between the concentration of chromium and suicide deaths in whites (p = 0.009, r = -0.32). There were no statistically significant findings in the remaining demographic subgroups. Chromium in drinking water might have a protective effect against mortality due to suicide, at least in the Caucasian population.

Pharmacists' attitudes, interest, and perceived skills regarding suicide prevention.

INTRODUCTION: Pharmacists have been called upon to be involved in suicide prevention efforts, but little is known regarding their attitudes, interest, and perceived skills in the area. METHODS: The study was a voluntary, anonymous survey of pharmacists who attended a large end-of-year continuing education program sponsored by a school of pharmacy. The survey included the Attitudes to Suicide Prevention (ASP) Scale, items concerning interest in suicide prevention, and items from the suicide skills section of the Suicide Knowledge and Skills Questionnaire. RESULTS: The survey was completed by 227/297 (76.4%) pharmacists. The percentage of participants who expressed interest in direct involvement, indirect involvement, and receiving training in suicide prevention were 25%, 46%, and 56%, respectively. The mean total score on the ASP was 32.2 ± 5.5. Approximately 4% to 8% of participants agreed that they had the requisite training, skills, or support/supervision to engage and assist suicidal patients, and 22% agreed to feeling comfortable asking their patients direct and open questions about suicide. The ASP scores and items relating to perceived skills were correlated with interest in direct involvement in suicide prevention. DISCUSSION: There were some positive findings, but overall, the pharmacists who participated in this survey felt unprepared to be frontline clinicians in suicide prevention efforts. Further studies should be conducted to determine if these findings are generally reflective of the broader pharmacy community. If the profession is to have a serious role in suicide prevention, then adequate suicide prevention training for pharmacy students and pharmacists may be necessary.

The Association Between Lithium in Drinking Water and Incidence of Suicide Across 15 Alabama Counties.

BACKGROUND: Recent studies have shown that lithium may be effective at reducing suicide at low doses, such as those found in drinking water. AIMS: The purpose of this study was to compare suicide rates with natural lithium levels in the drinking water of various Alabama counties. METHOD: Five drinking water samples from each of 15 Alabama counties were collected. Lithium levels were measured in triplicate using an inductively coupled plasma emission spectrophotometer and compared with suicide rate data for the period 1999-2013. Age, gender, and poverty were evaluated as potential confounding variables. RESULTS: The average measured lithium concentrations ranged from 0.4 ppb to 32.9 ppb between the counties tested. The plot of suicide rate versus lithium concentration showed a statistically significant inverse relationship ( r = -.6286, p = .0141). Evaluation of male-only suicide rate versus lithium concentration data also yielded significant results; however, the female-only rate was not significant. Age standardized suicide rates and poverty when individually compared against lithium levels were also found to be statistically significant; unexpectedly, however, poverty had a parallel trend with suicide rate. CONCLUSION: Lithium concentration in drinking water is inversely correlated with suicide rate in 15 Alabama counties.

An internet-based survey in Japan concerning social distance and stigmatization toward the mentally ill among doctors, nurses, pharmacists, and the general public.

Stigma associated with psychiatric disorders tends to be manifested as negative attitudes or behavior toward the mentally ill. It has negative influences, such as leading to difficulty in establishing trust-based relationships and interfering with medical treatment. In order to reduce such stigma, it is necessary to clarify its extent and characteristics in healthcare professionals. Considering this, an Internet-based questionnaire survey was conducted, involving doctors (n = 186), nurses (n = 161), and pharmacists (n = 192) in comparison with the general public (n = 331), and using the Whatley Social Distance Scale (WSDS) and Index of Attitudes toward the Mentally Ill (IATM) as stigma-related indices. Median total WSDS scores and interquartile range were as follows: doctors: 15.5(12.0-18.0), nurses: 14.0(12.0-16.5), pharmacists: 15.0(13.0-17.0), and the general public: 16.0(13.0-18.0). Similarly, median IATM scores were as follows: doctors: 39.0(36.0-42.0), nurses: 39.0(37.0-43.0), pharmacists: 40.0(36.0-42.0), and the general public: 37.0(33.0-41.0). IATM scores were significantly higher in the professional groups than the general public group. Both healthcare professionals and the general public with prior exposure to mental illness were more favorable attitudes toward the mentally ill. Especially among healthcare professionals, they working in psychiatric departments were more favorable attitudes. These results suggest that the stigma of healthcare professionals toward the mentally ill was shown to have a smaller and relatively favorable attitude than that of the general public. In order to correct the stigma it was suggested that a good contact experience with the patient such as work and training in psychiatry is effective.

D-cycloserine in the treatment of posttraumatic stress disorder.

INTRODUCTION: Posttraumatic stress disorder (PTSD) is a common and serious psychiatric illness. Exposure therapy is a type of cognitive behavioral therapy that is considered a first-line treatment option for PTSD. D-cycloserine (DCS) enhances fear extinction/exposure therapy in patients with various anxiety disorders, presumably via its N-methyl-D-aspartate receptor partial agonist effects. The aim of this paper is to review the published literature regarding the efficacy of DCS in the treatment of PTSD. METHODS: A literature search for placebo-controlled trials assessing the use of DCS as the primary study drug in PTSD was conducted for trials published before June 2015 using PubMed, Ovid International Pharmaceutical Abstracts, and www.clinicaltrials.gov. The search terms were variations of "cycloserine" and "posttraumatic stress disorder." RESULTS: Seven clinical trials were analyzed, including 2 trials comparing DCS with placebo as add-on treatment to ongoing stable pharmacotherapy and 5 trials that compared DCS with placebo given prior to exposure therapy. D-cycloserine as adjunctive therapy showed no benefit in 1 trial and limited benefit in the other. As an enhancement of exposure therapy, DCS showed beneficial effects in 1 trial, detrimental effects in 1 trial, and inconclusive effects in 3 trials. DISCUSSION: Current literature does not adequately support the use of DCS as adjunctive therapy without psychotherapy, but limitations of the 2 studies that exist make firm conclusions unfeasible. D-cycloserine might have a role in augmentation of exposure therapy. Future studies should consider receptor selectivity, administration time with respect to peak cerebrospinal fluid concentrations, number of exposure therapy sessions, and dose.

Effects of a psychiatric clinical rotation on pharmacy students' attitudes toward mental illness and the provision of pharmaceutical care to the mentally ill.

INTRODUCTION: Previous studies have found ineffectiveness of psychiatric clinical rotations to change pharmacy students' attitudes toward mental illness, but those studies had various limitations that cast doubt on this conclusion. METHODS: Pharmacy students who participated in a psychiatric clinical rotation over a 2-year time frame were invited to complete a survey at the beginning and end of their rotation. The survey included scales that measured attitudes toward dangerousness, social distance, stigmatization, suicide prevention, and provision of pharmaceutical care. RESULTS: Forty-one (100%) students participated in the study. Statistically significant positive changes in total scale scores from pre-rotation to post-rotation were seen in the areas of stigmatization toward patients with schizophrenia (P = .02), attitudes toward suicide prevention (P = .05), and provision of pharmaceutical care services to patients with schizophrenia (P < .00001) and depression (P = .0006). There were no statistically significant changes on the total scores of the other scales, but there was a moderate improvement in stigmatization toward patients with depression. DISCUSSION: Pharmacy students' participation in a psychiatric clinical rotation failed to have a major impact on their social distance from mentally ill patients. Findings were mixed in regards to stigmatization of mentally ill patients. However, pharmacy students' attitudes toward suicide prevention and providing pharmaceutical care services to mentally ill patients were significantly improved by participation in a psychiatric clinical rotation. Preceptors in the clinical setting should consider including educational techniques that address pharmacy students' attitudes toward mental illness, as improvement in such attitudes may further enhance their willingness to provide pharmaceutical care services.

Sleep quality among pharmacy students.

OBJECTIVE: To determine the quality of sleep among pharmacy students in the didactic portion of the curriculum at one school of pharmacy. METHODS: The study consisted of an anonymous, voluntary survey that included the Pittsburgh Sleep Quality Index (PSQI), a self-rated instrument that measures sleep habits for a month. RESULTS: The survey was completed by 253 students. Students in the lower grade point average (GPA) category had higher scores on 2 of 7 components of the PSQI and on the global score. Poor sleep quality, indicated by a global PSQI score of greater than 5, was reported by 140 students. The rate of poor sleeping was higher among students in the lower GPA category. CONCLUSION: Poor sleep quality was pervasive among surveyed pharmacy students in the didactic portion of the pharmacy school curriculum, especially among those with lower GPAs.

Attitudes of matriculating first-year pharmacy students toward a mandatory, random drug-screening program.

OBJECTIVE: To determine the attitudes of incoming pharmacy students toward a mandatory, random urine drug-screening program. METHODS: This was an anonymous, voluntary survey of students at the McWhorter School of Pharmacy (MSOP) using an instrument composed of 40 items. The instrument was administered during orientation week prior to the session during which the policies and procedures of MSOP's drug-screening program were to be discussed. RESULTS: The survey instrument was completed by all 129 (100%) students in the class. Two-thirds of the students were aware of MSOP's drug-screening program prior to applying, but only a few felt uneasy about applying to the school because of the program. The greatest concerns expressed by the students included what would happen if a student unintentionally missed a drug screen or was busy with other matters when called for screening, how much time a drug-screening would take, and the possibility of false-positive drug screen results. The vast majority of students agreed with statements regarding the potential benefits of drug testing. Students who consumed alcohol in a typical week and those with current or past use of an illegal substance held less favorable attitudes toward MSOP's mandatory drug-screening program compared with students who did not share those characteristics. CONCLUSION: Although there were definite concerns expressed regarding pragmatic issues surrounding drug screening, the first-year pharmacy students held generally favorable opinions about the school's mandatory drug-screening program.

Experience with a drug screening program at a school of pharmacy.

Substance use and abuse among pharmacy students is a concern of pharmacy schools, boards of pharmacy, and training sites alike. Pharmacy students must complete approximately 30% of their academic coursework in experiential settings such as community pharmacies, hospitals, and other health systems as part of any accredited pharmacy school's curriculum, and these training sites are starting to require drug testing of pharmacy students as part of their contractual agreements with schools of pharmacy. The authors describe the implementation of a mandatory random urine drug screening program at their school as well as the changes that occurred owing to assessment of the program. The authors report the basic results to date of the drug screening program. The authors also speculate on secondary benefits of the drug screening program. Finally, the authors describe current and future evaluations that they are undertaking regarding this program.

Pregabalin for the treatment of generalized anxiety disorder.

OBJECTIVE: To evaluate the efficacy and tolerability of pregabalin in the treatment of generalized anxiety disorder (GAD). DATA SOURCES: A search of PubMed (1966-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was conducted using the MeSH and free-text terms pregabalin, anxiety disorders, and anxiety. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified through the search were evaluated for inclusion. Only randomized controlled trials involving the use of pregabalin for the treatment of GAD were included in the review. DATA SYNTHESIS: Eight published trials were identified through the search strategy. Successful treatment of GAD with pregabalin versus placebo and active comparators has been reported in clinical trials. Pregabalin lowered total Hamilton Rating Scale for Anxiety scores within 1 week and was effective against both somatic and psychic subcomponents. In 1 controlled clinical trial, pregabalin was found to be effective in patients aged 65 years and older. Another trial demonstrated improved relapse rates when pregabalin, compared with placebo, was used for up to 6 months. The most commonly experienced adverse events were somnolence, dizziness, headache, and dry mouth. CONCLUSIONS: Available evidence suggests that pregabalin is effective and well tolerated in the treatment of GAD. As somnolence and dizziness are common adverse effects, caution should be used in elderly patients. Pregabalin rapidly relieves anxiety, a benefit that it may have over many other currently available therapeutic options besides benzodiazepines. While not a first-line therapy in GAD, pregabalin offers another treatment option in patients who do not respond to or who suffer intolerable adverse effects from other agents.

Ramelteon for Insomnia Related to Attention-Deficit/Hyperactivity Disorder (ADHD).

OBJECTIVES: This study evaluated the efficacy of ramelteon for insomnia in adult subjects with ADHD. EXPERIMENTAL DESIGN: For this randomized, double-blind, placebo-controlled crossover trial, 8 mg of ramelteon was given nightly, within three hours of bedtime, to ADHD-insomnia subjects confirmed by DSM-IV-TR, ADHD-RS, MINI, and clinical interview. All subjects underwent two weeks each of ramelteon and placebo. Objective sleep measures were obtained by actigraphy. Subjective measures included: the Epworth Sleepiness Scale (ESS) and ADHD-RS. PRINCIPAL OBSERVATIONS: Of 36 subjects entering the study, 58% met criteria for circadian rhythm sleep disorder (CRSD), delayed sleep phase type. During ramelteon period, mid-sleep time, an indicator of circadian phase, occurred significantly earlier, by ~45 minutes compared to placebo period. An association was noted between the magnitude of the sleep phase advance and the timing of ramelteon administration in relationship to sleep start time, but did not reach statistical significance; maximal efficacy was noted 1.5 hours before bedtime. Paradoxically, ramelteon marginally, but significantly increased sleep fragmentation and ESS scores compared to the placebo state. CONCLUSIONS: Ramelteon is efficacious in maintaining an earlier sleep/wake cycle in adults with ADHD and CRSD but can have paradoxical fragmenting effects on sleep and exacerbate daytime sleepiness. In the presence of a circadian rhythm disorder, the usual dosing and timing parameters for ramelteon need to be carefully considered.

Metabolic consequences of using low-dose quetiapine for insomnia in psychiatric patients.

Quetiapine is frequently prescribed for insomnia that is comorbid with psychiatric disorders, but there has been no documentation of metabolic adverse effects associated with this practice. The objective of this study was to document changes in weight, body mass index, and waist circumference that occurred when low-dose quetiapine was used at bedtime for insomnia. The study was a retrospective chart review conducted at a community mental health center. Patients were non-elderly (19-65 years old) psychiatric patients who received quetiapine at < or =200 mg at bedtime for the explicit indication of insomnia. Forty-three patients were included in the study. Weight and BMI increased by an average of 4.9 lb. (P = 0.037) and 0.8 points (P = 0.048), respectively. Males experienced statistically significant increases in weight and BMI, and Caucasians experienced a statistically significant increase in BMI. There were no significant differences between baseline and endpoint metabolic parameters when examined by baseline BMI, age category, psychiatric diagnosis, or concomitant psychotropic medication. Despite the low doses typically used when quetiapine is prescribed for insomnia, metabolic adverse effects can occur and should be considered in the overall benefit to risk analysis.

Prazosin for treatment of nightmares related to posttraumatic stress disorder.

PURPOSE: The efficacy of prazosin for the treatment of posttraumatic stress disorder (PTSD)-related nightmares is reviewed. SUMMARY: PTSD is an anxiety disorder that can occur after experiencing or witnessing a life-threatening event, such as military combat, natural disasters, terrorist attacks, serious accidents, or violent personal assaults. The event that induced PTSD is often relived through nightmares or flashbacks. Sleep disturbances affect approximately 70% of patients with PTSD. Several medications have been evaluated for reducing PTSD-related nightmares, with limited success. Prazosin is a centrally and peripherally acting alpha(1)-adrenergic antagonist whose mechanism of action, favorable adverse-effect profile, and low cost make it a promising agent for the treatment of PTSD. To date, two case reports, two chart reviews, three open-label trials, and two placebo-controlled trials have been published documenting the efficacy and safety of prazosin in the treatment of PTSD-related nightmares. Therapy with prazosin resulted in a reduction in nightmares in patients with both combat- and noncombat-related trauma. A therapeutic benefit occurred with prazosin dosages as low as 1 mg daily, and suppression of nightmare symptoms occurred within one week of prazosin initiation. The most frequently reported adverse event was orthostatic hypotension. The variability in the populations studied (e.g., combat, noncombat, recent traumatic experiences) leaves additional unanswered questions that must be addressed in large, randomized, controlled trials. CONCLUSION: Prazosin appears to be a promising and well-tolerated agent for the management of PTSD-related nightmares. Further well-designed trials are warranted to establish its place in the treatment of PTSD.

Clinical and pharmacoeconomic evaluation of switch to olanzapine in veterans with schizophrenia or schizoaffective disorder.

BACKGROUND: Second-generation atypical antipsychotics improve the outcome of patients with schizophrenia, although studies of their cost efficacy in comparison to first-generation conventional antipsychotics have yielded mixed results. OBJECTIVES: This study examines the cost effectiveness outcome of olanzapine treatment in veterans with schizophrenia (n 5 22) or schizoaffective disorder (n 5 4). METHODS: Health-care utilization and costs associated with prospective olanzapine treatment were compared with those of retrospective first-generation neuroleptic treatment in a mirror-image design. RESULTS: The analysis of variance with repeated measures for the Positive and Negative Syndrome Scale (PANSS; n 5 22) showed a significant main effect of olanzapine treatment (p , .025), and the effect was of medium-to-large size (h2 5 .13). The PANSS-positive subscale (p , .005) and the PANSS general subscale (p , .005) significantly decreased, but the PANSS negative subscale did not change. The quality of life survey (n 5 21) significantly increased (p , .025), and the effect size was large (h2 5 .14). For VA outpatient and inpatient care, study patients incurred an average cost difference of 2$1,289 (NS) and 2$6,682 (NS), respectively. Combining inpatient and outpatient VA care, patients incurred an annual difference of 2$7,971 per patient (NS). These numerically lower costs were due, in part, to a slower growth rate in outpatient encounters (p 5 .013), lower overall cost per outpatient encounter (p 5 .008), and a lower overall inpatient encounter rate (p 5 .005). CONCLUSIONS: Olanzapine treatment resulted in improvements in positive and general psychiatric symptoms, as well as quality of life. Negative symptoms did not change significantly. Though not statistically significant, the postbaseline health-care costs and utilization declined.

Faculty attitudes and scholarly productivity resulting from a seminar course.

OBJECTIVES: To determine faculty attitudes toward a professional seminar course for PharmD students, document scholarly production derived from the course, and ascertain whether that scholarly production or other faculty characteristics affected attitudes toward the course. METHODS: Faculty members served as facilitators for pharmacy students enrolled in a professional seminar course. A 34-item survey instrument intended to identify faculty attitudes toward the course and document scholarly productivity was developed. All 40 faculty facilitators involved in the course were asked to complete the survey instrument. RESULTS: Of the 30 (75%) faculty members who completed the survey instrument, 20 had an overall positive attitude toward the course. Faculty members had generated approximately 90 peer-reviewed scholarly works over a 9-year period as a result of the course. Significant associations were found between faculty members' attitudes toward the course and academic rank, academic department, and scholarly production derived from the course. CONCLUSIONS: Faculty members who had advanced academic rank, an appointment in the pharmacy practice department, and scholarly productivity as a result of serving as a facilitator for a Professional Seminar Course were more likely to have positive attitudes toward the course.