Aneja, Alka; Rahman, Atiq; Megna, James; Freemont, Wanda; Shiplo, Mohammed; Nihilani, Nikil; Lee, Kathy
Chlorpromazine, haloperidol, fluphenazine, clozapine, risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole are antipsychotics commonly used in psychiatric medicine. Approximately one third of pregnant women with psychotic symptoms use antipsychotics at least once. This review will discuss the effects of antipsychotic use during pregnancy and lactation on the fetus and infant. Although adequate and well-controlled studies have not been done in any one of these antipsychotic drugs, animal studies have revealed evidence of teratogenic or embryo/fetotoxic effects in all of them. Toxicities include skeletal malformations, central nervous system (CNS) defects, cleft palate, cardiac abnormalities, decreased fetal growth, and fetal death. For example, in pregnant women, congenital malformations and perinatal death have been reported with chlorpromazine use. Both chlorpromazine and fluphenazine in monotherapy have been shown to cause extrapyramidal symptoms and respiratory distress in infants born to mothers treated with these medications. Haloperidol use during pregnancy has been linked to severe limb reduction defects. Effects of antipsychotic use in lactating mothers are mostly unknown. However, the use of chlorpromazine has been reported to result in drowsiness and lethargy in breastfed infants. Additionally, clozapine has been reported to cause sedation, decreased suckling, restlessness, irritability, seizures, and cardiovascular instability of infants were also reported with clozapine use in lactating mother. Use of antipsychotic drugs by pregnant and lactating mother may only be justified if the potential benefit outweighs the potential risk to the fetus. PMID:21152171
Neil, Wendy; Curran, Stephen; Wattis, John
older people. There is a need to redress this balance to ensure that the prescribing of antipsychotics in older people is evidence based.
Kishimoto, Taishiro; Watanabe, Koichiro; Uchida, Hiroyuki; Mimura, Masaru; Kane, John M; Correll, Christoph U
While combining antipsychotics is common in schizophrenia treatment, the literature on the reasons for antipsychotic polypharmacy (APP) is limited. We aimed to identify prescriber attitudes and rationales for APP in Japan where high APP utilization is reported. Two-hundred and seventeen psychiatrists participated in the survey, which assessed APP attitudes and behaviors. Prescribing APP to 47.7±24.7% (mean±S.D.) of their patients, psychiatrists reported that they were "moderately" concerned about APP. The most APP-justifiable factors were (1="not at all" to 5="extreme") cross titration (4.50±0.67), randomized controlled evidence (3.67±0.83), and treatment of comorbid conditions (3.31±0.83). Conversely, APP-discouraging factors were chronic side effects (4.14±0.64), difficulty determining cause and effect (4.07±0.74), and acute side effects (3.99±0.81). Comparing high to low APP prescribers (>50% vs. ≤50% of patients), no differences emerged regarding APP justification and concerns. In multivariate analyses, high APP use was associated with practice at a psychiatric hospital (OR: 2.70, 95% CI: 1.29-5.67, p=0.009), concern about potential drug-drug interactions (OR: 1.56, 95% CI: 1.04-2.35, p=0.031), and less reliance on case reports of APP showing efficacy (OR: 0.64, 95% CI: 0.44-0.92, p=0.017) (r(2)=0.111, p=0.001). High and low APP prescribers shared a comparable degree of justifications and concerns. Future research should examine the impact of cultural determinants on APP.
Becker, Edmund R; Constantine, Robert J; McPherson, Marie A; Jones, Mary Elizabeth
The rapid growth in the use of antipsychotic medications and their related costs have resulted in states developing programs to measure, monitor, and insure their beneficial relevance to public program populations. One such program developed in the state of Florida has adopted an evidence-based approach to identify prescribers with unusual psychotherapeutic prescription patterns and track their utilization and costs among Florida Medicaid patients. This study reports on the prescriber prescription and cost patterns for adults and children using three measures of unusual antipsychotic prescribing patterns: (1) two antipsychotics for 60 days (2AP60), (2) three antipsychotics for 60 days (3AP60), and (2) two antipsychotics for 90 or more days (2AP90). We find that over the four-year study period there were substantial increases in several aspects of the Florida Medicaid behavioral drug program. Overall, for adults and children, patient participation increased by 29 percent, the number of prescriptions grew by 30 percent, and the number of prescribers that wrote at least one prescription grew 48.5 percent, while Medicaid costs for behavioral drugs increased by 32 percent. But the results are highly skewed. We find that a relatively small number of prescribers account for a disproportionately large share of prescriptions and costs of the unusual antipsychotic prescriptions. In general, the top 350 Medicaid prescribers accounted for more than 70 percent of the unusual antipsychotic prescriptions, and we find that this disparity in unusual prescribing patterns appears to be substantially more pronounced in adults than in children prescribers. For just the top 13 adult and children prescribers, their practice patterns accounted for 11 percent to 21 percent of the unusual prescribing activity and, overall, these 13 top prescribers accounted for 13 percent of the total spent on antipsychotics by the Florida Medicaid program and 9.3 percent of the total expenditure by the
Machin, Anna; McCarthy, Lucy
Aims and method To detect any differences in the antipsychotic prescribing practices of consultant forensic psychiatrists working in different levels of secure care with patients diagnosed with schizophrenia, and to identify potential reasons for any differences. Prescribing data were collected from four secure hospitals within one National Health Service trust. A questionnaire was sent to consultant forensic psychiatrists working at those hospitals as well as those working in the trust's community forensic services. Results Consultants working in high security prescribed more oral antipsychotics than consultants working in medium and low security, who prescribed more depot antipsychotics, as established via the prescribing data. The questionnaire provided insight regarding the reasons for these preferences. Clinical implications There were differences in the antipsychotic prescribing practices of consultant forensic psychiatrists working in different levels of secure care, and, overall, the rate of depot antipsychotic prescribing was lower than might be expected. Although it was positive that the rate of polypharmacy was low when compared with earlier studies, the lower-than-expected rate of depot antipsychotic prescribing has clinical implications.
Aims and methods It is now well established that antipsychotic medications are associated with adverse effects such as metabolic dysfunction, hyperprolactinaemia and cardiac arrhythmias. We completed an audit cycle between 2008 and 2010 to assess whether the implementation of a high-visibility prompt and an educational programme would improve monitoring rates among patients prescribed regular antipsychotics admitted to a 59-bedded psychiatric hospital in West Sussex. Results There was an improvement in monitoring rates for most audit standards. The greatest improvement was seen in measurement of random plasma glucose and cholesterol levels. Rates improved irrespective of the risk of metabolic dysfunction. However, prolactin measurement remained static and the ECG recording deteriorated. Clinical implications There appears to be a growing awareness of the need to screen for metabolic dysfunction among patients prescribed regular antipsychotic medication. A high-visibility prompt and educational programme helps to increase monitoring rates. However, more needs to be done to improve the mortality and morbidity rates among this patient subpopulation. PMID:24381652
Murphy, Andrea L; Gardner, David M; Kisely, Steve; Cooke, Charmaine A; Kutcher, Stanley P; Hughes, Jean
There are significant controversies regarding rising antipsychotic prescription trends in children and adolescents. Many pharmacoepidemiology trend studies have been published, and interpretations of these data are helpful in explaining what is happening in prescribing practices, but not why these patterns exist. There is a lack of qualitative data in this area, and the experience of prescribing antipsychotics to children and adolescents has not been adequately researched. We conducted a qualitative study using an interpretive phenomenological analysis of physicians’ experiences of antipsychotic prescribing to children and adolescents. Prescribers participated in individual interviews and a focus group. We used a staged approach for data analysis of transcriptions. In all, 11 physicians including psychiatrists and general practitioners participated in our study. We identified themes related to context, role and identity, and decision-making and filtering. Struggles with health system gaps were significant leading to the use of antipsychotics as substitutes for other treatments. Physicians prescribed antipsychotics to youth for a range of indications and had significant concerns regarding adverse effects. Our results provide knowledge regarding the prescribers’ experience of antipsychotics for children and adolescents. Important gaps exist within the health system that are creating opportunities for the initiation and continued use of these agents. PMID:26614572
Larkin, Ian; Ang, Desmond; Avorn, Jerry; Kesselheim, Aaron S
The treatment of pediatric depression is controversial because it includes substantial prescribing of drugs for uses that have not been approved by the Food and Drug Administration ("off label") and are not evidence based. Some academic medical centers (AMCs) restrict "detailing" by pharmaceutical sales representatives, or the promoting of drugs directly to physicians via sales calls, to reduce the effect of such marketing on physician prescribing. With data from thirty-one geographically diverse AMCs and their affiliated hospitals, we used a difference-in-differences model to estimate the effect of anti-detailing policies on off-label prescribing of antidepressants and antipsychotics by pediatricians and by child and adolescent psychiatrists in the period January 2006-June 2009. We found that after the introduction of such policies, prescriptions for off-label use of promoted drugs fell by 11 percent, consistent with the ongoing presence of off-label marketing to physicians. Prescriptions for on-label use of promoted drugs fell by 34 percent after the adoption of the policies. Conversely, prescriptions for on-label use of nonpromoted drugs rose by 14 percent, and those for off-label use of nonpromoted drugs rose by 35 percent. These results suggest that pharmaceutical sales representatives promoted drugs not approved for pediatric use and that policies that restrict detailing by those representatives reduced such off-label prescribing.
Tungaraza, Tongeji E.; Ahmed, Wakil; Chira, Chinonyelum; Turner, Erin; Mayaki, Susan; Nandhra, Harpal Singh; Edwards, Tom; Farooq, Saeed
Objective: To describe the pattern of antipsychotic drug prescribing in patients with first episode psychosis, with more emphasis in the use of clozapine in this group of patients. Method: A cross-sectional survey involving six early intervention service (EIS) teams in the West Midlands was conducted. Data was extracted from case notes and electronic records by clinicians working in each participating team. The pattern of antipsychotic prescribing and the changes that took place after being accepted in EIS, including the use of clozapine, was established. Clinicians involved in the treatment of patients in each team rated the overall clinical response to treatment based on the presence or absence of positive psychotic symptoms. Result: 431 patients with FEP were included in the final analysis. Low antipsychotic discontinuation rate was observed, with the majority (88.2%) still being prescribed antipsychotics. Most (77.3%) were prescribed second-generation antipsychotic drugs, with olanzapine (21.8%) and aripiprazole (19.7%) being the most frequently prescribed antipsychotics. There was low rate use of antipsychotic combinations (7.4%), high dose antipsychotic regime (3.9%), low depot antipsychotic prescribing (9.3%), and clozapine use was low (9.7%). On average, three antipsychotics were tried before clozapine was initiated and it took on average 19.5 months from being accepted into EIS to clozapine being initiated. Conclusion: The majority of patients were prescribed antipsychotics within the guidelines. EIS was associated with an overall low antipsychotic discontinuation. There was also a short waiting time before clozapine was initiated following patients being accepted into EIS. PMID:28348730
Paton, C.; Flynn, A.; Shingleton-Smith, A.; McIntyre, S.; Bhaumik, S.; Rasmussen, J.; Hardy, S.; Barnes, T.
Background: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed…
Parks, Joseph; Radke, Alan; Parker, George; Foti, May-Ellen; Eilers, Robert; Diamond, Mary; Svendsen, Dale; Tandon, Rajiv
Findings from 2 pivotal government-funded studies of comparative antipsychotic effectiveness undermine assumptions about the marked superiority of the more expensive second-generation "atypical" medications in comparison to the less expensive first-generation "typical" drugs. Because this assumption was the basis for the almost universal recommendation that these newer antipsychotics be used preferentially resulting in a 10-fold increase in state governmental expenditures on this class of medications over the past decade, a reassessment of policy is called for. To address the issue, the Medical Directors Council of the National Association of State Mental Health Program Directors critically reviewed findings of these studies in the context of other data and considered policy implications in the light of the obligations of state government to make available best possible and individually optimized treatment that is cost-effective. The Medical Directors Council unanimously adopted a set of recommendations to promote appropriate access, efficient utilization, and best practice use. We present our policy statement, in which we provide a succinct background, articulate general principles, and describe a set of 4 broad recommendations. We then summarize our understanding of the current state of knowledge about comparative antipsychotic effectiveness, best antipsychotic practice, and considerations for state policy that represent the basis of our position statement.
Lunsky, Yona; Elserafi, Jonny
Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…
Szczepura, Ala; Owen, David W; Palmer, Thomas; Muhammad, Tariq; Clark, Michael D
Objectives To assess associations between the launch of the National Dementia Strategy (NDS) and antipsychotic prescribing in long-term residential care (LTC) in England. Setting and participants Retrospective analysis of prescribing patterns in 616 LTC institutions (31 619 residents) following launch of the NDS, using information from electronic medicines management system. Primary and secondary outcome measures Antipsychotic prescribing point prevalence (PP) for all residents in a cross section of LTC settings over a 4-year period following NDS launch. Secondary outcomes included dosages, length of treatment and use of recommended second-generation antipsychotics (SGAs) versus first-generation antipsychotics (FGAs). Associations between facility-level PP values and institutional characteristics, resident demographics were explored. Variations across geographical areas examined. Prescription net ingredient costs calculated. Results No statistically significant difference was observed in overall prescribing rates over the 4-year period (Kolmogorov-Smirnov (KS) test p=0.60), and there was no significant shift towards newer SGAs (KS test p=0.32). Dosages were above the maximum indicated in only 1.3% of cases, but duration of prescribing was excessive in 69.7% of cases. Care homes in the highest prescribing quintile were more likely to be located in a deprived area (rate ratio (Q5/Q1) RR=5.89, 95% CI 4.35 to 7.99), registered for dementia (RR=3.38, 95% CI 3.06 to 3.73) and those in the lowest quintile were more likely to be served by a single general practitioner (GP) practice (RR=0.48; 95% CI 0.37 to 0.63); p<0.001 all. A sixfold variation in PP levels was observed between geographical areas. The average annual expenditure on antipsychotics was £65.6 per person resident (2012 prices). Conclusions The NDS in England was not associated with reduced PP levels or the types of antipsychotic prescribing in care homes. Further research is needed to explore why. Clear
Paton, Carol; Bhatti, Sumera; Purandare, Kiran; Roy, Ashok; Barnes, TRE
Objectives To determine the prevalence and quality of antipsychotic prescribing for people with intellectual disability (ID). Design A clinical audit of prescribing practice in the context of a quality improvement programme. Practice standards for audit were derived from relevant, evidence-based guidelines, including NICE. Data were mainly collected from the clinical records, but to determine the clinical rationale for using antipsychotic medication in individual cases, prescribers could also be directly questioned. Settings 54 mental health services in the UK, which were predominantly NHS Trusts. Participants Information on prescribing was collected for 5654 people with ID. Results Almost two-thirds (64%) of the total sample was prescribed antipsychotic medication, of whom almost half (49%) had a schizophrenia spectrum or affective disorder diagnosis, while a further third (36%) exhibited behaviours recognised by NICE as potentially legitimate targets for such treatment such as violence, aggression or self-injury. With respect to screening for potential side effects within the past year, 41% had a documented measure of body weight (range across participating services 18–100%), 32% blood pressure (0–100%) and 37% blood glucose and blood lipids (0–100%). Conclusions These data from mental health services across the UK suggest that antipsychotic medications are not widely used outside of licensed and/or evidence-based indications in people with ID. However, screening for side effects in those patients on continuing antipsychotic medication was inconsistent across the participating services and the possibility that a small number of these services failed to meet basic standards of care cannot be excluded. PMID:27920085
Kaur, Gagandeep; Phillips, Craig L.; Wong, Keith; McLachlan, Andrew J.; Saini, Bandana
Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximise therapeutic effectiveness and minimise/avoid adverse effects. The aim of this study is to investigate the “time of administration” recommendations on chronotherapy for commonly-prescribed medicines in Australia. This study also aimed to explore the quality of information on the timing of administration presented in drug information sources, such as consumer medicine information (CMI) and approved product information (PI). Databases were searched for original research studies reporting on the impact of “time of administration” of the 30 most commonly-prescribed medicines in Australia for 2014. Further, time of administration recommendations from drug information sources were compared to the evidence from chronotherapy trials. Our search revealed 27 research studies, matching the inclusion and exclusion criteria. In 56% (n = 15) of the research studies, the therapeutic effect of the medicine varied with the time of administration, i.e., supported chronotherapy. For some medicines (e.g., simvastatin), circadian-based optimal administration time was evident in the information sources. Overall, dedicated studies on the timing of administration of medicines are sparse, and more studies are required. As it stands, information provision to consumers and health professionals about the optimal “time” to take medications lags behind emerging evidence. PMID:27092523
Nevado-Holgado, Alejo J; Winchester, Laura; Gallacher, John; Lovestone, Simon
0.09 (0.03 to 0.14), breaction time 5 (3 to 6)). Conclusions In this large volunteer study, some commonly prescribed medications were associated with poor cognitive performance. Some associations may reflect underlying diseases for which the medications were prescribed, although the analysis controlled for the possible effect of diagnosis. Other drugs, whose association cannot be linked to the effect of any disease, may need vigilance for their implications in clinical practice. PMID:27903560
Kabbara, Wissam K; Ramadan, Wijdan H; Rahbany, Peggy; Al-Natour, Souhaila
Background Fluoroquinolones are among the most widely prescribed antibiotics. However, concerns about increasing resistant microorganisms and the risk of dysglycemia associated with the use of these agents have emerged. Objective The primary objective of the study was to evaluate the appropriate use of commonly prescribed fluoroquinolones, including appropriate indication, dose, dose adjustment in renal impairment, and duration of treatment. The secondary objective was to investigate the dysglycemic effect of fluoroquinolone use (hypoglycemia and/or hyperglycemia) in diabetic and nondiabetic patients. Methods A prospective observational study at a teaching hospital in Lebanon was conducted over a 6-month period. A total of 118 patients receiving broad-spectrum fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin) were identified. Patients were mainly recruited from internal medicine floors and intensive care units. Results The final percentage for the appropriate indication, dose, and duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A total of 57.1% of the patients did not receive the appropriate dose adjustment according to their level of renal impairment. In addition, dysglycemia occurred in both diabetic and nondiabetic patients. Dysglycemia was more frequently encountered with ciprofloxacin (50.0%), followed by levofloxacin (42.4%) and moxifloxacin (7.6%). Hyperglycemia was more common than hypoglycemia in all groups. The highest incidence of hyperglycemia occurred with levofloxacin (70.0%), followed by ciprofloxacin (39.0%) and moxifloxacin (33.3%). In contrast, hypoglycemia did not occur in the ciprofloxacin group, but it was more common with moxifloxacin (11.1%) and levofloxacin (6.0%). Conclusion The major clinical interventions for the future will adjust the dose and duration of therapy with commonly prescribed fluoroquinolones. The incidence of hypoglycemia was less common than hyperglycemia. PMID:25960658
Welch, R; Chue, P
Recently, antipsychotic medications of the novel or atypical classes have received increased attention because of concerns with respect to potential lengthening of the QT interval, yet the currently available and commonly prescribed conventional antipsychotics are significantly more cardiotoxic, particularly agents in the butyrophenone and phenothiazine classes. Lengthening of the QT interval can be associated with a fatal paroxysmal ventricular arrhythmia known as torsades de pointes. The specific duration of the QT interval at which the risk of an adverse cardiac event is greatest, is not established. There is not only significant variation in the applied definition of an abnormal interval, but the maximal QT interval in healthy volunteers is greater than the currently accepted standards. The QT interval is influenced by normal physiological and pathologic factors, but the mechanisms remain unclear. Using recombinant technology, haloperidol and sertindole have been demonstrated to be high-affinity antagonists of a human cardiac potassium channel encoded by the human ether-a-go-go-related gene. Pimozide, however, has been shown to act principally through calcium channel antagonism, and chlorpromazine may affect sodium channels. Nevertheless, it is possible that these effects are significant only in the presence of predisposing factors, either genetic or acquired. Despite proven efficacy in clinical trials and subsequent supervised use in Europe, a number of recently developed antipsychotic medications are not available to patients in North America. Yet, conventional antipsychotic medications that would not be approved by current safety standards continue to be widely used. PMID:10740988
Fardet, Laurence; Petersen, Irene; Nazareth, Irwin
Background Little is known about the relative risk of common bacterial, viral, fungal, and parasitic infections in the general population of individuals exposed to systemic glucocorticoids, or about the impact of glucocorticoid exposure duration and predisposing factors on this risk. Methods and Findings The hazard ratios of various common infections were assessed in 275,072 adults prescribed glucocorticoids orally for ≥15 d (women: 57.8%, median age: 63 [interquartile range 48–73] y) in comparison to those not prescribed glucocorticoids. For each infection, incidence rate ratios were calculated for five durations of exposure (ranging from 15–30 d to >12 mo), and risk factors were assessed. Data were extracted from The Health Improvement Network (THIN) primary care database. When compared to those with the same underlying disease but not exposed to glucocorticoids, the adjusted hazard ratios for infections with significantly higher risk in the glucocorticoid-exposed population ranged from 2.01 (95% CI 1.83–2.19; p < 0.001) for cutaneous cellulitis to 5.84 (95% CI 5.61–6.08; p < 0.001) for lower respiratory tract infection (LRTI). There was no difference in the risk of scabies, dermatophytosis and varicella. The relative increase in risk was stable over the durations of exposure, except for LRTI and local candidiasis, for which it was much higher during the first weeks of exposure. The risks of infection increased with age and were higher in those with diabetes, in those prescribed higher glucocorticoid doses, and in those with lower plasma albumin level. Most associations were also dependent on the underlying disease. A sensitivity analysis conducted on all individuals except those with asthma or chronic obstructive pulmonary disease produced similar results. Another sensitivity analysis assessing the impact of potential unmeasured confounders such as disease severity or concomitant prescription of chemotherapy suggested that it was unlikely that
... are crucial steps," concluded first author Zhong Wang, Ph.D., also of NIAMS. "Clinicians should consider all factors when choosing which type of blood clot prevention strategy to prescribe for their patients." ...
Cuba, Gabriel Trova; Pignatari, Antonio Carlos Campos; Patekoski, Katya Silva; Luchesi, Lucimila Jorge; Kiffer, Carlos Roberto Veiga
Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: carbapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract
Bole, Cvetka Bačar; Pišlar, Mitja; Šen, Metka; Tavčar, Rok; Mrhar, Aleš
The study aims to identify prescribing and switching patterns of antipsychotics in clinical practice. A 16-month, prospective study was conducted at the Psychiatric Hospital Idrija, Slovenia. Inpatients (N = 311) with schizophrenia spectrum disorders were observed. The causes for switching antipsychotics and switching strategies were analyzed. Analyzing a total of 3954 prescriptions, the collected data confirmed that treatment strategies in this psychiatric hospital are very complex. It was found that 37 percent of inpatients had at least one switch. Moreover, switches that included three or more antipsychotics were detected. The most common causes for switching antipsychotics were adverse reactions and inefficacy or lack of efficacy. Among switching options, abrupt switch was recorded several times. As some patients are receiving several antipsychotics at the same time, it is possible that unusual switching occurs in clinical practice. It seems that the choice of switching strategy is also affected by the cause and urgency for switching an antipsychotic.
Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine. PMID:22587453
Doshi, Jalpa A; Pettit, Amy R; Stoddard, Jeffrey J; Zummo, Jacqueline; Marcus, Steven C
Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice.
Background Several medication classes may contribute to urinary symptoms in older adults. The purpose of this study was to determine the prevalence of use of these medications in a clinical cohort of incontinent patients. Methods A cross-sectional study was conducted among 390 new patients aged 60 years and older seeking care for incontinence in specialized outpatient geriatric incontinence clinics in Quebec, Canada. The use of oral estrogens, alpha-blocking agents, benzodiazepines, antidepressants, antipsychotics, ACE inhibitors, loop diuretics, NSAIDs, narcotics and calcium channel blockers was recorded from each patient’s medication profile. Lower urinary tract symptoms and the severity of incontinence were measured using standardized questionnaires including the International Consultation on Incontinence Questionnaire. The type of incontinence was determined clinically by a physician specialized in incontinence. Co-morbidities were ascertained by self-report. Logistic regression analyses were used to detect factors associated with medication use, as well as relationships between specific medication classes and the type and severity of urinary symptoms. Results The prevalence of medications potentially contributing to lower urinary tract symptoms was 60.5%. Calcium channel blockers (21.8%), benzodiazepines (17.4%), other centrally active agents (16.4%), ACE inhibitors (14.4%) and estrogens (12.8%) were most frequently consumed. Only polypharmacy (OR = 4.9, 95% CI = 3.1-7.9), was associated with medication use contributing to incontinence in analyses adjusted for age, sex, and multimorbidity. No associations were detected between specific medication classes and the type or severity of urinary symptoms in this cohort. Conclusion The prevalence of use of medications potentially causing urinary symptoms is high among incontinent older adults. More research is needed to determine whether de-prescribing these medications results in improved urinary symptoms
McKean, Andrew; Monasterio, Erik
Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.
Piparva, Kiran G.; Buch, J. G.; Chandrani, Kalpesh V.
Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS). However, these drugs have separate set of adverse drug reactions (ADRs). Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex), who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients’ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4–6 mg/day) and olanzepine (at 10–15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2–3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3–9 months) use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized. PMID:22345840
McCall, Catherine; McCall, W Vaughn
Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.
Hsu, Yi-Chien; Chou, Yu-Ching; Chang, Hsin-An; Kao, Yu-Chen; Huang, San-Yuan; Tzeng, Nian-Sheng
Objectives Refractory major depressive disorder (MDD) is a serious problem leading to a heavy economic burden. Antipsychotic augmentation treatment with aripiprazole and quetiapine is approved for MDD patients and can achieve a high remission rate. This study aimed to examine how psychiatrists in Taiwan choose medications and how that choice is influenced by health insurance payments and administrative policy. Design Descriptive study. Outcome measures Eight questions about the choice of treatment strategy and atypical antipsychotics, and the reason to choose aripiprazole. Intervention We designed an augmentation strategy questionnaire for psychiatrists whose patients had a poor response to antidepressants, and handed it out during the annual meeting of the Taiwanese Society of Psychiatry in October 2012. It included eight questions addressing the choice of treatment strategy and atypical antipsychotics, and the reason whether or not to choose aripiprazole as the augmentation antipsychotic. Results Choosing antipsychotic augmentation therapy or switching to other antidepressant strategies for MDD patients with an inadequate response to antidepressants was common with a similar probability (76.1% vs 76.4%). The most frequently used antipsychotics were aripiprazole and quetiapine, however a substantial number of psychiatrists chose olanzapine, risperidone, and sulpiride. The major reason for not choosing aripiprazole was cost (52.1%), followed by insurance official policy audit and deletion in the claims review system (30.1%). Conclusion The prescribing behavior of Taiwanese psychiatrists for augmentation antipsy-chotics is affected by health insurance policy. PMID:25657586
Rhee, YongJoo; Csernansky, John G.; Emanuel, Linda L.; Chang, Chang-Gok; Shega, Joseph W.
Objectives To estimate the proportion of community dwelling older adults with dementia being prescribed a psychotropic and identify patient and caregiver factors associated with antipsychotics use. Methods Retrospective cohort study of The Aging, Demographics, and Memory Study (ADAMS) from 2002 to 2004 designed to assess dementia severity and service use among community-dwelling older adults. The frequency of psychotropic medication (antipsychotics, antidepressants, anticonvulsants and benzodiazepines) use was tabulated and weighted to the US population by dementia diagnosis. Logistic regression analysis identified factors associated with antipsychotic use. Results The 307 participants of ADAMS had the following dementia diagnosis: Alzheimer’s disease (69.29%), vascular dementia (17.74%) and other dementia (12.39%). The proportion of participants prescribed a psychotropic medication broken down by therapeutic class was as 19.07% antipsychotics, 29.08% antidepressants, 9.84% benzodiazepines, and 8.85% anticonvulsants. Older adults with dementia were significantly more likely to receive an antipsychotic if they had moderate dementia (OR =7.4, p<0.05), or severe dementia (OR=5.80, p<0.05), compared to mild dementia or were diagnosed with Alzheimer (OR =6.7, p<0.05) dementia compared to vascular dementia. Older adults with dementia who lived with their caregivers in were significantly less likely to be medicated with antipsychotics (OR= 0.19, p<0.05) compared to those who lived alone. Also, persons with dementia were significantly less likely to be prescribed an antipsychotic if the caregivers were clinically depressed (OR=0.03, p<0.05) compared to those who were not depressed. Conclusion We found psychotropic medication use is common among community-dwelling older adults with dementia. Caregivers appear to have a substantial impact on whether or not an antipsychotic is prescribed, which adds additional complexity to conversations discussing the risk-benefit ratio of
Gellad, WF; Aspinall, SL; Handler, SM; Stone, RA; Castle, N; Semla, TP; Good, CB; Fine, MJ; Dysken, M; Hanlon, JT
Background Antipsychotic medications are commonly prescribed to nursing home residents despite their well-established adverse event profiles. Because little is known about their use in Veterans Administration(VA) nursing homes (i.e., Community Living Centers(CLCs)), we assessed the prevalence and risk factors for their use in older residents of VA CLCs. Methods This cross-sectional study included 3,692 Veterans ≥age 65 who were admitted between January 2004-June 2005 to one of 133 VA CLCs and had a stay of ≥90 days. We used VA Pharmacy Benefits Management data to examine antipsychotic use and VA Medical SAS datasets and the Minimum Data Set to identify evidence-based indications for antipsychotic use (e.g., schizophrenia, dementia with psychosis). We used multivariable logistic regression with generalized estimating equations to identify factors independently associated with antipsychotic use. Results Overall, 948/3,692(25.7%) residents used an antipsychotic, of which 59.3% had an evidence-based indication for use. Residents with aggressive behavior (odds ratio[OR]=2.74, 95% confidence interval[CI]=2.04-3.67) and polypharmacy (9+ drugs; OR=1.84, 95%CI=1.41-2.40) were more likely to receive antipsychotics, as were users of antidepressants (OR=1.37, 95%CI=1.14-1.66), anxiolytic/hypnotics (OR=2.30, 95%CI=1.64-3.23) or drugs for dementia (OR=1.52, 95%CI=1.21-1.92). Those residing in Alzheimer's/dementia special care units were also more likely to use an antipsychotic (OR=1.66, 95%CI=1.26-2.21). Veterans with dementia but no documented psychosis were as likely as those with an evidence-based indication to receive an antipsychotic (OR=1.10, 95%CI=0.82-1.47). Conclusions Antipsychotic use is common in older VA CLC residents, including those without a documented evidence-based indication for use. Further quality improvement efforts are needed to reduce potentially inappropriate antipsychotic prescribing. PMID:23047785
Lencz, Todd; Robinson, Delbert G; Napolitano, Barbara; Sevy, Serge; Kane, John M; Goldman, David; Malhotra, Anil K
Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between -141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone versus olanzapine. Carriers of the deletion allele (n=29) were compared with Ins/Ins homozygotes (noncarriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication. Although deletion carriers were prescribed higher doses of olanzapine (but not risperidone), dose did not seem to account for the genotype effects on weight gain. Given earlier evidence that deletion carriers show reduced symptom response to medication, additional study of appropriate treatment options for these patients seems warranted.
Toteja, Nitin; Gallego, Juan A; Saito, Ema; Gerhard, Tobias; Winterstein, Almut; Olfson, Mark; Correll, Christoph U
Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n = 58 041, range 68-23 183) reported on APP in youth [mean age = 13.4 ± 1.7 yr, 67.1 ± 10.2% male, 77.9 ± 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993-2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9 ± 23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6 ± 24.8). In studies including predominantly children (mean age = <13 yr, N = 5), the most common diagnosis were ADHD (50.6 ± 25.4%) and CD/ODD (39.5 ± 27.5%); while in studies with predominantly adolescents (mean age = ⩾13 yr, N = 7) the most common diagnoses were schizophrenia-spectrum disorders (28.6 ± 23.8%), anxiety disorders (26.9 ± 14.9%) and bipolar-spectrum disorders (26.6 ± 7.0%), followed closely by CD/ODD (25.8 ± 17.7). The prevalence of APP among antipsychotic-treated youth was 9.6 ± 7.2% (5.9 ± 4.5% in child studies, 12.0 ± 7.9% in adolescent studies, p = 0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p = 0.019) and APP involving SGA+SGA combinations (p = 0.0027). No correlation was found with APP definition [⩾1 d (N = 10) vs. >30-⩾90 d (N = 5), p = 0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study.
Nesvåg, Ragnar; Hartz, Ingeborg; Bramness, Jørgen G; Hjellvik, Vidar; Handal, Marte; Skurtveit, Svetlana
Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls.
Lunsky, Yona; Cobigo, Virginie; Wilton, Andrew S.; Somerton, Sarah; Seitz, Dallas P.
Background While up to 45% of individuals with intellectual and developmental disabilities (IDD) have a comorbid psychiatric disorder, and antipsychotics are commonly prescribed, gender differences in the safety of antipsychotics have rarely been studied in this population. Aims To compare men and women with IDD on medical outcomes after antipsychotic initiation. Method Our population-based study in Ontario, Canada, compared 1457 women and 1951 men with IDD newly initiating antipsychotic medication on risk for diabetes mellitus, hypertension, venous thromboembolism, myocardial infarction, stroke and death, with up to 4 years of follow-up. Results Women were older and more medically complex at baseline. Women had higher risks for venous thromboembolism (HR 1.72, 95% CI 1.15–2.59) and death (HR 1.46, 95% CI 1.02–2.10) in crude analyses; but only thromboembolism risk was greater for women after covariate adjustment (aHR 1.58, 95% CI 1.05–2.38). Conclusions Gender should be considered in decision-making around antipsychotic medications for individuals with IDD. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703773
Ansbach, Robert K.; Dybus, Karen; Bergeson, Rachel
Treatment of uncomplicated urinary tract infections (UTIs) has changed in the past few years with researchers advocating empiric treatment for shorter periods of time without the use of cultures. Researchers report that antibiotic resistance of Escherichia coli (E coli) to commonly prescribed antibiotics in uncomplicated UTIs has been increasing.…
Campos Mendes, João; Azeredo-Lopes, Sofia; Cardoso, Graça
This study aimed to establish the prescribing patterns of antipsychotics in acute psychiatric wards across Portugal, to determine the prevalence of polypharmacy and "high-doses" treatment, and to identify possible predictors. Twelve acute psychiatric inpatient units and 272 patients were included. The majority (87.5%) was treated with antipsychotics regardless of diagnosis, and 41.6% had at least two antipsychotics prescribed in combination. Age, use of depot antipsychotics, and antipsychotic "high-doses" were significant predictors of antipsychotic polypharmacy. Excluding 'as required' prescriptions, 13.8% of the patients were prescribed "high-doses" of antipsychotics. When antipsychotics 'as required' prescriptions were considered, 49.2% of the patients were on antipsychotic "high-doses". Age, use of depot antipsychotics, previous psychiatric hospitalization and involuntary admission were significant predictors of antipsychotic "high-doses". These results show that in Portugal the antipsychotics prescribing practices in psychiatric inpatient units diverge from those that are universally recommended, entailing important clinical and economic implications. It seems advisable to optimize the prescription of these drugs, in order to prevent adverse effects and improve the quality of the services provided.
Barrigón, Maria Luisa; Brandt, Sara A; Nitzburg, George C; Ovejero, Santiago; Alvarez-Garcia, Raquel; Carballo, Juan; Walter, Michel; Billot, Romain; Lenca, Philippe; Delgado-Gomez, David; Ropars, Juliette; de la Calle Gonzalez, Ivan; Courtet, Philippe; Baca-García, Enrique
Background Electronic prescribing devices with clinical decision support systems (CDSSs) hold the potential to significantly improve pharmacological treatment management. Objective The aim of our study was to develop a novel Web- and mobile phone–based application to provide a dynamic CDSS by monitoring and analyzing practitioners’ antipsychotic prescription habits and simultaneously linking these data to inpatients’ symptom changes. Methods We recruited 353 psychiatric inpatients whose symptom levels and prescribed medications were inputted into the MEmind application. We standardized all medications in the MEmind database using the Anatomical Therapeutic Chemical (ATC) classification system and the defined daily dose (DDD). For each patient, MEmind calculated an average for the daily dose prescribed for antipsychotics (using the N05A ATC code), prescribed daily dose (PDD), and the PDD to DDD ratio. Results MEmind results found that antipsychotics were used by 61.5% (217/353) of inpatients, with the largest proportion being patients with schizophrenia spectrum disorders (33.4%, 118/353). Of the 217 patients, 137 (63.2%, 137/217) were administered pharmacological monotherapy and 80 (36.8%, 80/217) were administered polytherapy. Antipsychotics were used mostly in schizophrenia spectrum and related psychotic disorders, but they were also prescribed in other nonpsychotic diagnoses. Notably, we observed polypharmacy going against current antipsychotics guidelines. Conclusions MEmind data indicated that antipsychotic polypharmacy and off-label use in inpatient units is commonly practiced. MEmind holds the potential to create a dynamic CDSS that provides real-time tracking of prescription practices and symptom change. Such feedback can help practitioners determine a maximally therapeutic drug treatment while avoiding unproductive overprescription and off-label use. PMID:28126703
Stevenson, David G.; Decker, Sandra L.; Dwyer, Lisa L.; Huskamp, Haiden A.; Grabowski, David C.; Metzger, Eran D.; Mitchell, Susan L.
Objectives To document the extent and appropriateness of use of antipsychotics and benzodiazepines among nursing home residents using a nationally representative survey. Methods Cross-sectional analysis of the 2004 National Nursing Home Survey. Bivariate and multivariate analyses examined relationships between resident and facility characteristics and antipsychotic and benzodiazepine use by appropriateness classification among residents aged 60 years and older (N = 12,090). Resident diagnoses and information about behavioral problems were used to categorize antipsychotic and benzodiazepine use as appropriate, potentially appropriate, or having no appropriate indication. Results More than one quarter (26%) of nursing home residents used an antipsychotic medication, 40% of whom had no appropriate indication for such use. Among the 13% of residents who took benzodiazepines, 42% had no appropriate indication. In adjusted analyses, the odds of residents taking an antipsychotic without an appropriate indication were highest for residents with diagnoses of depression (odds ratio [OR] = 1.31; 95% confidence interval [CI]: 1.12–1.53), dementia (OR = 1.82; 95% CI: 1.52–2.18), and with behavioral symptoms (OR = 1.97, 95% CI: 1.56–2.50). The odds of potentially inappropriate antipsychotic use increased as the percentage of Medicaid residents in a facility increased (OR = 1.08, 95% CI: 1.02–1.15) and decreased as the percentage of Medicare residents increased (OR = 0.46, 95% CI: 0.25–0.83). The odds of taking a benzodiazepine without an appropriate indication were highest among residents who were female (OR = 1.44; 95% CI: 1.18–1.75), white (OR = 1.95; 95% CI: 1.47–2.60), and had behavioral symptoms (OR = 1.69; 95% CI: 1.41–2.01). Conclusion Antipsychotics and benzodiazepines seem to be commonly prescribed to residents lacking an appropriate indication for their use. PMID:20808119
Crossley, Rachel; Withers, Paul
Background: Antipsychotics are the most frequently prescribed psychotropic medication for people with intellectual disabilities. Many people are prescribed this medication for "challenging behaviours" without having had a formal diagnosis of a psychiatric disorder. Antipsychotics have been reported to have severe side-effect profiles, which can…
Aguado, Víctor; Rico, Guillem; Labad, Javier; de Pablo, Joan; Vilella, Elisabet
Background The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes. Objective To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain). Methods A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013. Results The most used antipsychotic was risperidone, identified in 463 (26.3%) patients, followed by olanzapine in 249 (14.1%), paliperidone in 225 (12.7%), zuclopenthixol in 201 (11.4%), quetiapine in 141 (8%), aripiprazole in 100 (5.7%), and clozapine in 100 (5.7%). Almost 8 out of 10 patients (79.3%) were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI) formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6%) were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94–40.97), LAI (OR 9.99, 95% CI 6.45–15.45), psychiatric co-medications (OR 4.25, 95% CI 2.72–6.64), and paliperidone (OR 3.13, 95% CI 1.23–7.92) were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35–0.83) and older age (OR 0.98, 95% CI 0.97–0.99) were related to a low polypharmacy probability. Conclusions Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or
Jeste, Dilip V.; Blazer, Dan; Casey, Daniel; Meeks, Thomas; Salzman, Carl; Schneider, Lon; Tariot, Pierre; Yaffe, Kristine
In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6−1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a ‘black box’ warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is
... Do you prescribe electronically?” For more information about electronic prescribing, call 1-800-MEDICARE (1-800-633- ... TTY users should call 1-877-486-2048 . Electronic eRx Prescribing I went to the pharmacy, and ...
Remick, R A; Fine, S H
The authors examine the clinical problem of which antipsychotic drug to use when antipsychotics are indicated in patients with a seizuire disorder or who are susceptible to seizures. While definitive answers to this problem are still unknown, guidelines are offered for antipsychotic drug use in this situation, based on the author's understanding of psychotropics and epilepsy.
Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark
Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early
Holt, Richard I G; Peveler, Robert C
Hyperprolactinaemia is a common side effect in people receiving antipsychotics. The propensity to cause hyperprolactinaemia differs markedly between antipsychotics as a result of differential dopamine D(2) receptor-binding affinity and ability to cross the blood-brain barrier. Sexual dysfunction is common and under-recognized in people with severe mental illness and is in part caused by hyperprolactinaemia. There are a number of long-term consequences of hyperprolactinaemia, including osteoporosis. Regular monitoring before and during treatment will help identify those developing antipsychotic-induced hyperprolactinaemia. The treatment includes dose reduction and change in antipsychotic. Where this is not possible because of the risk of relapse of the mental illness, sex steroid replacement may be helpful in improving symptoms secondary to hypogonadism and reducing the risk of osteoporosis. Tertiary prevention of complications should also be considered.
Akam, Elizabeth; Strange, Philip G
Mechanisms of action of several atypical antipsychotic drugs have been examined at the D(2) dopamine receptor expressed in CHO cells. The drugs tested were found to exhibit inverse agonist activity at the D(2) dopamine receptor based on their effects to potentiate forskolin-stimulated cyclic AMP (cAMP) accumulation. Each of the antipsychotic drugs tested (clozapine, olanzapine, quetiapine and risperidone) increased cAMP accumulation to the same extent. The increase in cAMP was also similar to that seen with typical antipsychotic drugs. Inverse agonism at the D(2) dopamine receptor seems, therefore, to be a property common to all classes of antipsychotic drugs. The effect of sodium ions on the binding of the drugs to the receptor was also assessed. Each of the atypical antipsychotic drugs tested here bound with higher affinity in the absence of sodium ions. Previous studies have shown that some antipsychotic drugs are insensitive to sodium ions and some bind with higher affinity in the presence of sodium ions. Given that all of these antipsychotic drugs are inverse agonists, it may be concluded that this sodium ion sensitivity is unrelated to mechanisms of inverse agonism.
DelBello, Melissa; Grcevich, Stephen
Children and adolescents commonly present to clinical settings with more severe psychopathology than previously recognized. Physicians evaluating children may be confronted with clinical manifestations of early-onset schizophrenia, including command hallucinations and delusional thinking, severe irritability and suicidality associated with juvenile-onset bipolar disorder, or the severe aggression of a child with a pervasive developmental disorder. In these as well as other clinical situations, the potential risks and benefits of treatment with atypical antipsychotics should be considered. In this article, we summarize the clinical manifestations of psychiatric disorders in children and adolescents, with particular attention to the disorders for which the benefits of prescribing an atypical antipsychotic may outweigh the potential risks. We also describe the differences in the clinical presentation of these disorders between youth and adults.
Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary
Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.
Wilson, Robin; Jackson, Richard; Ball, Michael; Shetty, Hitesh; Broadbent, Matthew; Stewart, Robert; McGuire, Philip; Bhattacharyya, Sagnik
Objective To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP). Design Observational study with exploratory mediation analysis. Setting Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust. Participants 2026 people presenting to early intervention services with FEP. Exposure Cannabis use at presentation, identified using natural language processing. Main outcome measures admission to psychiatric hospital and clozapine prescription up to 5 years following presentation. Mediator Number of unique antipsychotics prescribed. Results Cannabis use was present in 46.3% of the sample at first presentation and was particularly common in patients who were 16–25, male and single. It was associated with increased frequency of hospital admission (incidence rate ratio 1.50, 95% CI 1.25 to 1.80), increased likelihood of compulsory admission (OR 1.55, 1.16 to 2.08) and greater number of days spent in hospital (β coefficient 35.1 days, 12.1 to 58.1). The number of unique antipsychotics prescribed, mediated increased frequency of hospital admission (natural indirect effect 1.09, 95% CI 1.01 to 1.18; total effect 1.50, 1.21 to 1.87), increased likelihood of compulsory admission (natural indirect effect (NIE) 1.27, 1.03 to 1.58; total effect (TE) 1.76, 0.81 to 3.84) and greater number of days spent in hospital (NIE 17.9, 2.4 to 33.4; TE 34.8, 11.6 to 58.1). Conclusions Cannabis use in patients with FEP was associated with an increased likelihood of hospital admission. This was linked to the prescription of several different antipsychotic drugs, indicating clinical judgement of antipsychotic treatment failure. Together, this suggests that cannabis use might be
Fretwell, Christine; Felce, David
Background: Anti-psychotic medications are widely prescribed to people with intellectual disabilities and have a range of negative side effects. The aim was to identify the level of knowledge of anti-psychotic medications and their side effects among key carers or home managers of adults with intellectual disabilities living in residential group…
Connolly, Anne; Taylor, David
Background: Black people are over represented in mental health services and prescribing of antipsychotics differs by race in some countries. Our previous UK research into the prescribing of antipsychotics in large, multicentre studies found no important differences for black and white patients. However, we received several comments challenging our findings. We wanted to test the validity of these anecdotes by devising two case vignettes that differed only by race and asking prescribers to choose antipsychotic treatment. Method: A case study was sent to all medical prescribers in the South London and Maudsley NHS Trust. Half of the prescribers for each grade of staff were sent the case study where the ethnicity of the patient was white and the other half where the ethnicity was black. Participants were asked to describe what they would prescribe for the patient. Outcomes were total percentage maximum dose, high dose, type of antipsychotic, route of administration and antipsychotic polypharmacy. Results: We received 123 completed case studies and demographic data forms from prescribers. There were no differences in percentage maximum dose, high dose, type, route and number of antipsychotics prescribed by case study ethnicity. Conclusions: Prescribing for UK black and white patients is broadly similar when tested in clinical and theoretical studies. PMID:27354905
Matson, Johnny L.; Mahan, Sara
Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…
Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J
Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.
Lencz, Todd; Robinson, Delbert G.; Napolitano, Barbara; Sevy, Serge; Kane, John M.; Goldman, David; Malhotra, Anil K.
Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between −141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone (RIS) vs. olanzapine (OLZ). Carriers of the deletion allele (n=29) were compared to Ins/Ins homozygotes (non-carriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers demonstrated significantly more weight gain after 6 weeks of treatment regardless of assigned medication. While deletion carriers were prescribed higher doses of OLZ (but not RIS), dose did not appear to account for the genotype effects on weight gain. Given previous evidence that deletion carriers demonstrate reduced symptom response to medication, additional study of appropriate treatment options for these patients appears warranted. PMID:20664489
Chandra, Nilanjan C.; Sheth, Shabina A.; Mehta, Ritambhara Y.; Dave, Kamlesh R.
Tardive dystonia (TD) is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics. PMID:28250568
Lee, Philip E; Gill, Sudeep S; Rochon, Paula
Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient. PMID:19412500
Antipsychotic drugs are licensed as treatment for schizophrenia and other mental health disorders but can cause a range of unwanted effects that require close monitoring by, and close collaboration between, healthcare professionals across a range of settings. This applies to both first-generation and second-generation antipsychotics (FGAs and SGAs; sometimes known as conventional and atypical antipsychotics, respectively). Here we discuss monitoring for unwanted effects of antipsychotics in adults, with a particular focus on SGAs.
Kruse, Amanda Brinch; de Knegt, Leonardo Víctor; Nielsen, Liza Rosenbaum; Alban, Lis
It is often stated that vaccines may help reduce antimicrobial use in swine production. However, limited evidence is available outside clinical trials. We studied the change in amounts of antimicrobials prescribed for weaners and finishers in herds following initiation of vaccination against five common endemic infections: Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, porcine circovirus type II, porcine reproductive and respiratory syndrome virus, and Lawsonia intracellularis. Comparison was made to the change after a randomly selected date in herds not vaccinating against each of the infections. Danish sow herds initiating vaccination during 2007–2013 were included (69–334 herds, depending on the analysis). Danish sow herds with no use of the vaccine in question were included as non-exposed herds (130–570 herds, depending on the analysis). Antimicrobial prescriptions for weaners in sow herds and for finishers in receiving herds were extracted from the VetStat database for a period of 12 months before and 6–18 months after the first purchase of vaccine, or random date and quantified as average animal daily doses (ADDs) per 100 animals per day. The herd-level difference between ADD in the period after and before vaccination was the outcome in linear regression models for weaner pigs, and linear mixed-effects models for finishing pigs, taking into account sow herds delivering pigs to two or more finisher herds. Three plausible risk factors (Baseline ADD, purchase of specific vaccine, purchase of other vaccines) and five confounders (herd size, export and herd health status, year and season) were initially considered in all 10 models. The main significant effect in all models was the Baseline ADD; the higher the Baseline ADD was for weaner and finishing pigs, the larger the decrease in ADD was following vaccination (or random date for non-vaccinating herds). Regardless of vaccination status, almost equal proportions of herds experienced a
Velligan, Dawn I.; Lam, Yui-Wing Francis; Glahn, David C.; Barrett, Jennifer A.; Maples, Natalie J.; Ereshefsky, Larry; Miller, Alexander L.
The definition and assessment of adherence vary considerably across studies. Increasing consensus regarding these issues is necessary to improve our understanding of adherence and the development of more effective treatments. We review the adherence literature over the past 3 decades to explore the definitions and assessment of adherence to oral antipsychotics in schizophrenia patients. A total of 161 articles were identified through MEDLINE and PsycINFO searches. The most common method used to assess adherence was the report of the patient. Subjective and indirect methods including self-report, provider report, significant other report, and chart review were the only methods used to assess adherence in over 77% (124/161) of studies reviewed. Direct or objective measures including pill count, blood or urine analysis, electronic monitoring, and electronic refill records were used in less than 23% (37/161) of studies. Even in studies utilizing the same methodology to assess adherence, definitions of an adherent subject varied broadly from agreeing to take any medication to taking at least 90% of medication as prescribed. We make suggestions for consensus development, including the use of recommended terminology for different subject samples, the increased use of objective or direct measures, and the inclusion in all studies of an estimate of the percentage of medication taken as prescribed in an effort to increase comparability among studies. The suggestions are designed to advance the field with respect to both understanding predictors of adherence and developing interventions to improve adherence to oral antipsychotic medications. PMID:16707778
Collin, Julius; Jonasdottir Bergman, Gudrun; Borg, Natalia; Salmi, Peter; Fastbom, Johan
Aim The aim of the study was to examine mortality risk associated with use of antidepressants and antipsychotics classified with torsades de pointes (TdP) risk in elderly. Methods A matched case–control register study was conducted in people 65 years and older dying outside hospital from 2008–2013 (n = 286 092) and matched controls (n = 1 430 460). The association between prescription of antidepressants and antipsychotics with various TdP risk according to CredibleMeds (www.crediblemeds.org) and all‐cause mortality was studied by multivariate conditional logistic regression adjusted for comorbidity and several other confounders. Results Use of antidepressants classified with known or possible TdP risk, was associated with higher adjusted risk for mortality (OR 1.53, 95% CI 1.51, 1.56 and OR 1.63, 95% CI 1.61, 1.67, respectively) compared with antidepressants classified with conditional TdP risk (OR 1.25, 95% CI 1.22, 1.28) or without TdP classification (OR 0.99, 95% CI 0.94, 1.05). Antipsychotics classified with known TdP risk were associated with higher risk (OR 4.57, 95% CI 4.37, 4.78) than antipsychotics with possible risk (OR 2.58, 95% CI 2.52, 2.64) or without TdP classification (OR 2.14, 95% CI 2.03, 2.65). The following risk ranking was observed for commonly used antidepressants: mirtazapine > citalopram > sertraline > amitriptyline and for antipsychotics: haloperidol > risperidone >olanzapine > quetiapine. Conclusion The CredibleMeds system predicted drug‐associated risk for mortality in the elderly at the risk class level. Among antipsychotics, haloperidol, and among antidepressants, mirtazapine and citalopram, were associated with the highest risks. The results suggest that the TdP risk with antidepressants and antipsychotics should be taken into consideration when prescribing to the elderly. PMID:26574175
Yin, John; Barr, Alasdair M; Ramos-Miguel, Alfredo; Procyshyn, Ric M
Chronic prescription of antipsychotics seems to lose its therapeutic benefits in the prevention of recurring psychotic symptoms. In many instances, the occurrence of relapse from initial remission is followed by an increase in dose of the prescribed antipsychotic. The current understanding of why this occurs is still in its infancy, but a controversial idea that has regained attention recently is the notion of iatrogenic dopamine supersensitivity. Studies on cell cultures and animal models have shown that long-term antipsychotic use is linked to both an upregulation of dopamine D2-receptors in the striatum and the emergence of enhanced receptor affinity to endogenous dopamine. These findings have been hypothesized to contribute to the phenomenon known as dopamine supersensitivity psychosis (DSP), which has been clinically typified as the foundation of rebound psychosis, drug tolerance, and tardive dyskinesia. The focus of this review is the update of evidence behind the classification of antipsychotic induced DSP and an investigation of its relationship to treatment resistance. Since antipsychotics are the foundation of illness management, a greater understanding of DSP and its prevention may greatly affect patient outcomes.
Avasthi, Ajit; Aggarwal, Munish; Grover, Sandeep; Khan, Mohd Khalid Rasheed
Antipsychotic as a class of medications became available for treatment of various psychiatric disorders in the early 1950’s. Over the last 60 years many antipsychotics have become available. In line with the west, Indian researchers have evaluated the efficacy of antipsychotics in various conditions. Additionally, researchers have also evaluated the important safety and tolerability issues. Here, we review data originating from India in the form of drug trials, effectiveness, usefulness, safety and tolerability of antipsychotics. Additionally, data with respect to other important treatment related issues is discussed. PMID:21836703
Routledge, Philip A
The challenge to achieve safe prescribing merits the adjective 'titanic'. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the 'Seven C's'. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm.
Kroken, Rune A; Johnsen, Erik; Ruud, Torleif; Wentzel-Larsen, Tore; Jørgensen, Hugo A
Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also
Parikh, Tapan; Goyal, Dharmendra; Scarff, Jonathan R; Lippmann, Steven
Antipsychotic drugs prescribed to treat psychiatric symptoms during the postpartum period are secreted into breast milk. Because breast-feeding is crucial to infant development, it is important to select a medication that poses the fewest adverse consequences. Aripiprazole, haloperidol, perphenazine, and trifluoperazine demonstrate no known developmental dangers. Olanzapine, quetiapine, and risperidone are cited as safe, although monitoring is recommended. Chlorpromazine and clozapine may induce developmental concerns. There are limited safety data for asenapine, fluphenazine, iloperidone, loxapine, lurasidone, paliperidone, pimozide, thioridazine, thiothixene, and ziprasidone. Clinicians should choose medications considered to be the safest and prescribe them at the lowest effective doses.
Pich, Emilio Merlo; Vargas, Gabriel; Domenici, Enrico
Molecular biomarkers for antipsychotic treatments have been conceptually linked to the measurements of dopamine functions, mostly D(2) receptor occupancy, either by imaging using selective PET/SPECT radioactive tracers or by assessing plasma prolactin levels. A quest for novel biomarkers was recently proposed by various academic, health service, and industrial institutions driven by the need for better treatments of psychoses. In this review we conceptualize biomarkers within the Translational Medicine paradigm whose goal was to provide support to critical decision-making in drug discovery. At first we focused on biomarkers as outcome measure of clinical studies by searching into the database clinicaltrial.gov. The results were somewhat disappointing, showing that out of 1,659 antipsychotic trials only 18 used a biomarker as an outcome measure. Several of these trials targeted plasma lipids as sentinel marker for metabolic adverse effects associated with the use of atypical antipsychotics, while only few studies were aimed to new disease specific biological markers. As an example of a mechanistic biomarker, we described the work done to progress the novel class of glycine transporter inhibitors as putative treatment for negative symptoms of schizophrenia. We also review how large-scale multiplex biological assays were applied to samples from tissues of psychiatric patients, so to learn from changes of numerous analytes (metabolic products, lipids, proteins, RNA transcripts) about the substrates involved in the disease. We concluded that a stringent implementation of these techniques could contribute to the endophenotypic characterization of patients, helping in the identification of key biomarkers to drive personalized medicine and new treatment development.
Downer, Frances; Shepherd, Chew Kim
Nurse prescribing has been established in the UK since 1994, however, limited focus has been placed on the experiences of district nurses adopting this additional role. This phenomenological study explores the experiences of district nurses prescribing as nurse independent prescribers across the West of Scotland. A qualitative Heideggarian approach examined the every-day experiences of independent prescribing among district nurses. A purposive sample was used and data collected using audio taped one-to-one informal interviews. The data was analysed thematically using Colaizzi's seven procedural steps. Overall these nurses reported that nurse prescribing was a predominantly positive experience. Participants identified improvements in patient care, job satisfaction, level of autonomy and role development. However, some of the participants indicated that issues such as support, record keeping, confidence and ongoing education are all major influences on prescribing practices.
Park, Seon-Cheol; Lee, Myung-Soo; Kang, Seung-Gul; Lee, Seung-Hwan
This study aimed to analyze the patterns of antipsychotic prescription to patients with schizophrenia in Korea. Using the Health Insurance Review & Assessment Service-National Patients Sample (HIRA-NPS), which was a stratified sampling from the entire population under the Korean national health security system (2009), descriptive statistics for the patterns of the monopharmacy and polypharmacy, neuropsychiatric co-medications, and prescribed individual antipsychotic for patients with schizophrenia were performed. Comparisons of socioeconomic and clinical factors were performed among patients prescribed only with first- and second-generation antipsychotics. Of 126,961 patients with schizophrenia (age 18-80 yr), 13,369 were prescribed with antipsychotic monopharmacy and the rest 113,592 with polypharmacy. Two or more antipsychotics were prescribed to 31.34% of the patients. Antiparkinson medications (66.60%), anxiolytics (65.42%), mood stabilizers (36.74%), and antidepressants (25.90%) were co-medicated. Patients who were prescribed only with first-generation antipsychotics (n=26,254) were characterized by significantly older age, greater proportion of male, higher proportion of medicaid, higher total medical cost, lower self-payment cost, and higher co-medication rates of antiparkinson agents and anxiolytics than those who were prescribed only with second-generation antipsychotics (n=67,361). In this study, it has been reported substantial prescription rates of first-generation antipsychotics and antipsychotic polypharmacy and relatively small prescription rate of clozapine to patients with schizophrenia. Since this study has firstly presented the patterns of antipsychotic prescription to schizophrenic patients in Korean national population, the findings of this study can be compared with those of later investigations about this theme.
Background Antipsychotic are the cornerstone in the treatment of schizophrenia. They also have a number of side-effects. Constipation is thought to be common, and a potential serious side-effect, which has received little attention in recent literature. Method We performed a retrospective study in consecutively admitted patients, between 2007 and 2009 and treated with antipsychotic medication, linking different electronic patient data to evaluate the prevalence and severity of constipation in patients with schizophrenia under routine treatment conditions. Results Over a period of 22 months 36.3% of patients (99) received at least once a pharmacological treatment for constipation. On average medication for constipation was prescribed for 273 days. Severe cases (N = 50), non-responsive to initial treatment, got a plain x-ray of the abdomen. In 68.4% fecal impaction was found. Conclusion A high prevalence of constipation, often severe and needing medical interventions, was confirmed during the study period. Early detection, monitoring over treatment and early intervention of constipation could prevent serious consequences such as ileus. PMID:21385443
Singh, Sourabh Moti; Haddad, Peter M.; Husain, Nusrat; Heaney, Eamonn; Tomenson, Barbara; Chaudhry, Imran B.
Objectives: The objective of this study was to compare patients’ attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). Method: A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. Results: The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. Conclusions: Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including
Gallego, Juan A.; Nielsen, Jimmi; De Hert, Marc; Kane, John M.; Correll, Christoph U.
Introduction Antipsychotic polypharmacy (APP), the concomitant use of ≥2antipsychotics, is common in clinical practice. Prior reviews have focused on the efficacy of APP, but no systematic review exists regarding the safety and tolerability of this practice. Areas covered in this review We conducted a systematic review of adverse effects associated with APP. Case series with ≥2 patients, chart reviews, naturalistic, data base, cohort and randomized studies that reported on the association between APP in general or specific APP combinations and global or specific adverse effect were included. We discuss methodological limitations of available studies and provide recommendations for clinicians and future research. Expert Opinion Across mostly small and uncontrolled studies, APP has been associated with increased global side effect burden, rates of Parkinsonian side effects, anticholinergic use, hyperprolactinemia, sexual dysfunction, hypersalivation, sedation/somnolence, cognitive impairment, and diabetes. Effects on akathisia and mortality were inconclusive. Although some combinations, particularly aripiprazole augmentation of an agent with greater side effect burden, may reduce weight gain, dyslipidemia, hyperprolactinemia and sexual dysfunction, APP should remain a last resort treatment option after monotherapy, switching and non-antipsychotic combinations have failed. More and high quality data are needed to further inform the individualized risk-benefit evaluation of APP. PMID:22563628
Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.
Background: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs.…
Antipsychotic medications are important for the successful management of schizophrenia. Continuous treatment with medication is superior in relapse prevention and non-adherence to antipsychotic medication is associated with a poor clinical outcome. Long-acting injectable antipsychotics (LAIs) that can guarantee adherence to a treatment regimen could be a useful treatment option. With the introduction of second-generation atypical antipsychotics-long acting injection (SGA-LAI), the risks for extrapyramidal adverse events are decreased. The indications for SGA-LAI have been extended from chronic, stabilized patients to acute psychotic patients. Some studies investigated the use of LAI in first-episode schizophrenia patients and raised the possibility of prescribing LAI as a treatment option. However, there is still limited research using LAI in first-episode schizophrenia. More well-designed, randomized, controlled clinical trials using SGA-LAIs in first episode schizophrenia are needed. Additionally, studies on side effects of SGA-LAI in long-term use are required prior to recommending LAI for patients with first episode schizophrenia. PMID:23678347
Samalin, Ludovic; Charpeaud, Thomas; Blanc, Olivier; Heres, Stephan; Llorca, Pierre-Michel
Depot formulations are not widely used in everyday practice. This study aimed to assess psychiatrists' attitudes toward the use of long-acting injectable (LAI) antipsychotics in schizophrenia. We interviewed 113 French psychiatrists about the factors that influenced their prescription of LAI antipsychotics. Multidimensional and cluster analyses were used to detect correlations. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk for extrapyramidal symptoms; and for second-generation LAI, it is the unavailability of the equivalent oral formulation. Four factors incite the psychiatrists to prescribe LAI. Two different clusters of patients can also be identified. Most factors influencing the clinicians' attitudes toward the use of LAI antipsychotics are shared in many countries. Conversely, some attitudes related to organizational aspects, particularly the relevance of health care costs, may vary from one country to another.
Routledge, Philip A
The challenge to achieve safe prescribing merits the adjective ‘titanic’. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the ‘Seven C's’. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396
Samalin, Ludovic; Garnier, Marion; Auclair, Candy; Llorca, Pierre-Michel
The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia. PMID:27869767
Samalin, Ludovic; Garnier, Marion; Auclair, Candy; Llorca, Pierre-Michel
The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians' decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.
ERSAN, Etem Erdal; YILDIZ, Mustafa
Introduction The aim of this survey is to determine the pattern of antipsychotic drug use in patients with psychotic disorders, living in board and care facilities and to investigate the related factors. Methods We evaluated the antipsychotic drug use pattern in outpatients with psychotic disorders according to DSM-IV, living in board and care facilities. Patients using polypharmacy at least one month were compared with patients using monotherapy in terms of clinical and demographic characteristics. Results Antipsychotic polypharmacy (with two: 34%, with more than two: 28%) was identified in 62% of the patients. The most frequently prescribed combination was olanzapine+quetiapine (13%), the rate of first and second generation combination was 50%, the rate of second generation antipsychotic combination was 44%, and the rate of first generation anytipsychotic combination was 4% in the two antipsychotic drug combination group. The rate of clozapine use was 3%. Use of polypharmacy was associated with the diagnosis of schizophrenia and schizoaffective disorder, young age, suicidal behavior, multiple hospitalizations, clinical severity, and the need of anticholinergic drug. Conclusion The ratio of using more than two antipsychotic drug combination is high (28%) in psychotic patients living in board and care, and rate of clozapine use is low, which shows that clinical practice is inconsistent with the treatment guidelines recommendations. It appears that further education to rationale antipsychotic drug use in psychiatric practices is required.
Dibben, Claire R M; Khandaker, Golam M; Underwood, Benjamin R; O'Loughlin, Christopher; Keep, Catherine; Mann, Louisa; Jones, Peter B
Aims and method To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication. Results Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have more or 'stronger' side-effects. Lack of training experience was noted as the second leading concern for prescribing FGAs. A quarter of trainees received no training exposure to the older drugs and two-thirds had never initiated these drugs themselves. Although nearly 90% of trainees felt confident about initiating an oral SGA as a regular medication, only about 40% felt confident with FGAs (P<0.001). Clinical implications The survey highlights worrying gaps in training. FGAs can be used effectively, minimising side-effects, by careful dose titration, avoiding antipsychotic polypharmacy, high-dose, and high-potency drugs, thus ensuring they are not lost to future generations of psychiatrists.
Dibben, Claire R. M.; Khandaker, Golam M.; Underwood, Benjamin R.; O'Loughlin, Christopher; Keep, Catherine; Mann, Louisa; Jones, Peter B.
Aims and method To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication. Results Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have more or ‘stronger’ side-effects. Lack of training experience was noted as the second leading concern for prescribing FGAs. A quarter of trainees received no training exposure to the older drugs and two-thirds had never initiated these drugs themselves. Although nearly 90% of trainees felt confident about initiating an oral SGA as a regular medication, only about 40% felt confident with FGAs (P<0.001). Clinical implications The survey highlights worrying gaps in training. FGAs can be used effectively, minimising side-effects, by careful dose titration, avoiding antipsychotic polypharmacy, high-dose, and high-potency drugs, thus ensuring they are not lost to future generations of psychiatrists. PMID:27087995
Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E
Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications
Donohue, Julie M.; Normand, Sharon-Lise T.; Horvitz-Lennon, Marcela; Men, Aiju; Berndt, Ernst R.; Huskamp, Haiden A.
Background Regional variation in US Medicare prescription drug spending is driven by higher prescribing of costly brand-name drugs in some regions. This variation likely arises from differences in the speed of diffusion of newly-approved medications. Second-generation antipsychotics were widely adopted for treatment of severe mental illness and for several off-label uses. Rapid diffusion of new psychiatric drugs likely increases drug spending but its relationship to non-drug spending is unclear. The impact of antipsychotic diffusion on drug and medical spending is of great interest to public payers like Medicare, which finance a majority of mental health spending in the U.S. Aims We examine the association between physician adoption of new antipsychotics and antipsychotic spending and non-drug medical spending among disabled and elderly Medicare enrollees. Methods We linked physician-level data on antipsychotic prescribing from an all-payer dataset (IMS Health's Xponent™) to patient-level data from Medicare. Our physician sample included 16,932 U.S. psychiatrists and primary care providers with ≥10 antipsychotic prescriptions per year from 1997-2011. We constructed a measure of physician adoption of 3 antipsychotics introduced during this period (quetiapine, ziprasidone and aripiprazole) by estimating a shared frailty model of the time to first prescription for each drug. We then assigned physicians to one of 306 U.S. hospital referral regions (HRRs) and measured the average propensity to adopt per region. Using 2010 data for a random sample of 1.6 million Medicare beneficiaries, we identified 138,680 antipsychotic users. A generalized linear model with gamma distribution and log link was used to estimate the effect of region-level adoption propensity on beneficiary-level antipsychotic spending and non-drug medical spending adjusting for patient demographic and socioeconomic characteristics, health status, eligibility category, and whether the antipsychotic was
Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics
Bernardo, Miguel; San, Luis; Olivares, José M; Dilla, Tatiana; Polavieja, Pepa; Gilaberte, Inmaculada; Álvarez, María; Ciudad, Antonio
Purpose To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. Patients and methods A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist’s clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Results Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was €1,407 (€897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. Conclusion LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of
Switching antipsychotics is more and more common in our clinical practice. Several reasons can explain this observation. We have more and more antipsychotics available on the market with different receptor binding profiles and also different tolerability issues. Usually, the reasons of the switch are the following: insufficient efficacy or problems of tolerance (weight gain, metabolic disorders, extrapyramidal symptoms, hyperprolactinemia, sedation, sexual dysfunction). So that the switch takes place without complications, it is essential for the clinician to have full knowledge of both the receptor binding profiles of the antipsychotics in question and their half-life. The clinician has to expect a dopaminergic rebound when the introduced antipsychotic has a lesser affinity for the dopaminergic D2 receptor than that which is withdrawn or if it is a partial agonist with a particularly long half-life. On the other hand, a histaminergic or cholinergic rebound can be expected if the new antipsychotic has a lesser affinity for these two receptors. In all these scenarios, a "plateau" switch will often be recommended. Now, if a faster switch is imperative, various medication strategies exist to try to decrease the impact of the rebound effects.
The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987
Lind, Cpt Christopher K; Carchedi, Cpt Lisa R; Staudenmeier, Ltc James J; Diebold, Ltc P Carroll J
The atypical antipsychotics have been touted by many as having minimal extrapyramidal symptoms. This case series from the Tripler Army Medical Center Psychiatry Graduate Medical Education Program presents the extrapyramidal symptoms observed with four different atypical antipsychotic medications. Also reviewed are the mechanisms of action that atypical antipsychotics and first-generation antipsychotics use to treat the symptoms of schizophrenia. Cases reviewed include a schizophrenic male patient whose dose of risperidone was doubled from 6mg to 12mg overnight and developed an acute dystonic reaction; a young male patient with a substance-induced psychosis who unintentionally doubled his ziprasidone dose in 24 hours, resulting in an acute dystonic reaction; a young female patient on paroxetine who also recently started olanzapine and had complaints consistent with akathisia that resolved with treatment; and an adolescent female patient on escitalopram for obsessive-compulsive disorder who after starting aripiprazole developed Parkinsonism. All four cases illustrate that even though atypical antipsychotics are less likely to cause extrapyramidal symptoms than their first generation cousins, the physician should be aware that these symptoms may still occur and need to be treated.
Carchedi, CPT. Lisa R.; Staudenmeier, LTC. James J.; Diebold, LTC(P). Carroll J.
The atypical antipsychotics have been touted by many as having minimal extrapyramidal symptoms. This case series from the Tripler Army Medical Center Psychiatry Graduate Medical Education Program presents the extrapyramidal symptoms observed with four different atypical antipsychotic medications. Also reviewed are the mechanisms of action that atypical antipsychotics and first-generation antipsychotics use to treat the symptoms of schizophrenia. Cases reviewed include a schizophrenic male patient whose dose of risperidone was doubled from 6mg to 12mg overnight and developed an acute dystonic reaction; a young male patient with a substance-induced psychosis who unintentionally doubled his ziprasidone dose in 24 hours, resulting in an acute dystonic reaction; a young female patient on paroxetine who also recently started olanzapine and had complaints consistent with akathisia that resolved with treatment; and an adolescent female patient on escitalopram for obsessive-compulsive disorder who after starting aripiprazole developed Parkinsonism. All four cases illustrate that even though atypical antipsychotics are less likely to cause extrapyramidal symptoms than their first generation cousins, the physician should be aware that these symptoms may still occur and need to be treated. PMID:21152153
Katare, Yogesh K; Piazza, Justin E; Bhandari, Jayant; Daya, Ritesh P; Akilan, Kosalan; Simpson, Madeline J; Hoare, Todd; Mishra, Ram K
Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods.
LEE, JIN-KU; NAM, DO-HYUN; LEE, JEONGWU
Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed. PMID:26893731
Klein, Lauren; Bangh, Stacey; Cole, Jon B.
Introduction Case reports and poison center data have demonstrated that the second-generation antipsychotic quetiapine is being obtained and used for recreational abuse. The purpose of this study was to describe the relative rates of single-substance abuse for different atypical antipsychotics and compare their demographic and clinical features. Methods We conducted a 10-year retrospective analysis of the National Poison Data System (NPDS) database (2003 – 2013). Trained nurses and pharmacists with specialty training in toxicology prospectively collect all NPDS data at poison control centers around the United States. We queried the NPDS for all cases of single-substance second-generation antipsychotic exposures coded as “intentional abuse.” The data provided by the NPDS regarding rates and clinical features of quetiapine abuse and the abuse of all other second-generation antipsychotics were compared and described descriptively. Results During the study period, 2,118 cases of quetiapine abuse and 1,379 cases of other second-generation antipsychotic abuse were identified. Quetiapine abuse was more common than the abuse of other second-generation antipsychotics, compromising 60.6% of all abuse cases during the study period. After quetiapine, the next most frequently abused medications were risperidone (530 cases, 15.2%) and olanzapine (246 cases, 7.0%). For all second-generation antipsychotics including quetiapine, central nervous system clinical effects were most common, including drowsiness, confusion, and agitation. Other serious clinical effects observed with second-generation antipsychotic abuse included hypotension, respiratory depression, and seizures. Conclusion Quetiapine abuse is relatively common, and is abused far more often than any other second-generation antipsychotic. Emergency physicians should be aware of the clinical effects that may occur after second-generation antipsychotic abuse. PMID:28210359
Beaton, Albert E., Jr.
Commonality analysis is an attempt to understand the relative predictive power of the regressor variables, both individually and in combination. The squared multiple correlation is broken up into elements assigned to each individual regressor and to each possible combination of regressors. The elements have the property that the appropriate sums…
Noggle, Chad A.; Dean, Raymond S.
The use of antipsychotic medications within the school-age population is rapidly increasing. Although typical antipsychotics may be used in rare cases, this influx is largely secondary to the availability of the atypical antipsychotics. Reduction of possible adverse effects and increased efficacy represent the primary basis for the atypical…
Hu, Kai-Fang; Chou, Yu-Hsiang; Wen, Yen-Hsia; Hsieh, Kun-Pin; Tsai, Jui-Hsiu; Yang, Pinchen; Yang, Yi-Hsin; Lin, Chun-Hung Richard
We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients.
Marques, Tiago Reis; Levine, Stephen Z; Reichenberg, Avi; Kahn, Rene; Derks, Eske M; Fleischhacker, Wolfgang W; Rabinowitz, Jonathan; Kapur, Shitij
The clinical expression of schizophrenia is generally reported to be expressed by three to five different factors (i.e. positive, negative, disorganization, excitability, anxiety-depression symptoms). It is often claimed that antipsychotic medications are particularly helpful for positive symptoms, but not for the others, suggesting a differential efficacy for different aspects of the disorder. We formally tested this claim. Using Structural Equation Modeling in two large [1884 patients] clinical trials in schizophrenia, we compared the model of a common general effect of antipsychotics to models whereby the antipsychotics have multiple and differential effects on the different factors of the illness. We validated the generalizability of the model in further trials involving antipsychotics in chronic [1460 patients] and first-episode patients [1053 patients]. Across different populations, different trials and different antipsychotics - the best-fitting model suggests that symptom response in schizophrenia is underpinned by a single general effect with secondary and minor lower-order effects on specific symptom domains. This single-factor model explained nearly 80% of the variance, was superior to the assumption of unique efficacy for specific domains; and replicated across antipsychotics and illness stages. Despite theoretical and pharmacological claims the differential efficacy of antipsychotics on the various dimensions of schizophrenia is not supported in the prevailing data. The implication of this finding for the measurement of treatment response and our understanding of the neurobiology of antipsychotic action, for clinical practice and for future drug development are discussed.
Cookson, John; Hodgson, Richard; Wildgust, Hiram J
Hyperprolactinaemia is a common side effect of antipsychotics; markedly raised levels are less common. Higher levels of prolactin result from longer exposure to higher doses, especially with older antipsychotics or with risperidone, sulpiride or amisulpride. Galactorrhoea, gynaecomastia, menstrual abnormalities and sexual dysfunction including hypogonadism and fertility problems are consequences of raised prolactin, and in the longer-term bone demineralisation. Younger patients may be more susceptible to hyperprolactinaemia. Trial reports often fail to state the frequency of raised levels.
Worsham, Elizabeth; Haire-Joshu, Debra; Duncan, Alexis; Schweiger, Julia; Yingling, Michael; Lenze, Eric
Abstract Background: Mentally ill youth are at risk for developing obesity, especially when they require antipsychotic treatment; moreover, they may face unique challenges in adhering to behavioral weight loss interventions. The aims of this project were to characterize the challenges families of youth with psychiatric disorders face when engaging in weight loss treatment and to gather information on attitudes and preferences for weight management interventions in this population. Methods: We devised a telephone survey to evaluate caregiver-perceived barriers/challenges to and preferences for behavioral weight loss treatment in overweight or obese mentally ill youth ages 6–18 treated with an antipsychotic agent in an outpatient setting. Results: A total of 26 parents or primary caregivers completed the survey. The most commonly cited barriers to participation in physical activity (PA) and maintaining a healthy diet were child's dislike of PA and child's preference for energy-dense foods, respectively, which were impacted by psychiatric symptoms. Preferences for weight loss treatment included individualized, prescribed meal plans and shopping lists, and exercise support/demonstration, with a preference for Internet or cell phone applications to help with monitoring food intake and exercise. Conclusions: These results suggest that targets for obesity treatment in this population include individualized, specific support that takes into account the child's motivation, which is effected by psychiatric symptoms. Tools for providing support may include the use of telehealth visits and mobile device applications for self-monitoring. PMID:26788619
Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán
Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin
Dhawan, Nikhil; Steele, Avila B.; Morgan, Robert O.; Snow, A. Lynn; Davila, Jessica A.; Kunik, Mark E.
Objective: The purpose of this study was to determine the prevalence of antipsychotic use among nonaggressive patients with newly diagnosed dementia and to examine indications for antipsychotic use. Method: Patients had to be veterans older than 60 years, newly diagnosed with dementia (ICD-9-CM criteria) from 2001 to 2004 at the Michael A. DeBakey Veterans Affairs Medical Center in Houston, Tex. Patients diagnosed more than 1 year before telephone screening, living in a nursing home or having a caregiver less than 8 hours a week, and/or having aggression, determined by caregiver response on the Ryden Aggression Scale, were excluded. Medical records of eligible participants were then evaluated on the basis of 5 questions: (1) Was the patient taking an antipsychotic? (2) Were neuropsychiatric symptoms documented, with or without antipsychotics? (3) Did the patient have comorbid psychiatric diagnoses? (4) Did the physician attempt to decrease or discontinue the antipsychotic? and (5) Did the physician attempt non-pharmacologic interventions? Results: A total of 173 patients were eligible for medical record evaluation. Of these, 29 (17%) had been prescribed antipsychotics. Depression, nighttime disturbance, and irritability were the most often documented neuropsychiatric symptoms; however, 31% of patients had no documented symptoms. Mood disorder was documented in 36% of patient records; however, 94 patients (54%) had no comorbid psychiatric disorder. Twelve nonpharmacologic interventions were documented for dementia symptoms. Only 2 attempts to discontinue or decrease antipsychotics for the 29 patients using them were documented. Conclusion: A sizable minority of newly diagnosed, nonaggressive dementia patients are taking antipsychotics. Physicians need greater education and awareness of the benefits of nonpharmacologic interventions. PMID:18458729
Apiquian, Rogelio; Fresán, Ana; de la Fuente-Sandoval, Camilo; Ulloa, Rosa-Elena; Nicolini, Humberto
Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs). These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS), risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some Mexican physicians to change
Risser, Amanda; Donovan, Deirdre; Heintzman, John; Page, Tanya
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used, but have risks associated with their use, including significant upper gastrointestinal tract bleeding. Older persons, persons taking anticoagulants, and persons with a history of upper gastrointestinal tract bleeding associated with NSAIDs are at especially high risk. Although aspirin is cardioprotective, other NSAIDs can worsen congestive heart failure, can increase blood pressure, and are related to adverse cardiovascular events, such as myocardial infarction and ischemia. Cyclooxygenase-2 inhibitors have been associated with increased risk of myocardial infarction; however, the only cyclooxygenase-2 inhibitor still available in the United States, celecoxib, seems to be safer in this regard. Hepatic damage from NSAIDs is rare, but these medications should not be used in persons with cirrhotic liver diseases because bleeding problems and renal failure are more likely. Care should be used when prescribing NSAIDs in persons taking anticoagulants and in those with platelet dysfunction, as well as immediately before surgery. Potential central nervous system effects include aseptic meningitis, psychosis, and tinnitus. Asthma may be induced or exacerbated by NSAIDs. Although most NSAIDs are likely safe in pregnancy, they should be avoided in the last six to eight weeks of pregnancy to prevent prolonged gestation from inhibition of prostaglandin synthesis, premature closure of the ductus arteriosus, and maternal and fetal complications from antiplatelet activity. Ibuprofen, indomethacin, and naproxen are safe in breastfeeding women. Care should be taken to prevent accidental NSAID overdose in children by educating parents about correct dosing and storage in childproof containers.
Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314
... studies have compared them to see which ones work better. Our advice: If your depression is not getting better, try other treatments before you try antipsychotics. • Ask your doctor to make sure you do not have other medical and mental health conditions that can cause depression or make it worse— ...
During the last years, a contribution of antipsychotic drugs in the increase of diabetes prevalence in schizophrenic population has been repetitively suggested. The debate focused mainly on the second-generation antipsychotics. The analysis of the scientific literature indicates however that this discussion is not recent and an increase of diabetes prevalence in schizophrenic populations was already described before the introduction of neuroleptics. Then, after the introduction of the first neuroleptics in the 1950s, an increase of diabetes prevalence was reported among treated patients and the same alarms occurred in the 1990s after the introduction of second-generation antipsychotics. These treatments were related to an increase of glucose tolerance impairment, type II diabetes and diabetic acidoketosis. Recent epidemiological studies have confirmed the increase prevalence of diabetes in schizophrenic patients, particularly in schizophrenic patients before any antipsychotic treatment. Among the suggested mechanisms, there are sedentary life (due to hospitalisation and sedative effects of neuroleptics), food imbalance, shared genetic factors for diabetes and schizophrenia. Moreover, the frequency of the metabolic syndrome is increased in schizophrenic populations. This syndrome associates blood glucose increase, lipid metabolism disorders and android obesity. This could explain--via an increase of the cortisol production--the increase of mortality due to cardiovascular diseases observed in schizoprhenic patients. Thus, it seems well established that schizophrenia is associated with an increased risk for diabetes. It is however more difficult to evaluate the role of antipsychotic treatment as a causative factor of diabetes. Indeed, there are many published case reports or diabetes or diabetic acidoketosis after an antipsychotic treatment, but the level of evidence in controlled trials is low. Many studies were performed on large databases, but were retrospective
Sandberg, Larry S
The value of medication for some patients in psychoanalysis serves to highlight the potential challenges of the medical analyst and invites exploration into possible motivations for assuming the prescribing role. Prescribing medication is one way in which the medical analyst integrates the dual identities of physician and analyst while dealing with significant cultural influences and intrapsychic tensions. Technical challenges posed by assuming the prescribing role are explored, as are the potential benefits of split treatment. The educational implications of this argument are discussed in relation to identity formation for candidates who are physicians.
Gupta, Aditi; Dadheech, Gora; Yadav, Dharamveer; Sharma, Praveen; Gautam, Shiv
Schizophrenia is a psychotic disorder with a complex pathophysiology and requires treatment that includes long term administration of antipsychotics that is said to be associated with metabolic syndrome. This study was designed to evaluate the impact of seven different antipsychotics prescribed to schizophrenic patients, on development of metabolic syndrome in the patients. A total of 210 patients with schizophrenia (30 patients in each drug therapy group) were recruited according to ICD-10 criteria and were assigned to receive the drug for 16 weeks. Measurement of anthropometric (body weight, waist circumference, blood pressure) and biochemical parameters (glucose, insulin, HOMA-IR, triglycerides, LDL, HDL) was done and the patients were subjected to ATP-III defined criteria for metabolic syndrome. Patients undergoing treatment with olanzapine were more prone to metabolic syndrome as the drug induces weight gain after 16 weeks of treatment. It also induces dyslipidemia (P < 0.001) and hyperglycemia (P < 0.01). Clozapine was found to be second most potent drug in inducing metabolic syndrome as the weight in clozapine treated patients increased after 16 weeks, along with a significant increase in glycemic (P < 0.001) and lipid parameters (P < 0.01). Aripriazole and amisulphride are comparatively safer drugs as their role in inducing metabolic abnormalities in schizophrenic patients was insignificant, although the impact of long term administration of these drugs needs to be explored. It is clear from the study that antipsychotic treatment induces metabolic syndrome so, it becomes important that the metabolic and cardiovascular risk factors should be surveillance regularly in schizophrenic patients undergoing antipsychotic treatment.
Strejilevich, Sergio A; Palatnik, Ana; Avila, Rubén; Bustin, Julián; Cassone, Julieta; Figueroa, Soledad; Gimenez, Mariana; de Erausquin, Gabriel A
We compared symptom severity and quality of life (QOL) in schizophrenic patients adequately treated with typical antipsychotics (TAP) or clozapine (CZP). Groups did not differ in symptom severity or QOL. Clozapine caused fewer extrapyramidal symptoms. Negative and extrapyramidal symptoms predicted QOL. Similar outcome in both groups suggests a common ceiling to antipsychotic efficacy.
Lake, Johanna K; Denton, Danica; Lunsky, Yona; Shui, Amy M; Veenstra-VanderWeele, Jeremy; Anagnostou, Evdokia
This study aimed to describe rates of antipsychotic medication use and the association between their use and demographics, clinical variables, and the use of behavioral/education services among children with ASD. For children with ASD ages 2-11 (n = 4749) and those 12-17 (n = 401), 5.4 and 17.7% were prescribed at least one atypical antipsychotic medication respectively. In the multivariable model of young children, older age, use of multiple psychotropic medications, prior ASD diagnosis, non-white Hispanic race/ethnicity, and oppositional defiant problems were associated with antipsychotic use. Among older children, only older age was associated with antipsychotic use. In at least one age group, antipsychotic medication use was also related to behaviour, family and occupational therapy, public insurance, site region, externalizing problems, body mass index, and sleep and gastrointestinal problems.
Worley, Julie; Johnson, Mary; Karnik, Niranjan
Doctor shopping is a primary method of prescription medication diversion. After opioids, benzodiazepines and stimulants are the next most common prescription medications used nonmedically. Studies have shown that patients who engage in doctor shopping find it fun, exciting, and easy to do. There is a lack of research on the prescriber's perspective on the phenomenon of doctor shopping. This study investigates the experiences of prescribers in psychiatry with patients who engage in doctor shopping. Fifteen prescribers including psychiatrists and psychiatric nurse practitioners working in outpatient psychiatry were interviewed to elicit detailed information about their experiences with patients who engage in doctor shopping. Themes found throughout the interview were that psychiatric prescribers' experience with patients who engage in doctor shopping includes (a) detecting red flags, (b) negative emotional responding, (c) addressing the patient and the problem, and (d) inconsistently implementing precautions. When red flags were detected when prescribing controlled drugs, prescribers in psychiatry experienced both their own negative emotional responses such as disappointment and resentment as well as the negative emotions of the patients such as anger and other extreme emotional responses. Psychiatric prescribers responded to patient's doctor shopping in a variety of ways such as changing their practice, discharging the patients or taking steps to not accept certain patients identified as being at risk for doctor shopping, as well as by talking to the patient and trying to offer them help. Despite experiencing doctor shopping, the prescribers inconsistently implemented precautionary measures such as checking prescription drug monitoring programs.
Lindh, Jonatan D.
Background: Although therapeutic drug monitoring (TDM) is considered an underused tool in psychiatric care, the prevalence of TDM is largely unknown. The aim of this study was to analyze the prevalence of TDM for antidepressants and antipsychotics during 2006–2013. Methods: The study population consisted of individuals ≥5 years of age residing in Stockholm County. The prevalence of TDM for each study year was calculated with the number of individuals in whom TDM had been performed as nominator (extracted from the TDM database at Karolinska University Laboratory) and the number of treated individuals as denominator (extracted from the Swedish Prescribed Drug Register). All data were obtained at the third and the fifth level of the anatomical therapeutic chemical classification system (pharmacological subgroup and chemical substance, respectively). The prevalence of TDM was compared between substances according to the level of TDM recommendation by guidelines. Results: For antidepressants, the prevalence of TDM decreased from 0.48% (95% confidence interval, 0.45%–0.52%) in 2006 to 0.36% (0.33%–0.39%) in 2013 (among 133,275 and 162,998 treated individuals, respectively). For antipsychotics, the prevalence of TDM increased from 2.3% (2.2%–2.5%) to 4.1% (3.9%–4.3%) (31,463 and 32,534 treated individuals). For both drug groups, TDM was more common in men than in women. The most frequently analyzed drugs were clozapine, perphenazine, zuclopenthixol, nortriptyline, and flupentixol. Although not reaching statistical significance, the TDM prevalence was greater for substances strongly recommended for TDM than for substances with a lower level of recommendation, median (interquartile range): 5.6% (2.8%–22%) versus 1.1% (0.2%–2.2%), P = 0.063. Conclusions: The prevalence of TDM is generally low, more frequent, and increasing for antipsychotics, and more frequent for men and substances where TDM is strongly recommended. PMID:25533882
Donohoe, Dallas R; Weeks, Kathrine; Aamodt, Eric J; Dwyer, Donard S
Antipsychotic drugs are increasingly being prescribed for children and adolescents, and are used in pregnant women without a clear demonstration of safety in these populations. Global effects of these drugs on neurodevelopment (e.g., decreased brain size) have been reported in rats, but detailed knowledge about neuronal effects and mechanisms of action are lacking. Here we report on the evaluation of a comprehensive panel of antipsychotic drugs in a model organism (Caenorhabditis elegans) that is widely used to study neuronal development. Specifically, we examined the effects of the drugs on neuronal migration and axonal outgrowth in mechanosensory neurons visualized with green fluorescent protein expressed from the mec-3 promoter. Clozapine, fluphenazine, and haloperidol produced deficits in the development and migration of ALM neurons and axonal outgrowth in PLM neurons. The defects included failure of neuroblasts to migrate to the proper location, and excessive growth of axons past their normal termination point, together with abnormal morphological features of the processes. Although the antipsychotic drugs are potent antagonists of dopamine and serotonin receptors, the neurodevelopmental deficits were not rescued by co-incubation with serotonin or the dopaminergic agonist, quinpirole. Other antipsychotic drugs, risperidone, aripiprazole, quetiapine, trifluoperazine and olanzapine, also produced modest, but detectable, effects on neuronal development. This is the first report that antipsychotic drugs interfere with neuronal migration and axonal outgrowth in a developing nervous system.
Demland, Jeffery A.; Jing, Yonghua; Kelton, Christina M. L.; Guo, Jeff J.; Li, Hong; Wigle, Patricia R.
Background Postmarketing surveillance that identifies patients at high risk for receiving off-label medications will help ensure that the benefits of such treatment outweigh the risks. Because many off-label uses have little scientific support, tracking the extent to which they occur as well as the particular circumstances under which they occur is important. Objective To describe the drug-use pattern for patients with bipolar disorder, and to identify demographic and clinical factors associated with off-label use of atypical antipsychotics before US Food and Drug Administration approval for this indication. Methods Using the PHARMetrics medical claims database, a total of 105,771 adult patients with a diagnosis of bipolar disorder were evaluated during the 5-year (1998–2002) study period. Study drugs included mood stabilizers, antipsychotics, and antidepressants. Off-label use of an atypical antipsychotic was defined as a patient taking olanzapine before March 2000 (when it received an indication for bipolar disorder) or any other atypical antipsychotic during the entire study period. Logistic regression analysis was used to determine the odds ratio of receiving a drug off-label. Results Utilization of and reimbursement for atypical antipsychotics increased during the 5-year period. Of the 10.5% of patients who took atypical antipsychotics, 7.1% took these drugs off-label. In addition, 11% of patients received lithium, 25% received other anticonvulsants, and 34% received antidepressants. Off-label use of atypical antipsychotics was associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI, 1.44–1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51; 95% CI, 1.38–1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14–1.26), diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16–1.37), cerebral vascular disease (odds ratio = 1.26; 95% CI, 1.10–1.45), and hypertension (odds ratio = 1.12; 95% CI, 1.05–1.20). Over
Thiboutot, Zoé; Perreault, Marc M; Williamson, David R; Rose, Louise; Mehta, Sangeeta; Guenette, Melanie D; Cook, Deborah; Burry, Lisa
Background: Critically ill patients frequently experience delirium, and antipsychotic drugs are often used to manage symptoms. Objectives: To describe the use of antipsychotic drugs and delirium screening tools in mechanically ventilated, critically ill adult patients in Canadian intensive care units (ICUs) and to identify factors associated with the use of antipsychotic drugs. Methods: Pharmacists from 51 Canadian ICUs prospectively collected data on antipsychotic use and delirium screening in all patients for whom invasive mechanical ventilation was initiated during a chosen 2-week period occurring sometime in 2008 or 2009. Results: Data were collected for a total of 712 patients, of whom 115 (16.2%) received at least one dose of an antipsychotic. The antipsychotic prescribed, the total daily dose, and the administration schedule varied across sites. Delirium screening tools, validated for use in mechanically ventilated patients and endorsed by professional society guidelines, were part of routine care in a minority of ICUs (7/51 [13.7%]), and delirium screening was documented for few patients overall (41/712 patients [5.8%]). In a multivariable analysis, administration of antipsychotics was independently associated with longer duration of mechanical ventilation (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.07–1.17), daily interruption of sedation (OR 1.71, 95% CI 1.01–2.90), and use of physical restraints (OR 2.15, 95% CI 1.27–3.65). Conclusion: A minority of mechanically ventilated patients in Canadian ICUs received antipsychotic drugs, and screening for delirium with validated tools was rare. Antipsychotic drug use was independently associated with longer duration of mechanical ventilation, daily interruption of sedation, and use of physical restraints. PMID:27168631
Lesar, Timothy S
CONTEXT Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic evaluations of the characteristics of errors related to medication dosage formulation have been performed. OBJECTIVE To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication dosage forms . DESIGN Evaluation of all detected medication prescribing errors involving or related to medication dosage forms in a 631-bed tertiary care teaching hospital. MAIN OUTCOME MEASURES Type, frequency, and potential for adverse effects of prescribing errors involving or related to medication dosage forms. RESULTS A total of 1,115 clinically significant prescribing errors involving medication dosage forms were detected during the 60-month study period. The annual number of detected errors increased throughout the study period. Detailed analysis of the 402 errors detected during the last 16 months of the study demonstrated the most common errors to be: failure to specify controlled release formulation (total of 280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%) and when prescribing using the generic name (132 cases; 32.8%); and prescribing controlled delivery formulations to be administered per tube (48 cases; 11.9%). The potential for adverse patient outcome was rated as potentially “fatal or severe” in 3 cases (0.7%), and “serious” in 49 cases (12.2%). Errors most commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS Hospitalized patients are at risk for adverse outcomes due to prescribing errors related to inappropriate use of medication dosage forms. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors. PMID:12213138
Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink
Davies, Neil M; Jones, Tim; Kehoe, Patrick G; Martin, Richard M
Introduction Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. Methods and analysis We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. Ethics and dissemination This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate. PMID:27965247
It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…
Tranulis, Constantin; Skalli, Leila; Lalonde, Pierre; Nicole, Luc; Stip, Emmanuel
Combination antipsychotic prescription is an increasingly common practice in clinical psychiatry. This clinical practice is at odds with clinical guidelines promoting antipsychotic monotherapy. Moreover, there has been increased concern over the safety profile of atypical antipsychotics in the last 10-15 years. We reviewed the literature on antipsychotic combinations with a focus on safety and efficacy. Multiple electronic database searches were complemented by relevant bibliography cross-checking and expert discussions. The review showed a literature that is dominated by case reports and uncontrolled studies. Polypharmacy was unequally studied, with some recent combinations (i.e. clozapine and risperidone) being extensively, albeit inconclusively, studied and other more commonly used combinations (first- with second-generation agents) receiving little attention. From an evidence-based perspective, further trials of antipsychotic association of sufficient power to address safety issues are needed before recommending any antipsychotic combination. Particular weaknesses of the present literature are low number of participants, lack of adequate control of confounding variables, short duration of experimental follow-up and inadequate monitoring of potential adverse effects.
McKenna, Kate; Einarson, Adrienne; Levinson, Andrea; Gideon, Koren
Atypical antipsychotics are less likely to cause hyperprolactinemia-related side effects, such as infertility; hence it is predicted that more women taking antipsychotic medications will be able to become pregnant as the use of atypical antipsychotics increases. To compare the use of conventional and atypical antipsychotics, we conducted a retrospective review of the Motherisk Program clinic schedule from 1989 to 2001 comparing the proportion of appointments made for conventional and atypical antipsychotics. In 1989, 2.7% of all appointments were about the use of antipsychotic medication. In 2001, 7.4% of appointments were regarding antipsychotic drug use. This 170% increase was due to an increase in appointments for atypical antipsychotics as the number of appointments for conventional antipsychotics remained relatively constant over the 12-y period. Since the introduction of atypical antipsychotics, more women requiring antipsychotic drug therapy have been planning or becoming pregnant. This increase may have substantial public health implications.
Saar, Eva; Beyer, Jochen; Gerostamoulos, Dimitri; Drummer, Olaf H
The post mortem redistribution of ten commonly prescribed antipsychotic drugs (APs) was investigated. Femoral blood was collected from 273 cases at admission to mortuary (AD) and at post-mortem (PM). The PM samples were collected at various times up to nine days after admission and the sample pairs analysed using LC-MS/MS. The drugs included in this study were 9OH-risperidone (paliperidone), amisulpride, chlorpromazine, clozapine, haloperidol, olanzapine, promethazine, quetiapine, risperidone, and zuclopenthixol. Haloperidol, quetiapine and risperidone showed minimal changes between AD and PM specimens, whereas the majority of drugs showed significant changes between the sample pairs collected at different time points post mortem (p<0.01) in addition to an average concentration change greater than the uncertainty of measurement of the applied method. Average increases in blood concentrations after admission to the mortuary ranged up to 112% (chlorpromazine and olanzapine) but also decreases up to -43% (9OH-risperidone) were seen. There were large standard deviations between sample pairs and substantial day-to-day unpredictable changes that highlight the difficulty in the interpretation of drug concentrations post-mortem. Based on the presented data, we recommend that specimens for toxicological analysis should to be taken as soon as possible after admission of a deceased person to the mortuary in order to minimise the effects of the PM interval on the drug concentration in blood.
Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications
Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A.; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique
Purpose The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. Method A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. Results The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. Conclusions In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system. PMID:27764107
Whale, Richard; Harris, Michael; Kavanagh, Gail; Wickramasinghe, Vijitha; Jones, Christopher I.; Marwaha, Steven; Jethwa, Ketan; Ayadurai, Nirmalan; Thompson, Andrew
Background One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP). Aims To investigate the effectiveness of commonly used antipsychotic medications in FEP. Method A retrospective cohort study of naturalistic treatment of patients (N=460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files. Results Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation. Conclusions Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus. Declaration of interest R.W., A.T. and S.M. have received research grant, speaker honoraria and conference attendance funding from all companies marketing antipsychotics. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27733935
Kennedy, William Klugh; Jann, Michael W; Kutscher, Eric C
Atypical antipsychotics [also known as second-generation antipsychotics (SGAs)] have become a mainstay therapeutic treatment intervention for patients with schizophrenia, bipolar disorders and other psychotic conditions. These agents are commonly used with other medications--most notably, antidepressants and antiepileptic drugs. Drug interactions can take place by various pharmacokinetic, pharmacodynamic and pharmaceutical mechanisms. The pharmacokinetic profile of each SGA, especially with phase I and phase II metabolism, can allow for potentially significant drug interactions. Pharmacodynamic interactions arise when agents have comparable receptor site activity, which can lead to additive or competitive effects without alterations in measured plasma drug concentrations. Additionally, the role of drug transporters in drug interactions continues to evolve and may effect both pharmacokinetic and pharmacodynamic interactions. Pharmaceutical interactions occur when physical incompatibilities take place between agents prior to drug absorption. Approximate therapeutic plasma concentration ranges have been suggested for a number of SGAs. Drug interactions that markedly increase or decrease the concentrations of these agents beyond their ranges can lead to adverse events or diminished clinical efficacy. Most clinically significant drug interactions with SGAs occur via the cytochrome P450 (CYP) system. Many but not all drug interactions with SGAs are identified during drug discovery and pre-clinical development by employing a series of standardized in vitro and in vivo studies with known CYP inducers and inhibitors. Later therapeutic drug monitoring programmes, clinical studies and case reports offer methods to identify additional clinically significant drug interactions. Some commonly co-administered drugs with a significant potential for drug-drug interactions with selected SGAs include some SSRIs. Antiepileptic mood stabilizers such as carbamazepine and valproate, as
Chen, Chien-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin
Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed. PMID:27489377
Sárvári, Anitta K; Veréb, Zoltán; Uray, Iván P; Fésüs, László; Balajthy, Zoltán
Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state.
Goodnick, Paul J; Rodriguez, Lucero; Santana, Orlando
Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis. Since the mid-1970s, the impact of antipsychotics on human prolactin (hPrl) levels has been investigated. Baseline levels of hPrl were found to be similar in healthy controls and patients who were diagnosed as having schizophrenia. Short-term acute studies done after single parenteral or oral doses of phenothiazines found rapid two- to tenfold increases in hPrl. Similar increases were found in longer term studies that reported increases of three times in both men and women after 3 days that doubled again after several weeks of treatment. A study of longer term injectable fluphenazine enanthate found that elevation induced by a single injection lasted up to 28 days. The same results with significant increases have been reported with the butyrophenone, haloperidol. Substantial increases are found after single injections (up to nine times) and after weeks of treatment (up to three times sustained). Thus, early literature believed that there might be an association between these induced changes and response to therapy. However, prolactin is secreted by the anterior pituitary and is under inhibitory control of dopamine released from the tuberoinfundibular neurones. Thus, increases in prolactin are due to antipsychotic impact on tuberoinfundibular tract, one of four dopamine-related tracts. With the application of clozapine and other atypical antipsychotics, it was found that medications can successfully treat psychosis without increasing hPrl. In fact, early single-dose trails found clozapine to reduce hPrl by 16%. Later studies replicated this result and also found that up to 6 weeks of administration led to reductions in hPrl of up to 80%. Risperidone, however, has been found to persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have
Smith, Marie; Dang, Devra; Lee, Jennifer
With the recent Center for Medicare and Medicaid Services and stimulus package incentives for health information technology, many clinicians are expected to adopt or enhance their use of e-prescribing systems. E-prescribing has nearly eradicated medication errors resulting from prescriber handwriting interpretations, yet several other patient-care and workflow benefits still remain a promise. As prescribers select or update their e-prescribing systems (whether stand-alone or integrated with electronic health records), close attention is needed to the e-prescribing application features and level of clinical decision support to avoid clinical blind spots, including incomplete or inaccurate patient medication lists, poor drop-down menu or screen design, and lack of clinically relevant and actionable drug interaction and drug allergy alerts. This article presents three case studies that highlight common e-prescribing problems involving diabetes patients. PMID:20144439
Peuskens, J; Pani, L; Detraux, J; De Hert, M
Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966-December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the
Bordia, Tanuja; McIntosh, J Michael; Quik, Maryka
Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.
Macarthur, Colin; Rockwood, Kenneth
Drug-induced iatrogenic disease is more common among elderly patients than in any other patient population. Factors associated with adverse drug reactions in the elderly include excessive and inappropriate prescribing practices (such as the failure to adjust drug dose to age or complex drug regimens), the aging process itself (altered pharmacokinetics and pharmacodynamics), and concurrent illness. PMID:21229126
Binkowska-Bury, Monika; Więch, Paweł; Bazaliński, Dariusz; Marć, Małgorzata; Bartosiewicz, Anna; Januszewicz, Paweł
Abstract The aim of this study was to identify and examine the differences in opinions held by health care professionals and the general public concerning the right to administer and prescribe medication which has been awarded to nurses and midwives in Poland. The study was conducted from December 1, 2014 to July 1, 2015, in randomly selected primary health care clinics, among 2227 individuals, including 849 subjects representing medical personnel of primary health care and 1378 patients receiving primary care services. The study used 2 versions of a questionnaire. The relationships were examined with χ2 test for independence and Kruskal–Wallis test. Health professionals do not believe the new rights awarded to nurses and midwives will reduce the waiting time for medical consultations (P < 0.001). Nurses’ qualifications for the new tasks were most highly rated by patients, whereas the least favorable opinion was expressed by doctors (P < 0.001). To introduce nurse prescribing it is necessary to develop a suitable strategy enabling implementation of the government's initiative and facilitating the process of taking up the new task by nurses. PMID:27537573
Antipsychotic Drugs for Schizophrenia and Bipolar Disorder: What You Should Know What are antipsychotic drugs? Antipsychotics are prescription drugs used to treat schizophrenia. They can also be used— ...
Harding, Rosie; Peel, Elizabeth
This paper explores the legal position of the off-label prescription of antipsychotic medications to people with dementia who experience behavioural and psychological symptoms of dementia (BPSD). Dementia is a challenging illness, and BPSD can be very difficult for carers to manage, with evidence that this contributes to carer strain and can result in the early institutionalisation of people with dementia. As a result, the prescription of antipsychotic and other neuroleptic medications to treat BPSD has become commonplace, in spite of these drugs being untested and unlicensed for use to treat older people with dementia. In recent years, it has become apparent through clinical trials that antipsychotic drugs increase the risk of cerebrovascular accident (stroke) and death in people with dementia. In addition, these types of medication also have other risk factors for people with dementia, including over-sedation and worsening of cognitive function. Drawing on recent questionnaire (n = 185), focus group (n = 15), and interview (n = 11) data with carers of people with dementia, this paper explores the law relating to off-label prescription, and the applicability of medical negligence law to cases where adverse events follow the use of antipsychotic medication. It is argued that the practice of off-label prescribing requires regulatory intervention in order to protect vulnerable patients.
Kim, Meelee; McDonald, Ann; Kreiner, Peter; Kelleher, Stephen J; Blackman, Michael B; Kaufman, Peter N; Carrow, Grant M
Objective To better understand barriers associated with the adoption and use of electronic prescribing of controlled substances (EPCS), a practice recently established by US Drug Enforcement Administration regulation. Materials and methods Prescribers of controlled substances affiliated with a regional health system were surveyed regarding current electronic prescribing (e-prescribing) activities, current prescribing of controlled substances, and expectations and barriers to the adoption of EPCS. Results 246 prescribers (response rate of 64%) represented a range of medical specialties, with 43.1% of these prescribers current users of e-prescribing for non-controlled substances. Reported issues with controlled substances included errors, pharmacy call-backs, and diversion; most prescribers expected EPCS to address many of these problems, specifically reduce medical errors, improve work flow and efficiency of practice, help identify prescription diversion or misuse, and improve patient treatment management. Prescribers expected, however, that it would be disruptive to practice, and over one-third of respondents reported that carrying a security authentication token at all times would be so burdensome as to discourage adoption. Discussion Although adoption of e-prescribing has been shown to dramatically reduce medication errors, challenges to efficient processes and errors still persist from the perspective of the prescriber, that may interfere with the adoption of EPCS. Most prescribers regarded EPCS security measures as a small or moderate inconvenience (other than carrying a security token), with advantages outweighing the burden. Conclusion Prescribers are optimistic about the potential for EPCS to improve practice, but view certain security measures as a burden and potential barrier. PMID:21946239
Thakkar, Karan B.; Jain, Mangal M.; Billa, Gauri; Joshi, Abhijit; Khobragade, Akash A.
Background: Psychiatric disorders are one of the major causes of morbidity. Development of newer drugs like SSRIs and atypical antipsychotics has altered the treatment paradigms. Various factors like cost of drugs, local paradigms, etc. play a role in the selection of drug therapy and hence, affect the outcome. Keeping this in mind, we conducted a study to delineate the various drugs used in psychiatric disorders, to find discrepancies, if any, between the actual and the ideal prescribing pattern of psychotropic drugs and to conduct a cost analysis. Material and Methods: After our institutional ethics committee approved, a retrospective cross sectional drug utilization study of 600 prescriptions was undertaken. Preparation of the protocol and conduct of the study was as per the WHO – DUS and the STROBE guidelines. Results: Drug use indicators – In 600 prescriptions, 1074 (88.25%) were psychotropic drugs. The utilization from the National and WHO EML was 100% and 90%, respectively. Average number of psychotropic drugs per prescription was 1.79 ± 1.02 (SD). 22.5% of the prescriptions contained psychotropic FDCs. 76.01% of drugs were prescribed by generic name. Percentage of psychotropic drugs prescribed from the hospital drug schedule and psychotropic drugs actually dispensed from the hospital drug store were 73.1% and 62.3%, respectively. Drug utilization pattern in different psychiatric disorders – Most commonly prescribed drugs for schizophrenia, bipolar disorders, depression and anxiety disorders were trifluoperazine + trihexiphenydyl (63.9%), carbamazepine (17.2%), amitriptyline (34.9%), and diazepam (23.8%), respectively. The least commonly prescribed drugs were levosulpiride (1.7%), lithium (1.3%), bupropion (4.7%) and clozapine (1.9%), respectively. The PDD/DDD ratio of three drugs – haloperidol, pimozide and amitriptyline – was equal to one. The cost borne by the hospital was 116, i.e., 65.2% of the total cost. The cost index of clozapine was 11
Johnson, S A; Luu, N T; Herbst, T A; Knapp, R; Lutz, D; Arai, A; Rogers, G A; Lynch, G
Tests were made for interactions between antipsychotic drugs and compounds that enhance synaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors ("ampakines"). Typical and atypical antipsychotic drugs decreased methamphetamine-induced hyperactivity in rats; the effects of near or even subthreshold doses of the antipsychotics were greatly enhanced by the ampakines. Interactions between the ampakine CX516 and low doses of different antipsychotics were generally additive and often synergistic. The ampakine did not exacerbate neuroleptic-induced catalepsy, indicating that the interaction between the different pharmacological classes was selective. These results suggest that positive modulators of cortical glutamatergic systems may be useful adjuncts in treating schizophrenia.
Maayan, Lawrence; Correll, Christoph U.
Despite variations across individuals and agents, antipsychotics are associated with clearly documented weight gain and adverse metabolic effects. Although increased appetite/caloric intake and various receptors, hormones and peptides have been implicated, biological mechanisms contributing to the increase in weight and glucose and lipid abnormalities with antipsychotics are largely unknown. This has hampered the creation of antipsychotics that are free of cardiometabolic effects, even in antipsychotic-naïve/early-phase patients, as well as the development of strategies that can prevent or drastically diminish the adverse cardiometabolic effects. In general, three strategies can reduce the cardiometabolic risk of antipsychotics: 1) switching to a less orexigenenic/metabolically adverse antipsychotic, 2) adjunctive behavioral treatments and 3) adjunctive pharmacologic interventions. However each of these strategies has only been modestly effective. Among different behavioral interventions (N=14, n=746), group and individual treatment, dietary counseling and cognitive-behavioral therapy seem to be similarly effective. Among 15 different pharmacologic strategies (N=35 , n=1,629), only metformin, fenfluramine, sibutramine, topiramate and reboxetine were more effective than placebo, with the most evidence being available for metformin, yet without any head-to-head trials comparing individual pharmacologic interventions. Even in the most successful trials, however, the risk reduction was modest. Weight was not decreased to a pre-treatment level, and despite superiority compared to placebo, weight gain still often occurred, particularly in antipsychotic-naïve patients and when interventions were “preventively” co-initiated with antipsychotics. Future research should focus on combining treatment modalities or agents and on exploring novel mechanism-based interventions. PMID:20586697
Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole and amisulpride, all disrupt active maternal responses (e.g. pup retrieval, pup licking and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at the clinical relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, while 5-HT2A/2C receptors contributing more to atypical drug-induced disruption. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps to understand the extent and mechanisms of impacts of antipsychotic medications on human maternal care, but also is important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects. PMID:26221833
Greene, Jeremy A
Surveillance of physicians' prescribing patterns and the accumulation and sale of these data for pharmaceutical marketing are currently the subjects of legislation in several states and action by state and national medical associations. Contrary to common perception, the growth of the health care information organization industry has not been limited to the past decade but has been building slowly over the past 50 years, beginning in the 1940s when growth in the prescription drug market fueled industry interest in understanding and influencing prescribing patterns. The development of this surveillance system was not simply imposed on the medical profession by the pharmaceutical industry but was developed through the interactions of pharmaceutical salesmen, pharmaceutical marketers, academic researchers, individual physicians, and physician organizations. Examination of the role of physicians and physician organizations in the development of prescriber profiling is directly relevant to the contemporary policy debate surrounding this issue.
Tesfaye, Siranesh; Debencho, Nigussie; Kisi, Teresa; Tareke, Minale
Background. Despite recommendations by guidelines to avoid combinations of antipsychotics unless after multiple trials of antipsychotic monotherapy, it is quite a common practice to use combinations. This practice leads to unnecessary expenses and exposes the patient to severe drug adverse effects. Methods. An institution based cross-sectional study was conducted from April to May 2014. Systematic random sampling technique was used to select 423 study subjects. Logistic regression analysis was conducted to identify associated factors of antipsychotic polypharmacy among schizophrenia outpatients. Result. The overall prevalence of antipsychotic polypharmacy was found to be 28.2%. Extra pyramidal side effects (AOR = 2.80; 95% CI: 1.38, 5.71), repeated psychiatric hospitalization (AOR = 2.83; 95% CI: 1.45, 5.50), history of substance use (AOR = 2.82; 95% CI: 1.36, 5.88), longer duration of treatment (AOR = 2.10; 95% CI: 1.14, 3.87), and drug nonadherence (AOR = 1.84; 95% CI: 1.14, 2.98) were found to be significantly associated with antipsychotic polypharmacy. Conclusion. Prevalence of antipsychotic polypharmacy was found to be high among the current study participants. Individuals who had extra pyramidal side effects, admission, substance use, duration of treatment, and drug nonadherence were associated with antipsychotic polypharmacy. PMID:26904586
Background The aim of the present study was to describe the use of prescribed and non prescribed medicines in a non-institutionalised population older than 15 years of an urban area during the year 2000, in terms of age and gender, social class, employment status and type of Primary Health Care. Methods Cross-sectional study. Information came from the 2000 Barcelona Health Interview Survey. The indicators used were the prevalence of use of prescribed and non-prescribed medicines in the two weeks prior to the interview. Descriptive analyses, bivariate and multivariate logistic regression analyses were carried out. Results More women than men took medicines (75.8% vs. 60% respectively). The prevalence of use of prescribed medicines increased with age while the prevalence of non-prescribed use decreased. These age differences are smaller among those with poor perceived health. In terms of social class, a higher percentage of men with good health in the more advantaged classes took non-prescribed medicines compared with disadvantaged classes (38.7% vs 31.8%). In contrast, among the group with poor health, more people from the more advantaged classes took prescribed medicines, compared with disadvantaged classes (51.4% vs 33.3%). A higher proportion of people who were either retired, unemployed or students, with good health, used prescribed medicines. Conclusion This study shows that beside health needs, there are social determinants affecting medicine consumption in the city of Barcelona. PMID:20441578
Background Information about antibiotic prescribing practice in primary care is not available for Ireland, unlike other European countries. The study aimed to ascertain the types of antibiotics and the corresponding conditions seen in primary care and whether general practitioners (GPs) felt that an antibiotic was necessary at the time of consultation. This information will be vital to inform future initiatives in prudent antibiotic prescribing in primary care. Methods Participating GPs gathered data on all antibiotics prescribed by them in 100 consecutive patients’ consultations as well as data on the conditions being treated and whether they felt the antibiotic was necessary. Results 171 GPs collected data on 16,899 consultations. An antibiotic was prescribed at 20.16% of these consultations. The majority were prescribed for symptoms or diagnoses associated with the respiratory system; the highest rate of prescribing in these consultations were for patients aged 15–64 years (62.23%). There is a high rate of 2nd and 3rd line agents being used for common ailments such as otitis media and tonsillitis. Amoxicillin, which is recommended as 1st line in most common infections, was twice as likely to be prescribed if the prescription was for deferred used or deemed unnecessary by the GP. Conclusion The study demonstrates that potentially inappropriate prescribing is occurring in the adult population and the high rate of broad-spectrum antimicrobial agents is a major concern. This study also indicates that amoxicillin may be being used for its placebo effect rather than specifically for treatment of a definite bacterial infection. PMID:22640399
Onalaja, Oluwademilade A.
Background Antipsychotics can exacerbate motor symptoms in Parkinson's disease psychosis. Aims To systematically review the literature on the efficacy and acceptability of antipsychotics for Parkinson's disease psychosis. Method Randomised controlled trials comparing an antipsychotic with placebo were systematically reviewed. Results The final selection list included nine studies using quetiapine (3), clozapine (2), olanzapine (3) and pimavanserin (1). A narrative synthesis and meta-analyses (where appropriate) were presented for each antipsychotic. Clozapine demonstrated superiority over placebo in reducing psychotic symptoms. Quetiapine and olanzapine did not significantly improve psychotic symptoms. All three antipsychotics may exacerbate motor symptoms. Quetiapine studies were associated with high drop-out rates due to adverse events. Pimavanserin is a novel treatment that warrants further investigation. Conclusions Further research is needed. Clozapine and pimavanserin appear to be a promising treatment for Parkinson's disease psychosis. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703720
Lawford, Bruce R; Barnes, Mark; Connor, Jason P; Heslop, Karen; Nyst, Phillip; Young, Ross McD
Hyperprolactinaemia in antipsychotic treated patients with schizophrenia is a consequence of D2 receptor (DRD2) blockade. Alcohol use disorder is commonly comorbid with schizophrenia and low availability of striatal DRD2 may predispose individuals to alcohol use. In this pilot study we investigated whether hyperprolactinaemia secondary to pharmacological DRD2 blockade was associated with alcohol use disorder in 219 (178 males and 41 females) patients with schizophrenia. Serum prolactin determinations were made in patients diagnosed with schizophrenia and maintained on antipsychotic agents. Clinical assessment included demographics, family history and administration of the AUDIT (Alcohol Use Disorders Identification Test). Higher AUDIT scores were associated with prolactin-raising antipsychotic medication (n=106) compared with prolactin-sparing medication (n=113). Risperidone (n=63) treated patients had higher AUDIT scores and prolactin levels than those on other atypical antipsychotics (n = 113). Across the entire sample, patients with a prolactin greater than 800 mIU/L had higher AUDIT scores and were more likely to exceed the cut-off score for harmful and hazardous alcohol use. These differences were not explained by potential confounds related to clinical features and demographics, comorbidity or medication side-effects. These data suggest that by lowering dosage, or switching to another antipsychotic agent, the risk for alcohol use disorder in those with schizophrenia may be reduced. This hypothesis requires testing using a prospective methodology.
Panariello, Fabio; De Luca, Vincenzo; de Bartolomeis, Andrea
Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1) the role of polymorphisms in several candidate genes, (2) the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3) the state of development of animal models in this matter. We also outline major areas for future research. PMID:22988505
Lin, Yi-Hsiung; Liu, Chia-Yih; Hsiao, Mei-Chun
Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.
Gareri, Pietro; De Fazio, Pasquale; Stilo, Mariagrazia; Ferreri, Guido; De Sarro, Giovambattista
Psychoses are major mental disorders marked by derangement of personality and loss of contact with reality, and are common in the elderly. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients, the most studied of which are the dopaminergic, serotonergic and glutamatergic systems. In particular, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Treatment with antipsychotics is very common in the elderly and often indispensable. However, for successful treatment it is essential to have an adequate multidimensional assessment of the geriatric patient and of his or her polypathology and polypharmacy, together with knowledge of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug interactions.Conventional antipsychotics such as haloperidol, chlorpromazine, promazine, tiapride and zuclopenthixol are D(2)-receptor antagonists and inhibit dopaminergic neurotransmission in a dose-related manner. They decrease the intensity of all psychotic symptoms, although not necessarily to the same extent and with the same time course. Negative symptoms may persist to a much more striking extent than delusions, hallucinations and thought disorders, and there is a dose-related incidence of extrapyramidal side effects (EPS). Newer antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and ziprasidone, have a different receptor-binding profile, interacting with both D and 5-HT receptors; they less frequently cause EPS and are better tolerated in the elderly. Their use is advantageous because they are effective both on positive and negative symptoms of schizophrenia and may also be used in the treatment of behavioural disturbances in elderly and/or demented individuals. The use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine, risperidone, quetiapine
Rothschild, Jeffrey M; Salzberg, Claudia; Keohane, Carol A; Zigmont, Katherine; Devita, Jim; Gandhi, Tejal K; Dalal, Anuj K; Bates, David W; Poon, Eric G
Objective To report the frequency, types, and causes of errors associated with outpatient computer-generated prescriptions, and to develop a framework to classify these errors to determine which strategies have greatest potential for preventing them. Materials and methods This is a retrospective cohort study of 3850 computer-generated prescriptions received by a commercial outpatient pharmacy chain across three states over 4 weeks in 2008. A clinician panel reviewed the prescriptions using a previously described method to identify and classify medication errors. Primary outcomes were the incidence of medication errors; potential adverse drug events, defined as errors with potential for harm; and rate of prescribing errors by error type and by prescribing system. Results Of 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163 (35.0%) were considered potential adverse drug events. Error rates varied by computerized prescribing system, from 5.1% to 37.5%. The most common error was omitted information (60.7% of all errors). Discussion About one in 10 computer-generated prescriptions included at least one error, of which a third had potential for harm. This is consistent with the literature on manual handwritten prescription error rates. The number, type, and severity of errors varied by computerized prescribing system, suggesting that some systems may be better at preventing errors than others. Conclusions Implementing a computerized prescribing system without comprehensive functionality and processes in place to ensure meaningful system use does not decrease medication errors. The authors offer targeted recommendations on improving computerized prescribing systems to prevent errors. PMID:21715428
Dorado, Pedro; Berecz, Roland; Peñas-Lledó, Eva M; Llerena, Adrián
Although the most common, and usually serious, side effects of first-generation (or typical) antipsychotic drugs, such as Parkinsonism, dystonias and tardive dyskinesia, were known from early times, their cardiovascular safety was not properly in the focus of treatment management. The growing evidence of these drug-related cardiac changes and the appearance of potentially fatal dysrhythmias have increased the interest on their safety profile. Thus, the introduction of the new second-generation (atypical) antipsychotic drugs put emphasis on the preregistration evaluation of the potential cardiac side effects and electrocardiogram predictors (QT interval lengthening). In spite of this, these drugs do not appear to be exempt from these potential risks. The present review summarizes up-to-date knowledge about the cardiac safety of antipsychotic drugs, and analyses the role of drug metabolic processes (CYP2D6 genetic polymorphism) in the complex pathophysiology of the phenomenon. In addition, some recommendations are formulated.
Long-acting injectable (depot) antipsychotics are one approach in the management of individuals with schizophrenia. Since the introduction of risperidone long-acting injection in 2003, three additional second-generation antipsychotics have become available in a long-acting injectable formulation: paliperidone, olanzapine and aripiprazole. Although these different depot options can help with adherence and thus encourage better treatment outcomes, they differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of prefilled syringes, storage needs and postinjection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. After a review of the evidence base, guidance is offered on the appropriate selection among the long-acting injectable formulations of both first and second-generation antipsychotics.
Röder, Christian H; Hoogendam, Janna Marie; van der Veen, Frederik M
In the last decade, functional Magnetic Resonance Imaging (FMRI) has been increasingly used to investigate the neurobiology of schizophrenia. This technique relies on changes in the blood-oxygen-level-dependent (BOLD) - signal, which changes in response to neural activity. Many FMRI studies on schizophrenia have examined medicated patients, but little is known about the effects of antipsychotic medication on the BOLD-signal. In this review we investigated to what extent studies in patients with schizophrenia (SC), who were treated with different antipsychotics, could give insight in the effects of antipsychotics on the BOLD-signal. A PubMed search was performed using the search items "schizophrenia", "FMRI", "antipsychotics" and "schizophrenia", "BOLD", "antipsychotics". Only articles in which there were at least two groups of patients with different treatments or in which patients were scanned twice with different treatments were selected. 18 articles, published between 1999 and 2009, fulfilled these criteria. Paradigms and results of these studies were compared regarding differences induced by the administered antipsychotics. This analysis showed no general effect of antipsychotics on the BOLD-signal. However, there is some evidence that the extent of blockade of the dopamine (DA) D(2) receptor does influence the BOLD-signal. Higher affinity to the dopamine D2 receptor, as expressed by a higher/lower inhibition constant (Ki) seems to cause a decrease in BOLD-signal.
Ghodse, Hamid, Ed.; Khan, Inayat, Ed.
This book presents a wide-ranging analysis of what can be done to reduce the misuse of psychoactive drugs without compromising appreciation for their therapeutic value. Emphasis is placed on the need to give physicians guidelines for deciding to whom to prescribe, what to prescribe, how much, and for how long. Chapter 1 provides an introduction…
Belli, Hasan; Ural, Cenk; Akbudak, Mahir
In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.
Habermann, Frank; Fritzsche, Juliane; Fuhlbrück, Frederike; Wacker, Evelin; Allignol, Arthur; Weber-Schoendorfer, Corinna; Meister, Reinhard; Schaefer, Christof
Women of childbearing age are often affected with psychotic disorders, requiring the use of antipsychotic medication during pregnancy. In the present study, we prospectively followed the pregnancies of 561 women exposed to second-generation antipsychotic agents (SGAs; study cohort) and compared these to 284 pregnant women exposed to first-generation antipsychotic agents (FGAs; comparison cohort I) and to 1122 pregnant women using drugs known as not harmful to the unborn (comparison cohort II). Subjects were enrolled through the Institute's consultation service. Major malformation rates of SGA exposed were higher compared to comparison cohort II (adjusted odds ratio, 2.17; 95% confidence interval, 1.20-3.91), possibly reflecting a detection bias concerning atrial and ventricular septal defects. Postnatal disorders occurred significantly more often in infants prenatally exposed to SGAs (15.6%) and FGAs (21.6%) compared to 4.2% of comparison cohort II. Cumulative incidences of elective terminations of pregnancy were significantly higher in both the study cohort (17%) and comparison cohort I (21%) compared to comparison cohort II (3%), whereas the rates of spontaneous abortions did not differ. The numbers of stillbirths and neonatal deaths were within the reference range. Preterm birth and low birth weight were more common in infants exposed to FGAs. To conclude, our findings did not reveal a major teratogenic risk for SGAs, making the better studied drugs of this group a treatment option during pregnancy. Because neonates exposed to SGAs or FGAs in the last gestational week are at higher risk of postnatal disorders, delivery should be planned in clinics with neonatal intensive care units.
Chanen, Andrew M; Thompson, Katherine N
Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322
Mauri, M.C.; Paletta, S.; Maffini, M.; Colasanti, A.; Dragogna, F.; Di Pace, C.; Altamura, A.C.
This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects. PMID:26417330
Cooper, T B
Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage. Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients. Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest.
Anderson, G M; Lexchin, J
Drug therapy is an integral component of modern medical care, and practising physicians are faced with the difficult task of keeping up with rapid changes in pharmacologic treatments. Recent evidence indicates that prescribing practice is often inconsistent with criteria for safety and effectiveness. Surveys indicate that community-based physicians are not satisfied with current sources of information on prescription drugs. The dissemination of printed material alone does not lead to improved prescribing practice, but specific education and feedback strategies can. To improve prescribing practice in Canada we need to systematically evaluate strategies to change prescribing behaviour, to design quality assurance programs based on proven strategies and to develop collaboration and cooperation among providers, manufacturers, governments and the public. PMID:8625021
Linares, Oscar A; Linares, Annemarie L
We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist pre-scribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety. PMID:21657860
Christian, Robert B; Gaynes, Bradley N; Saavedra, Lissette M; Sheitman, Brian; Wines, Roberta; Jonas, Daniel E; Viswanathan, Meera; Ellis, Alan R; Woodell, Carol; Carey, Timothy S
The use of antipsychotics, particularly second generation antipsychotics, among children and adolescents has increased markedly during the past 20 years. Existing evidence gaps make this practice controversial and hinder treatment decision-making. This article describes and prioritizes future research needs regarding antipsychotic treatment in youth, focusing on within-class and between-class drug comparisons with regard to key population subgroups, efficacy and effectiveness outcomes, and adverse event outcomes. Using as a foundation a recent systematic review of antipsychotic treatment among youth, which was completed by a different Evidence-based Practice Center, we worked with a diverse group of 12 stakeholders representing researchers, funders, health care providers, patients, and families to identify and prioritize research needs. From an initial list of 16 evidence gaps, we enumerated 6 high-priority research needs: 1) long-term comparative effectiveness across all psychiatric disorders; 2) comparative long-term risks of adverse outcomes; 3) short-term risks of adverse events; 4) differentials of efficacy, effectiveness, and safety for population subgroups; 5) comparative effectiveness among those with attention-deficit/hyperactivity disorder and disruptive behavior disorders and common comorbidities; 6) comparative effectiveness among those with bipolar disorder and common comorbidities. In this article, we describe these future research needs in detail and discuss study designs that could be used to address them.
Chowdhry, Unnum; Jacques, Amanda; Karovitch, Alan; Giguère, Pierre; Nguyen, My-Linh
Background: Recent approval of the new oral anticoagulants dabigatran and rivaroxaban has led to rapid changes in anticoagulant prescribing practices. Postmarketing reports have highlighted safety concerns with these agents, and their use outside of evidence-based recommendations was noted at the authors’ centre. Objectives: To determine the incidence of and risk factors associated with inappropriate prescribing of dabigatran and rivaroxaban. Methods: This retrospective cohort study investigated randomly selected dabigatran or rivaroxaban prescriptions for patients admitted to a tertiary teaching hospital between January 2010 and December 2012. Appropriateness of prescribing was determined from the documented indication, drug dosage, patient’s renal function, and presence of drug interactions, if applicable. Results: Among a total of 321 medication orders reviewed, the incidence of inappropriate use was 31.2% (34/109) for dabigatran and 26.9% (57/212) for rivaroxaban. Of the 97 reasons for inappropriate use that were identified, the most common were prescribing for an unapproved indication (49/97 [50.5%]), concomitant prescribing of another anticoagulant (22/97 [22.7%]), and high prescribed dose (9/97 [9.3%]). The prescribing service was found to be an independent risk factor for inappropriate prescribing (p = 0.041). Corrections were made to 23.1% (21/91) of the incorrect regimens before hospital discharge. In a sensitivity analysis using calculated ideal body weight to estimate renal function, the overall incidence of inappropriate prescribing increased to 31.5% (101/321). Conclusions: The proportion of patients with inappropriate prescribing of dabigatran or rivaroxaban in clinical practice was higher than expected. Educational interventions and pharmacy-led initiatives with a focus on appropriate indications, concomitant anticoagulant prescribing, and review of dosage regimens are recommended to improve patient safety. PMID:27402998
Aston, Lydia; Hilton, Andrea; Iqbal, Naveed; Child, Anne; Shaw, Rachel
Objective This study aimed to use qualitative methodology to understand the current role of community pharmacists in limiting the use of antipsychotics prescribed inappropriately for behavioural and psychological symptoms of dementia. Design A qualitative study employing focus groups was conducted. Data were analysed using thematic analysis. Setting 3 different geographical locations in the England. Participants Community pharmacists (n=22). Results The focus groups identified an array of factors and constraints, which affect the ability of community pharmacists to contribute to initiatives to limit the use of antipsychotics. 3 key themes were revealed: (1) politics and the medical hierarchy, which created communication barriers; (2) how resources and remit impact the effectiveness of community pharmacy; and (3) understanding the nature of the treatment of dementia. Conclusions Our findings suggest that an improvement in communication between community pharmacists and healthcare professionals, especially general practitioners (GPs) must occur in order for community pharmacists to assist in limiting the use of antipsychotics in people with dementia. Additionally, extra training in working with people with dementia is required. Thus, an intervention which involves appropriately trained pharmacists working in collaboration with GPs and other caregivers is required. Overall, within the current environment, community pharmacists question the extent to which they can contribute in helping to reduce the prescription of antipsychotics. PMID:26983947
García, Saínza; Martínez-Cengotitabengoa, Mónica; López-Zurbano, Saioa; Zorrilla, Iñaki; López, Purificación; Vieta, Eduard; González-Pinto, Ana
Abstract Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients. PMID:27307187
Lee, Lik Hang N; Choi, Charles; Collier, Abby C; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M
Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.
Background Little is known about the factors influencing treatment choice in psychosis, the majority of this work being conducted with specialists (consultant) in psychiatry. We sought to examine trainees' choices of treatment for psychosis if they had to prescribe it for themselves, their patients, and factors influencing decision-making. Methods Cross-sectional, semi-structured questionnaire-based study. Results Of the 726 respondents (response rate = 66%), the majority chose second-generation antipsychotics (SGAs) if they had to prescribe it for themselves (n = 530, 93%) or for their patients (n = 546, 94%). The main factor influencing choice was perceived efficacy, 84.8% (n = 475) of trainees stating this was the most important factor for the patient, and 77.8% (n = 404) stating this was the most important factor for their own treatment. Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS) were more likely to choose second-generation antipsychotics than those without knowledge of these trials (χ2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0-4.48). Regarding psychotherapy, cognitive behavioural therapy (CBT) was the most popular choice for self (33.1%; n = 240) and patient (30.9%; n = 224). Trainees were significantly more likely to prefer some form of psychotherapy for themselves rather than patients (χ2 = 9.98; p < 0,002; O.R. = 1.54; 95% CIs = 1.18-2.0). Conclusions Trainees are more likely to choose second-generation antipsychotic medication for patients and themselves. Despite being aware of evidence that suggests otherwise, they predominantly base these choices on perceived efficacy. PMID:22463055
Pilkinton, Patricia D; Pilkinton, James C
Correctional facilities are a major provider of mental health care throughout the United States. In spite of the numerous benefits of providing care in this setting, clinicians are sometimes concerned about entering into correctional care because of uncertainty in prescribing practices. This article provides an introduction to prescription drug use, abuse, and diversion in the correctional setting, including systems issues in prescribing, commonly abused prescription medications, motivation for and detection of prescription drug abuse, and the use of laboratory monitoring. By understanding the personal and systemic factors that affect prescribing habits, the clinician can develop a more rewarding correctional practice and improve care for inmates with mental illness.
Sinha, Preeti; Gupta, Anupam; Reddi, V. Senthil Kumar; Andrade, Chittaranjan
Introduction: This is an exploratory study, which aimed to analyze urodynamic findings in patients who are on atypical antipsychotics and present with urinary incontinence (UI) in order to understand the mechanisms of antipsychotic-emergent UI. Patients and Methods: Eight patients (34 ± 7.6 years; five males and three females) diagnosed with schizophrenia or other psychotic disorders, who were on risperidone, olanzapine, or clozapine monotherapy and having UI were recruited. Urodynamic study was performed in all patients. Results: Six out of eight (75%) patients had abnormal urodynamic findings. Three of them had detrusor overactivity (DO) without detrusor-sphincter dyssynergia (DSD); two had DO with DSD; and one had hypoactive detrusor with nonrelaxing sphincter during void phase. The common urinary symptoms were urgency, enuresis, and straining to void urine. Significant postvoid residual urine was found in two patients. Conclusion: The evidence of bladder dysfunction in atypical antipsychotic-emergent UI is similar to that present in patients with neurological disorders. Urinary complaints in patients on antipsychotics thus need to be evaluated and managed systematically using the protocol followed for neurological conditions. PMID:28197002
Grasslands of the central Great Plains developed with periodic fire. Prescribed burning is an important tool for managing grasslands to maintain desirable species composition, increase grazing livestock performance, maintain productivity, and control invasive weeds. The safe and effective use of pre...
Lack of Effect of Stimulant Combination with Second-Generation Antipsychotics on Weight Gain, Metabolic Changes, Prolactin Levels, and Sedation in Youth with Clinically Relevant Aggression or Oppositionality
Penzner, Julie B.; Dudas, Melissa; Saito, Ema; Olshanskiy, Vladimir; Parikh, Umesh H.; Kapoor, Sandeep; Chekuri, Raja; Gadaleta, Dominick; Avedon, Jennifer; Sheridan, Eva M.; Randell, Jane; Malhotra, Anil K.; Kane, John M.
Abstract Background Second-generation antipsychotics (SGAs) are associated with weight gain, metabolic abnormalities, sedation/sleep disturbance, and prolactin abnormalities, especially in youths. Although stimulants have opposing dopamine receptor and adverse effects, it is unclear whether stimulant co-treatment counteracts the therapeutic or side effects of antipsychotics. Methods This was a naturalistic cohort study including 153 antipsychotic trials in youths aged 4–19 (mean, 11.3 ± 3.0) years, started on an SGA for clinically significant aggression or oppositionality associated with oppositional defiant disorder, conduct disorder, disruptive behavior disorder not otherwise specified (NOS), impulse control disorder NOS, intermittent explosive disorder, Tourette's disorder, autistic disorder, and pervasive developmental disorder NOS. Patients underwent fasting assessments of body composition, lipids, glucose, insulin, prolactin, sedation, and general efficacy at baseline, weeks 4, 8, and 12, comparing patients co-prescribed stimulants (n = 71) with those not co-prescribed stimulants (n = 82). Results Patients received risperidone (33.3%), aripiprazole (29.4%), quetiapine (18.4%), olanzapine (11.8%), ziprasidone (5.9%), or clozapine (0.7%). With and without adjustment for differences in baseline variables (sex, prior stimulant use, primary Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] disorders, co-morbid attention-deficit/hyperactivity disorder [ADHD], present in 46.3% of youths not receiving stimulants, and some body composition parameters), patients on versus off stimulants did not differ on any of the assessed outcomes (all p values ≥ 0.1). Conclusions In contrast to guidelines, stimulant use did not precede or accompany antipsychotic use during the current episode of aggression/oppositionality in almost half of those youths who had aggressive/oppositional behavior and a DSM-IV diagnosis of ADHD. At the
Gaetani, L; Yeo, W W
The large number of medications available has complicated the learning of drug therapy for medical students at a time when pharmacology training has been substantially reduced. Attempts to remedy this include: improving the pharmaco-therapeutics curriculum; interactive web-based learning and students developing a personal formulary. The approach adopted by the University of Wollongong Medical School is to integrate clinical pharmacology throughout the course, with the Student Preferred-drugs Formulary linking pharmacology and common diseases. Evidence from other countries suggests this should enhance prescribing by medical graduates.
Bridges, Thomas M.; LeBois, Evan P.; Hopkins, Corey R.; Wood, Michael R.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.
SUMMARY The cholinergic hypothesis of schizophrenia emerged over 50 years ago based on clinical observations with both anticholinergics and pan-muscarinic agonists. Not until the 1990s did the cholinergic hypothesis of schizophrenia receive renewed enthusiasm based on clinical data with xanomeline, a muscarinic acetylcholine receptor M1/M4-preferring orthosteric agonist. In a clinical trial with Alzheimer’s patients, xanomeline not only improved cognitive performance, but also reduced psychotic behaviors. This encouraging data spurred a second clinical trial in schizophrenic patients, wherein xanomeline significantly improved the positive, negative and cognitive symptom clusters. However, the question remained: Was the antipsychotic efficacy due to activation of M1, M4 or both M1/M4? Classical orthosteric ligands lacked the muscarinic receptor subtype selectivity required to address this key question. More recently, functional assays have allowed for the discovery of ligands that bind at allosteric sites, binding sites distinct from the orthosteric (acetylcholine) site, which are structurally less conserved and thereby afford high levels of receptor subtype selectivity. Recently, allosteric ligands, with unprecedented selectivity for either M1 or M4, have been discovered and have demonstrated comparable efficacy to xanomeline in preclinical antipsychotic and cognition models. These data suggest that selective allosteric activation of either M1 or M4 has antipsychotic potential through distinct, yet complimentary mechanisms. PMID:20520852
Rasimas, J.J.; Liebelt, Erica L.
Medications are being used with greater frequency to address pediatric mental health problems, and in recent years atypical antipsychotic (AAP) prescriptions have increased more than any other class. Acute care practitioners must be aware of the pharmacology of AAPs and the conditions, on- and off-label, for which they are prescribed. This involves identifying and managing side effects that manifest both mentally and physically. Although “atypicality” confers a lower risk of movement side effects compared to conventional agents, children are more sensitive than adults to extrapyramidal reactions. Like adults, they also may present with toxic sedation, confusion, cardiovascular dysfunction, and metabolic derangements. Evaluation and management of these toxicities requires an index of suspicion, a careful symptom and medication history, physical examination, and targeted interventions. This review is designed to orient the emergency practitioner to the challenging task of recognizing and treating adverse effects related to acute and chronic atypical antipsychotic exposure in children. PMID:23471213
Parrinello, Michael C
Patients who are taking atypical antipsychotic medications have a high incidence of metabolic complications, including increased weight, waist circumference, blood sugar, lipid levels, and blood pressure. In 2004, the American Diabetic Association and three other associations, including the American Psychiatric Association, developed guidelines to screen for metabolic syndrome, but in practice, adherence to the guidelines varies. This article describes a process to implement the guidelines in a suburban psychiatric day treatment hospital using Rogers' Diffusion of Innovations model. Measurement of waist circumference was identified as an opportunity to improve the current metabolic screening protocol. Post-intervention evaluation revealed increased adherence to the guidelines (0% pre versus 95% post). Adherence to the guidelines demonstrates the effect of the systematic application of Rogers' model on acceptance of practice change. Fully implementing the guidelines meets recommendations for the standard of practice and can improve the health and quality of life of patients prescribed atypical antipsychotic medications.
Wysowski, D K; Baum, C
Data from the National Prescription Audit and the National Disease and Therapeutic Index were used to assess trends in outpatient prescriptions for antipsychotic drugs in the United States from 1976 to 1985. Retail pharmacies dispensed 21 million prescriptions for antipsychotic drugs in 1976 and 19 million in 1985. The three leading antipsychotic drugs-thioridazine, haloperidol, and chlorpromazine-constituted 66% to 69% of antipsychotic prescriptions and, along with trifluoperazine, thiothixene, and fluphenazine, accounted for 90% to 91% of all antipsychotic prescriptions throughout the period studied. Thioridazine was the leading medication, with a consistent third of the market share, while the market share for chlorpromazine decreased from 1976 to 1985 and that for haloperidol increased for the same years. Data also indicate that haloperidol is the antipsychotic drug used most frequently in office-based, private medical practice for patients 60 years of age and older, a declining proportion of women are treated with antipsychotic medications, and use of antipsychotic drugs as monotherapy for the primary diagnosis is increasing. We also obtained data on diagnoses associated with antipsychotic drug use.
Hershenberg, Rachel; Gros, Daniel F; Brawman-Mintzer, Olga
Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60-70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed.
Langebrake, Claudia; Melzer, Simone; Baehr, Michael
The provision of drugs to hospitalised patients is a complex process with the involvement of different healthcare professionals. As pharmacotherapy is (1) one of the most common medical interventions, (2) a high-risk procedure, and (3) affects the majority of hospitalised patients, medication errors have sustainable impact on patient safety. Although medication errors can occur at different stages of drug use (prescribing, dispensing, administration), they are most likely within the prescribing process. According to the Reason's model of accident causation, these errors can be divided into active failures, error-provoking conditions, and latent conditions. Commonly, the complex interaction between lacking knowledge and/or experience, rule-based mistakes, skill-based slips and memory lapses, inadequate working environment (exessive work load, fatigue) as well as poor communication and safety culture is causative for prescribing errors. Therefore, good prescribing should include the following items: Adherence to formal criteria (e. g. avoidance of abbreviations), performance of medication reconciliation, implementation of an electronic prescribing system (computerised physician order entry, CPOE) - preferably combined with a clinical decision support system (CDSS), education and training as well as the establishment of a positive error management culture. The implementation of recommendations to reduce prescribing errors is described on the basis of established processes in hospitals.
Khidir, Hazar; Weiner, Scott G.
Pain is the most common complaint in the emergency department (ED), and emergency physicians face unique challenges in making opioid-related treatment decisions. Medical students and residents experience significant variation in the quality of education they receive both about opioid prescribing as well as substance-use detection and intervention in the ED. To achieve a better standard of education, clinical educators will need to (a) develop a clearer understanding of the risk for aberrant opioid prescribing in the ED, (b) recognize prescribing bias and promote uptake of evidence-based opioid prescribing guidelines in their EDs, and (c) advocate for integrated opioid management and addiction medicine training formally into medical school curricula. PMID:27833673
Trollor, Julian N; Salomon, Carmela; Franklin, Catherine
SUMMARY Mental illness is common in people with intellectual disability. They may also have physical health problems which can affect their mental state. Difficulties in communication can contribute to mental health problems being overlooked. These may present with changes in behaviour. Psychological management is usually preferable to prescribing psychotropic drugs. Behavioural approaches are the most appropriate way to manage challenging behaviour. If a drug is considered, prescribers should complete a thorough diagnostic assessment, exclude physical and environmental contributions to symptoms, and consider medical comorbidities before prescribing. Where possible avoid psychotropics with the highest cardiometabolic burden. Prescribe the minimum effective dose and treatment length, and regularly monitor drug efficacy and adverse effects. There is insufficient evidence to support the use of psychotropics for challenging behaviour. They should be avoided unless the behaviour is severe and non-responsive to other treatments. PMID:27756975
Fodstad, Jill C.; Bamburg, Jay W.; Matson, Johnny L.; Mahan, Sara; Hess, Julie A.; Neal, Daniene; Holloway, Jodie
Atypical antipsychotic medications are commonly used in large-scale residential care facilities for adults with developmental disabilities. While the benefits of this class of psychotropics are noted, debate exists whether the side effect profile of these medications outweigh their therapeutic benefit, especially in those who use them long-term.…
Pasha, Nida; Saeed, Shoaib; Drewek, Katherine
Physical health monitoring of patients receiving antipsychotics is vital. Overall it is estimated that individuals suffering with conditions like schizophrenia have a 20% shorter life expectancy than the average population, moreover antipsychotic use has been linked to a number of conditions including diabetes, obesity, and cardiovascular disease.[1-4] The severity of possible adverse effects to antipsychotics in adults has raised awareness of the importance of monitoring physical health in this population. However, there is little literature available as to the adverse effects of these medications in the child and adolescent community, which make physical health monitoring in this predominantly antipsychotic naïve population even more important. An expert group meeting in the UK has laid down recommendations in regards to screening and management of adult patients receiving antipsychotics, however no specific guidelines have been put in place for the child and adolescent age group. The aim of this audit was to establish whether in-patients receiving antipsychotics had the following investigations pre-treatment and 12 weeks after treatment initiation: body mass index, hip-waist circumference, blood pressure, ECG, urea and electrolytes, full blood count, lipid profile, random glucose level, liver function test, and prolactin. This is in addition to a pre-treatment VTE risk assessment. These standards were derived from local trust guidelines, NICE guidelines on schizophrenia  and The Maudsley Prescribing Guidelines. We retrospectively reviewed 39 electronic case notes in total, of which 24 cases were post intervention. Intervention included the use of a prompting tool. This tool was filed in the physical health files of all patients receiving antipsychotics which was intended as a reminder to doctors regarding their patient's need for physical health monitoring. Professionals involved in the monitoring of such parameters were educated in the importance and
Hassan, Lamiece; Senior, Jane; Frisher, Martin; Edge, Dawn; Shaw, Jenny
While the prevalence of mental illness is higher in prisons than in the community, less is known about comparative rates of psychotropic medicine prescribing. This is the first study in a decade to determine the prevalence and patterns of psychotropic medication prescribing in prisons. It is also the first study to comprehensively adjust for age when making comparisons with the general population. Four East of England prisons, housing a total of 2222 men and 341 women were recruited to the study. On census days, clinical records were used to identify and collect data on all prisoners with current, valid prescriptions for hypnotic, anxiolytic, antipsychotic, antimanic, antidepressant and/or stimulant medication, as listed in chapters 4.1 to 4.4 of the British National Formulary. Data on 280,168 patients were obtained for comparison purposes from the Clinical Practice Research Datalink. After adjusting for age, rates of psychotropic prescribing in prison were 5.5 and 5.9 times higher than in community-based men and women, respectively. We also found marked differences in the individual psychotropic drugs prescribed in prison and community settings. Further work is necessary to determine whether psychotropic prescribing patterns in prison reflect an appropriate balance between managing mental illness, physical health risks and medication misuse.
Smyth, Brendan; Jones, Ceridwen; Saunders, John
SUMMARY The pharmacokinetics of a drug may be altered in patients with renal impairment who require dialysis. Some drugs are contraindicated. The drug’s clearance and therapeutic index determine if a dose adjustment is needed. A lower dose or less frequent dosing may be required. Consult a reference source or the patient’s nephrologist before prescribing. Start at a low dose and increase gradually. If possible give once-daily drugs after dialysis. PMID:27041803
Bond, Christine; Blenkinsopp, Alison; Raynor, David K
There have been widespread changes in society and the roles of professionals. This change is also reflected in health care, where there is now acceptance of the need to involve patients in decision making. In prescribing specifically, the concordance agenda was developed alongside these initiatives to encourage improved medication taking and reduce wastage. However the extent to which these partnerships are delivered in practice remains unclear. This paper explores some of the issues to be considered when preparing patients and professionals for partnership and summarizes the limited evidence of barriers to, and benefits of, this approach. Firstly patients must be given the confidence, skills and knowledge to be partners. They need information about medicines, provided in ways known to be acceptable to them. Likewise professionals may need new skills to be partners. They need to understand the patient agenda and may need training and support to change the ways in which they consult with patients. There are also practical issues such as the perceived increase in time taken when consulting in partnership mode, room layout, computer interfaces and record keeping. Health care professionals other than doctors are also expected to behave in partnership mode, whether this is as prescribers in their own right or in supporting the prescribing of others. Whilst much has been claimed for the benefit of partnership approaches, hard evidence is limited. However whilst there is still much more to understand there will be no going back to the paternalistic model of the mid 20th century. PMID:22621201
Willett, Gilbert M.; Hyde, Jennifer E.; Uhrlaub, Michael B.; Wendel, Cara L.; Karst, Gregory M.
Examined the relative electromyographic (EMG) activity of upper and lower rectus abdominis (LRA) and external oblique (EOA) muscles during five abdominal strengthening exercises. Isometric and dynamic EMG data indicated that abdominal strengthening exercises activated various abdominal muscle groups. For the LRA and EOA muscle groups, there were…
Cerovecki, Anja; Musil, Richard; Klimke, Ansgar; Seemüller, Florian; Haen, Ekkehard; Schennach, Rebecca; Kühn, Kai-Uwe; Volz, Hans-Peter; Riedel, Michael
With the widespread use of atypical or second-generation antipsychotics, switching treatment has become current practice and more complicated, as the pharmacological profiles of these agents differ substantially despite their similarity in being 'atypical'. All share the ability to block dopamine D₂ receptors, and most of them also block serotonin 5-HT2A receptors. Apart from these common features, some atypical antipsychotics are also able to block or stimulate other dopamine or serotonin receptors, as well as histaminergic, muscarinergic or adrenergic receptors. As a result of the varying receptor affinities, in switching or discontinuing compounds several possible pitfalls have to be considered, including the occurrence of withdrawal and rebound syndromes. This article reviews the pharmacological background of functional blockade or stimulation of receptors of interest in regard to atypical antipsychotics and the implicated potential withdrawal and rebound phenomena. A MEDLINE search was carried out to identify information on withdrawal or rebound syndromes occurring after discontinuation of atypical antipsychotics. Using the resulting literature, we first discuss the theoretical background to the functional consequences of atypical antipsychotic-induced blockade or stimulation of neurotransmitter receptors and, secondly, we highlight the clinical consequences of this. We then review the available clinical literature on switching between atypical antipsychotics, with respect to the occurrence of withdrawal or rebound symptoms. Finally, we offer practical recommendations based on the reviewed findings. The systematic evaluation of withdrawal or rebound phenomena using randomized controlled trials is still understudied. Knowledge of pharmacological receptor-binding profiles may help clinicians in choosing adequate switching or discontinuation strategies for each agent. Results from large switching trials indicate that switching atypical antipsychotics can be
The behavior disorders of 54 Japanese individuals with mental retardation receiving antipsychotic medication were compared to 52 subjects receiving anticonvulsants and 202 subjects without medication. Results found the problem behaviors of subjects receiving antipsychotic drugs were more severe and severity of disability was associated with higher…
Yeeles, Ksenija; Bremner, Stephen; Lauber, Christoph; Eldridge, Sandra; Ashby, Deborah; David, Anthony S; O’Connell, Nicola; Forrest, Alexandra; Burns, Tom
Objective To test whether offering financial incentives to patients with psychotic disorders is effective in improving adherence to maintenance treatment with antipsychotics. Design Cluster randomised controlled trial. Setting Community mental health teams in secondary psychiatric care in the United Kingdom. Participants Patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder, who were prescribed long acting antipsychotic (depot) injections but had received 75% or less of the prescribed injections. We randomly allocated 73 teams with a total of 141 patients. Primary outcome data were available for 35 intervention teams with 75 patients (96% of randomised) and for 31 control teams with 56 patients (89% of randomised). Interventions Participants in the intervention group were offered £15 (€17; $22) for each depot injection over a 12 month period. Participants in the control condition received treatment as usual. Main outcome measure The primary outcome was the percentage of prescribed depot injections given during the 12 month intervention period. Results 73 teams with 141 consenting patients were randomised, and outcomes were assessed for 131 patients (93%). Average baseline adherence was 69% in the intervention group and 67% in the control group. During the 12 month trial period adherence was 85% in the intervention group and 71% in the control group. The adjusted effect estimate was 11.5% (95% confidence interval 3.9% to 19.0%, P=0.003). A secondary outcome was an adherence of ≥95%, which was achieved in 28% of the intervention group and 5% of the control group (adjusted odds ratio 8.21, 95% confidence interval 2.00 to 33.67, P=0.003). Although differences in clinician rated clinical improvement between the groups failed to reach statistical significance, patients in the intervention group had more favourable subjective quality of life ratings (β=0.71, 95% confidence interval 0.26 to 1.15, P=0.002). The number of admissions
Galling, Britta; Roldán, Alexandra; Hagi, Katsuhiko; Rietschel, Liz; Walyzada, Frozan; Zheng, Wei; Cao, Xiao‐Lan; Xiang, Yu‐Tao; Zink, Mathias; Kane, John M.; Nielsen, Jimmi; Leucht, Stefan; Correll, Christoph U.
Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta‐analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co‐primary outcomes were total symptom reduction and study‐defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=–0.53, 95% CI: −0.87 to −0.19, p=0.002). However, superiority was only apparent in open‐label and low‐quality trials (both p<0.001), but not in double‐blind and high‐quality ones (p=0.120 and 0.226, respectively). Study‐defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non‐significant in double‐blind and high‐quality studies (both p=0.990). Findings were replicated in clozapine and non‐clozapine augmentation studies. No differences emerged regarding all‐cause/specific‐cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=–0.38, 95% CI: −0.63 to −0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=–0.41, 95% CI: −0.79 to −0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double‐blind/high‐quality evidence for efficacy, except for negative symptom
Calbo, Esther; Alvarez-Rocha, Luis; Gudiol, Francisco; Pasquau, Juan
There are multiple benefits of appropriate antimicrobial prescribing: it has a direct impact on clinical outcomes, avoids adverse effects, is cost effective and, perhaps most importantly, it helps to prevent the emergence of resistance. However, any physician can prescribe antibiotics, which is not the case with other clinically relevant drugs. There is great variability in the prescribing physician's (PP) training, motivation, workload and setting, including accessibility to infectious diseases consultants and/or diagnostic techniques, and therefore there is a high risk of inappropriate prescription. Many antibiotic prescribing errors occur around the selection and duration of treatment. This includes a low threshold for the indication of antibiotics, delayed initiation of treatment when indicated, limited knowledge of local antimicrobial resistance patterns by the PPs, errors in the final choice of dose, route or drug and a lack of de-escalation. Similarly, the prescription of prophylactic antibiotics to prevent surgical site infections, despite being commonly accepted, is suboptimal. Factors that may explain suboptimal use are related to the absence of well-defined protocols, poor knowledge of prophylactic protocols, miscommunication or disagreement between physicians, logistical problems, and a lack of audits. A proper understanding of the prescribing process can guide interventions to improve the PP's practices. Some of the potential interventions included in a stewardship program are education in antimicrobial prescribing, information on the local resistance patterns and accessibility to a qualified infectious diseases consultant.
Joyce, Geoffrey F.; Carrera, Mariana; Goldman, Dana P.; Sood, Neeraj
OBJECTIVE Concerns over rising drug costs, pharmaceutical advertising and potential conflicts of interest have focused attention on physician prescribing behavior. We examine how broadly physicians prescribe within the ten most prevalent therapeutic classes, the factors affecting their choices, and its impact on patient-level outcomes. STUDY DESIGN Retrospective study from 2005 to 2007 examining prescribers with at least five initial prescriptions within a class from 2005–2007. Medical and pharmacy claims are linked to prescriber information from 146 different health plans, reflecting 1,975 to 8,923 unique providers per drug class. METHODS Primary outcomes are the number of distinct drugs in a class initially prescribed by a physician over 1- and 3-year periods, medication possession ratio, and out of pocket costs. RESULTS In 8 of 10 therapeutic classes, the median physician prescribes at least 3 different drugs and less than one in six physicians prescribes only brand drugs. Physicians prescribing only one or two drugs in a class are more likely to prescribe the most advertised drug. Physicians who prescribe fewer drugs are less likely to see patients with other comorbid conditions and varied formulary designs. Prescribing fewer drugs is associated with lower rates of medication adherence and higher out-of-pocket costs for drugs, but the effects are small and inconsistent across classes. CONCLUSIONS Physicians prescribe more broadly than commonly perceived. Though narrow prescribers are more likely to prescribe highly advertised drugs, few physicians prescribe these drugs exclusively. Narrow prescribing has modest effects on medication adherence and out of pocket costs in some classes. PMID:22216870
Gao, Keming; Sheehan, David V; Calabrese, Joseph R
Generalized anxiety disorder (GAD) is a chronic, highly prevalent and debilitating disorder that commonly co-occurrs with mood disorders. Current available agents for GAD are limited either by their slow onsets of actions, unsatisfactory anxiolytic effects or potential for abuse/dependence. Atypical antipsychotics have been studied as alternatives. Olanzapine, risperidone and quetiapine immediate release have been explored in the treatment of refractory GAD and risperidone in bipolar anxiety with randomized, double-blind, placebo-controlled trials, but the results were not consistent. By contrast, quetiapine extended release (quetiapine-XR) 150 mg/day monotherapy yielded consistent anxiolytic effects across three studies that were superior to placebo and as effective as paroxetine 20 mg/day and escitalopram 10 mg/day but with an earlier onset of action. In a 52-week treatment of GAD, quetiapine-XR was superior to placebo in the prevention of anxiety relapses. Overall, atypical antipsychotics were relatively well tolerated, with common side effects of somnolence and sedation. However, in contrast to antidepressants and benzodiazepines, the long-term risk and benefit of atypical antipsychotics in the treatment of GAD is yet to be determined.
Nash, Abigail I
In the setting of rising rates of obesity and metabolic syndrome, characterized in part by hyperinsulinemia, it is increasingly important to understand the mechanisms that contribute to insulin dysregulation. The higher risk for metabolic syndrome imparted by antipsychotic medication use highlights one such mechanism. Though there is great variation in the number and types of signaling pathways targeted by these medications, the one common mechanism of action is through dopamine. Dopamine's effects on insulin signaling begin at the level of insulin secretion from the pancreas and continue through the central nervous system. In a reciprocal fashion, insulin also affects dopamine signaling, with specific effects on dopamine reuptake from the synapse. This review probes the dopamine-insulin connection to provide a comprehensive examination of how antipsychotics may contribute towards insulin resistance.
... your desktop! more... Why Does My Dentist Prescribe Medication? Article Chapters Why Does My Dentist Prescribe Medication? ... dentist or pharmacist. Reviewed: January 2012 Related Articles: Medication Epilepsy, Seizure Meds Have Oral Health Implications How ...
Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan
Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50
Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Sirois, Patricia A; Oleske, James M; Malee, Kathleen; Pearson, Deborah A; Nichols, Sharon L; Garvie, Patricia A; Farley, John; Nozyce, Molly L; Mintz, Mark; Williams, Paige L
Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3-18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1-3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase = 0.192, p = 0.003; long-term increase = 0.350, p < 0.001), and for risperidone alone (short-term = 0.239, p = 0.002; long-term = 0.360, p = 0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection.
Aaron, Lisa; Montepiedra, Grace; Sirois, Patricia A.; Oleske, James M.; Malee, Kathleen; Pearson, Deborah A.; Nichols, Sharon L.; Garvie, Patricia A.; Farley, John; Nozyce, Molly L.; Mintz, Mark; Williams, Paige L.
Abstract Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3–18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1–3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase = 0.192, p = 0.003; long-term increase = 0.350, p < 0.001), and for risperidone alone (short-term = 0.239, p = 0.002; long-term = 0.360, p = 0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection. PMID:19827949
Wyatt, T D; Passmore, C M; Morrow, N C; Reilly, P M
OBJECTIVE--To see whether changes in prescribing of oral antibacterials in Northern Ireland show the need for a community antibiotics policy. DESIGN--Analysis of prescribing totals for several oral antibiotics obtained retrospectively from the prescription pricing bureau for the years 1983-7. SETTING--Audit of anti-infective prescribing in general practice in Northern Ireland over five years. MAIN OUTCOME MEASURE--Respective usage of agents defined as "common" and "occasional" in 1983. RESULTS--There was a gradual decrease in the relative use of common agents from 82% of the total in 1983 to 77% in 1987 together with a complementary increase in the use of occasional agents from 5% to 10%. Pronounced changes were noted in the use of amoxycillin, ampicillin, erythromycin, minocycline, doxycycline, and amoxycillin-clavulanic acid. CONCLUSION--Though this survey found reasonably conservative prescribing, the trend towards increased use of occasional agents has both clinical and cost implications which could be addressed by the use of a prescribing formulary. PMID:2107899
Cotes, Robert O; de Nesnera, Alex; Kelly, Michael; Orsini, Karen; Xie, Haiyi; McHugo, Greg; Bartels, Stephen; Brunette, Mary F
Antipsychotic medications can cause serious cardiometabolic side effects. No recent research has broadly evaluated monitoring and strategies to improve monitoring in U.S. public mental health systems. To address this knowledge gap, we evaluated education with audit and feedback to leaders to improve cardiometabolic monitoring in a state mental health system. We used Chi square statistics and logistic regressions to explore changes in monitoring recorded in randomly sampled records over 2 years. In 2009, assessment of patients on antipsychotics was 29.6 % for cholesterol, 40.4 % for glucose, 29.1 % for triglycerides, 54.3 % for weight, 33.6 % for blood pressure, and 5.7 % for abdominal girth. In 2010, four of ten mental health centers improved their rate of adult laboratory monitoring. Overall monitoring in the state did not increase. Education for prescribers with audit and feedback to leaders can improve monitoring in some settings, but more intensive and/or prolonged interventions may be required.
Song, Woo Seok; Cha, Jin Hee; Yoon, Sang Ho; Cho, Young Seon; Park, Kyeong-Yeol; Kim, Myoung-Hwan
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown. Here we show that Olz interrupts depotentiation (reversal of long-term potentiation) without disturbing de novo LTP (long-term potentiation) and LTD (long-term depression). At hippocampal SC-CA1 synapses, inhibition of NMDARs (N-methyl-d-aspartate receptors), mGluRs (metabotropic glutamate receptors), or mAChRs (muscarinic acetylcholine receptors) disrupted depotentiation. In addition, co-activation of NMDARs, mGluRs, and mAChRs reversed stably expressed LTP. Olz inhibits the activation of mAChRs, which amplifies glutamate signaling through enhanced NMDAR opening and Gq (Gq class of G protein)-mediated signal transduction. Behaviorally, Olz impairs spatial reversal learning of mice in the Morris water maze test. Our results uncover a novel mechanism underpinning the cognitive modulation of Olz and show that the anticholinergic property of Olz affects glutamate signaling and synaptic plasticity.
Perez-Iglesias, Rocio; Mata, Ignacio; Amado, Jose Antonio; Berja, Ana; Garcia-Unzueta, Maria Teresa; Martínez García, Obdulia; Arranz, Maria Jesús; Vazquez-Barquero, Jose Luis; Crespo-Facorro, Benedicto
Weight gain is one of the major adverse effects of antipsychotics. Although mechanisms remain unclear, genetic susceptibility has become increasingly attractive as a potential mechanism that could explain a significant part of interindividual variability. Most investigations have explored genes related with the mechanism of action of antipsychotic drugs. An alternative approach to investigate the role that genetic factors play in weight gain secondary to antipsychotic treatment is to study those genetic variants that have been found associated with obesity. The aim of this study was to determine whether the fat mass and obesity-associated gene (FTO) rs9939609 variant, the single nucleotide polymorphism that has shown the strongest association with common obesity in different populations, influences weight gain during the first year of antipsychotic treatment. We investigated also the genetic variants in other 3 strong candidates genes involved in the leptin-signaling pathway including leptin, leptin receptor, and Src homology 2. We carried out a prospective study on 239 patients with first-episode psychosis. Two hundred five patients completed the follow-up at 1 year (85.8%). Before antipsychotic treatment, the homozygous subjects for the risk allele A of the FTOrs9939609 variant had a higher body mass index at baseline (24.2 T 3.8 kg/m²) than the AT/TT group (22.82 T 3.3 kg/m2; F = 5.744; P = 0.018). After 1 year, the magnitude of weight increase was similar in the 3 genotypes defined by the rs9939609 variant. These results suggest that the pharmacological intervention accompanied by changes in energy intake and expenditure could suppress the genetic susceptibility conferred by the FTO genotype. None of the other single nucleotide polymorphisms evaluated were associated with weight gain during the first 12 months of antipsychotic therapy.
Ye, Wenyu; Ascher-Svanum, Haya; Tanji, Yuka; Flynn, Jennifer A; Takahashi, Michihiro; Conley, Robert R
Purpose Antipsychotic monotherapy is often recommended over antipsychotic polypharmacy because of fewer adverse events, reduced treatment complexity, and lower medication cost. This study compared the rate and the duration of antipsychotic monotherapy following initiation of olanzapine or risperidone in the treatment of outpatients with schizophrenia in Japan. Methods Outpatients diagnosed with schizophrenia in the Japan Medical Data Center database were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, diagnosis codes. Patients were between 20 and 65 years old, initiated on olanzapine or risperidone therapy between August 2003 and July 2008, and continuously enrolled during the 6 months prior to and the 12 months following the initiation date. Antipsychotic polypharmacy was defined as concurrent use of two or more antipsychotics. The probability of monotherapy during the 12-month follow-up period was assessed using a propensity score-adjusted generalized estimating equation model. Duration of monotherapy was contrasted using a propensity score-adjusted bootstrapping model. Results After applying all inclusion and exclusion criteria, the final analytic sample consisted of 332 olanzapine- and 496 risperidone-treated outpatients. At treatment initiation, 61.5% of the olanzapine-treated patients and 45.6% of the risperidone-treated patients received antipsychotic monotherapy (P < 0.001). After correcting for background differences, monotherapy was more common among olanzapine-treated patients (P = 0.001). In addition, olanzapine was used as monotherapy for a longer duration (P = 0.006). Conclusion Consistent with prior global research, this retrospective naturalistic study of schizophrenia outpatients in Japan found that olanzapine is more likely to be used as monotherapy and to be used as monotherapy for a longer duration than risperidone. PMID:22745559
Zuo, Silu; Fries, Brant E.; Szafara, Kristina; Regal, Randolph
Background: Valproic acid (VPA) is one of the most commonly used antiepileptic medications worldwide; it is also a popular mood stabilizer for use in bipolar disorder and dementia. This study assessed whether VPA may potentiate metabolic side effects in patients with psychiatric disorders taking concomitant antipsychotics (APs). VPA alone has been associated with weight gain, dyslipidemia, hypertension, and diabetes. Patients with psychiatric disorders, especially those on second-generation (atypical) APs, appear to be at increased risk of these metabolic effects. A secondary purpose was to determine if a linear dose–response relationship exists between the VPA dose and adverse metabolic effects. Methods: This cross-sectional study was conducted using data collected on all patients in the four state-operated psychiatric hospitals in Michigan using a comprehensive assessment instrument, the interRAI Mental Health. All patients taking both VPA and APs (n = 200) were compared to a control group of patients taking APs without VPA (n = 426). Patients were assessed for the presence of the following surrogate indicators of metabolic syndrome: weight gain; high body mass index (BMI greater than 30 kg/m2); very high BMI (BMI greater than 40 kg/m2); a diagnosis of diabetes mellitus; use of a prescribed statin medication; diagnosis of hyperlipidemia or dyslipidemia; hypertension; or the combination of any three of these factors: high BMI, hyperlipidemia or dyslipidemia, diabetes, and hypertension. Analysis also included assessment of the effect of VPA dosage on metabolic side effects. Results: Patients in the VPA plus APs group were 3.2 kg heavier than those in the APs group (P = 0.05) at baseline. Compared with the APs group, the VPA plus APs group had a higher prevalence of high and very high BMI, diabetes, hypertension, and the combination of any three factors of high BMI, hyperlipidemia/dyslipidemia, diabetes, and hypertension. However, these differences were not
Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318
Sun, Jingchun; Xu, Hua; Zhao, Zhongming
Antipsychotic drugs are tranquilizing psychiatric medications primarily used in the treatment of schizophrenia and similar severe mental disorders. So far, most of these drugs have been discovered without knowing much on the molecular mechanisms of their actions. The available large amount of pharmacogenetics, pharmacometabolomics, and pharmacoproteomics data for many drugs makes it possible to systematically explore the molecular mechanisms underlying drug actions. In this study, we applied a unique network-based approach to investigate antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs, 42 unique target genes, and 46 adverse drug interactions from the DrugBank database and then generated a drug-gene network and a drug-drug interaction network. Through drug-gene network analysis, we found that seven atypical antipsychotic drugs tended to form two clusters that could be defined by drugs with different target receptor profiles. In the drug-drug interaction network, we found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to have more adverse drug interactions than others, while clozapine had fewer adverse drug interactions. This investigation indicated that these antipsychotics might have different molecular mechanisms underlying the drug actions. This pilot network-assisted investigation of antipsychotics demonstrates that network-based analysis is useful for uncovering the molecular actions of antipsychotics.
Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy
Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.
Efron, Nathan; Morgan, Philip B; Helland, Magne; Itoi, Motozumi; Jones, Deborah; Nichols, Jason J; van der Worp, Eef; Woods, Craig A
Rigid lenses have been fitted less since the introduction of soft lenses nearly 40 years ago. Data that we have gathered from annual contact lens fitting surveys conducted in Australia, Canada, Japan, the Netherlands, Norway, the UK and the USA between 2000 and 2008 facilitate an accurate characterization of the pattern of the decline of rigid lens fitting during the first decade of this century. There is a trend for rigid lenses to be utilized primarily for refitting those patients who are already successful rigid lens wearers-most typically older females being refit with higher Dk materials. Rigid lenses are generally fitted on a full-time basis (four or more days of wear per week) without a planned replacement schedule. Orthokeratology is especially popular in the Netherlands, but is seldom prescribed in the other countries surveyed.
Price, Scott A.; Brahm, Nancy C.
BACKGROUND A diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients. METHODS A review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms “addiction,” “adolescence,” “childhood,” “dual diagnosis,” “schizophrenia,” and “substance abuse.” Results were limited to English-language articles. RESULTS Seven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events. CONCLUSION There is a great need for
Lake, Stephanie; Kerr, Thomas; Montaner, Julio
There has been much recent discussion and debate surrounding cannabis in Canada, including the prescribing of medical cannabis for therapeutic purposes. Certain commentators - including the Canadian Medical Association (CMA) - have denounced the prescribing of cannabis for medical purposes due to a perceived lack of evidence related to the drug's efficacy, harms, and mechanism of action. In this commentary, we present arguments in favour of prescribing medical cannabis in Canada. We believe the anti-cannabis position taken by CMA and other commentators is not entirely evidence-based. Using the example of neuropathic pain, we present and summarize the clinical evidence surrounding smoked or vapourized cannabis, including recent evidence pertaining to the effectiveness of cannabis in comparison to existing standard pharmacotherapies for neuropathy. Further, we outline how the concerns expressed regarding cannabis' mechanism of action are inconsistent with current decision-making processes related to the prescribing of many common pharmaceuticals. Finally, we discuss potential secondary public health benefits of prescribing cannabis for pain-related disorders in Canada and North America.
Nazar, Hamde; Nazar, Mahdi; Rothwell, Charlotte; Portlock, Jane; Chaytor, Andrew; Husband, Andrew
Prescribing is a characteristic role of a medical practitioner. On graduating from medical school, students are presumed to have acquired the necessary pharmacology knowledge underpinning the therapeutics and developed their personal skills and behaviors in order to write a safe and effective prescription (The Four Ps). However, there are reports of errors in medical prescribing and dissatisfied feedback from recent graduates, which evidence potential flaws in the current training in the practice of prescribing. We examine the Four Ps from a systems approach and offer scope for educators and curriculum designers to review and reflect on their current undergraduate teaching, learning, and assessment strategies in a similar manner. We also adopt a national framework of common competencies required of all prescribers to remain effective and safe in their area of practice as a more objective layer to the broader learning outcomes of the General Medical Council Tomorrow’s Doctors 2009. This exercise demonstrates where standard, recognized competencies for safe prescribing can be accommodated pedagogically within existing medical curricula. PMID:25945072
Sicouri, Serge; Antzelevitch, Charles
A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use.
Bushe, Chris; Shaw, Michael; Peveler, Robert C
Recent evidence linking hyperprolactinaemia to longer-term clinical sequelae, including osteoporosis, hip fractures and possibly breast cancer, is increasing clinical awareness of the relevance of hyperprolactinaemia. A review of the literature finds clinical trials reporting some degree of comparative prolactin data among antipsychotics. Many of the randomised clinical trials (RCTs) do not report categorical rates of hyperprolactinaemia in contrast with the naturalistic studies, making it complex for clinicians to evaluate the extent and severity of hyperprolactinaemia. Hyperprolactinaemia is one of the commonest adverse events reported in clinical trials and can be found in association with all antipsychotics. The highest rates of hyperprolactinaemia are reported in association with risperidone and amisulpride, often as high as 80-90% of all female subjects and consistently greater than with the typical antipsychotics. Significant rates of hyperprolactinaemia of lesser severity and more transience have also been reported in association with other atypical antipsychotics.
West, Joyce C.; Marcus, Steven C.; Wilk, Joshua; Countis, Lisa M.; Regier, Darrel A.; Olfson, Mark
Objectives: To describe factors associated with initiation of depot antipsychotic medications in psychiatric outpatients with schizophrenia and recent medication nonadherence. Methods: A national sample of psychiatrists reported on adult outpatients with schizophrenia who were nonadherent with oral antipsychotic medications in the last year. Results: In total, 17.6% of psychiatrists initiated depot antipsychotic injections. Initiation was significantly and positively associated with public insurance, prior inpatient admission, proportion of time nonadherent, average or above average intellectual functioning, and living in a mental health residence. Use was inversely associated with using second-generation antipsychotics and other oral psychotropic medications prior to medication nonadherence. Psychiatrists who were male, nonwhite, and more optimistic about managing nonadherence were more likely to initiate depot injections. Conclusions: Initiation of depot injections is a joint function of patient, physician, treatment, and setting factors. Use of long-acting preparations in this population is uncommon despite clinical recommendations urging their use. PMID:18093962
Lertxundi, Unax; Domingo-Echaburu, Saioa; Peral, Javier; García, Montserrat
Published literature shows that dopamine agonists can reverse antipsychotic-induced hyperprolactinemia without worsening psychotic symptoms in the majority of schizophrenic patients. However, psychiatrists have been reluctant to use drugs with dopaminergic properties for fear of exacerbating psychiatric symptoms. There are reported cases of psychosis worsening published for both cabergoline and bromocriptine. Cabergoline has proven to be more effective and safe when used to treat hyperprolactinemia, but whether cabergoline is also safer than bromocriptine in antipsychotic induced hyperprolactinemia remains unproven.
Lertxundi, Unax; Domingo-Echaburu, Saioa; Peral, Javier; García, Montserrat
Published literature shows that dopamine agonists can reverse antipsychotic-induced hyperprolactinemia without worsening psychotic symptoms in the majority of schizophrenic patients. However, psychiatrists have been reluctant to use drugs with dopaminergic properties for fear of exacerbating psychiatric symptoms. There are reported cases of psychosis worsening published for both cabergoline and bromocriptine. Cabergoline has proven to be more effective and safe when used to treat hyperprolactinemia, but whether cabergoline is also safer than bromocriptine in antipsychotic induced hyperprolactinemia remains unproven. PMID:27738363
Aston, Jacqueline; Rechsteiner, Evelyne; Bull, Nadine; Borgwardt, Stefan; Gschwandtner, Ute; Riecher-Rössler, Anita
Hyperprolactinaemia is often found in patients with schizophrenia and usually considered a consequence of antipsychotics. Prolactin levels were measured in 43 At-Risk Mental State individuals (ARMS) and 26 patients with First Episode Psychosis (FEP). Hyperprolactinaemia was found in 25.6% of ARMS and 46.2% of FEP. Within 60 antipsychotic-naïve ARMS and FEP, hyperprolactinaemia was found in 26.7%. Hyperprolactinaemia may be pre-existing in a subgroup of patients with schizophrenia.
Lenderts, Susan; Kalali, Amir H; Buckley, Peter
In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.
Kay, C R
Guidelines for prescribing oral contraceptives (Ocs), which take into account recent research findings concerning the relationship between OC use and the development of cervical and breast neoplasia and vascular diseases, were suggested. The findings of M.P. Vessey and his colleagues that the risk of cervical neoplasia increases with the duration of OC use are difficult to interpret. OC is strongly associated with certain types of sexual behavior, e.g., initiation of sexual activity at an early age, frequent intercourse, and intercourse with multiple partners, and these behavioral factors, in turn, are known to be associated with an increased risk of cervical cancer. Although an attempt was made to control for the effects of these behavioral factors, the findings of the study require further substantiation. Even if the findings are correct, OC users would appear to have only a minor excess risk of developing invasive carcinoma, and even this minimal increased risk could be avoided encouraging OC users to have cervical smears taken routinely. The findings of Pike and his colleagues in California concerning the risk of breast cancer among OC users are more controversial, and potentially more serious. The study found that there was a 4-fold increased risk of breast cancer in women, under the age of 37, who had used OCs prior to their 25th birthday, and the risk increased with duration of OC use. A study by McPerson and colleagues also reported that breast cancer was associated with the duration of OC use prior to 1st pregnancy. Other intensive studies have failed to reveal a relationship between breast neoplasia and OC use. Pike and his colleagues also published a table listing OC brands in rank order of their progestogen potency. Pike noted that there was a positive relationship between the occurrence of breast cancer and the level of progestogen potency. The table was harshly criticized because it is not possible to determine the potency level of combined
Thinning and prescribed fire are common management tools used to eliminate thick fuel loads that could otherwise facilitate and encourage a more severe catastrophic wildfire. The objective of this study was to quantify the lasting effects of prescribed fire on forest floor and soil nutrients approxi...
Zuardi, A W; Crippa, J A S; Hallak, J E C; Moreira, F A; Guimarães, F S
A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis) component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD), a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.
Seeman, Mary V.
Context: The health burden of antipsychotic medication is well known, but the disproportionate effect on women as compared with men is underappreciated. Objective: The goal of this article is preventive—to better inform clinicians so that the risks to women and to their offspring can be diminished. Method: All PubMed sources in which the search term gender (or sex) was linked to a side effect of antipsychotic medication were reviewed. Result: There is general agreement in the literature on women's increased susceptibility to weight gain, diabetes, and specific cardiovascular risks of antipsychotics, with less consensus on malignancy risks and risks to the fetus. Cardiovascular death, to which men are more susceptible than women, is disproportionately increased in women by the use of antipsychotics. Sedating antipsychotics raise the risk of embolic phenomena during pregnancy, and postpartum. Prolactin-elevating drugs suppress gonadal hormone secretion and may enhance autoimmune proclivity. Conclusions: Clinicians need to be aware of the differential harm that women (and their offspring) can incur from the side effects of antipsychotics. PMID:18400811
Miller, Del D.; Caroff, Stanley N.; Davis, Sonia M.; Rosenheck, Robert A.; McEvoy, Joseph P.; Saltz, Bruce L.; Riggio, Silvana; Chakos, Miranda H.; Swartz, Marvin S.; Keefe, Richard S. E.; Stroup, T. Scott; Lieberman, Jeffrey A.
Background There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. Aims To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia. Method Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. Results There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine. Conclusions The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia. PMID:18827289
Bushe, Chris; Yeomans, David; Floyd, Tamsin; Smith, Shubulade M
Hyperprolactinaemia may be associated with hidden longer-term consequences, such as osteoporosis, bone fractures, pituitary tumours and breast cancer. Prolactin data from clinical trials is not always reported in a categorical manner and does not always allow the risk of hyperprolactinaemia to be evaluated for specific patient cohorts. Patients participating in a physical health management programme in the UK for severe mental illness patients--the Well-being Support Programme--had prolactin measurements made regardless of symptoms. Prolactin data from the complete cohort of 178 patients receiving antipsychotics in Leeds and London are reported. Hyperprolactinaemia was measured in 33.1% but more commonly in females than males (47.3% and 17.6%) and was associated with all antipsychotics except clozapine. The highest prevalence rates were found in amisulpride (n=20) 89%, risperidone long-acting intramuscular injection (LAIM) 67% (n=6) and risperidone (n=30) 55% used as antipsychotic monotherapy. Clinically Significant hyperprolactinaemia (>1000 mIU/L approximately 47 ng/ml) was measured in 15.8% of patients, predominantly in females. Levels >2000 mIU/L approximately 95 ng/ml in 6.2% of the complete cohort. Clinicians may wish to add prolactin measurement to the routine laboratory parameters currently measured for some antipsychotics and should be advised of the potential longer-term consequences of hidden hyperprolactinaemia.
Dar-Odeh, Najla Saeed; Abu-Hammad, Osama Abdalla; Al-Omiri, Mahmoud Khaled; Khraisat, Ameen Sameh; Shehabi, Asem Ata
Antibiotics are prescribed by dentists for treatment as well as prevention of infection. Indications for the use of systemic antibiotics in dentistry are limited, since most dental and periodontal diseases are best managed by operative intervention and oral hygiene measures. However, the literature provides evidence of inadequate prescribing practices by dentists, due to a number of factors ranging from inadequate knowledge to social factors. Here we review studies that investigated the pattern of antibiotic use by dentists worldwide. The main defects in the knowledge of antibiotic prescribing are outlined. The main conclusion is that, unfortunately, the prescribing practices of dentists are inadequate and this is manifested by over-prescribing. Recommendations to improve antibiotic prescribing practices are presented in an attempt to curb the increasing incidence of antibiotic resistance and other side effects of antibiotic abuse. PMID:20668712
Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan
Background In many countries of the industrialised world second generation (“atypical”) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Main results The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole
Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan
Background Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. Objectives To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. Selection criteria All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. Data collection and analysis We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. Main results The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation
Burghardt, Kyle J.; Evans, Simon J.; Wiese, Kristen M.; Ellingrod, Vicki L.
Background Second generation antipsychotic (SGA) use in bipolar disorder is common and has proven effective in short-term trials. There continues to be a lack of understanding of the mechanisms underlying many of their positive and negative effects in bipolar disorder. This study aimed to describe the metabolite profiles of bipolar subjects treated with SGAs by comparing to metabolite profiles of bipolar subjects treated with lithium, and schizophrenia subjects treated with SGAs. Methods Cross-sectional, fasting untargeted serum metabolomic profiling was conducted in 82 subjects diagnosed with bipolar I disorder (n=30 on SGAs and n=32 on lithium) or schizophrenia (n=20). Metabolomic profiles of bipolar subjects treated with SGAs were compared to bipolar subjects treated with lithium and schizophrenia subjects treated with SGAs using multivariate methods. Results Partial lease square discriminant analysis (PLS-DA) plots showed separation between bipolar subjects treated with SGAs, bipolar subjects treated with lithium, or schizophrenia subjects treated with SGAs. Top influential metabolite features were associated with several pathways including that of polyunsaturated fatty acids, pyruvate, glucose and branched chain amino acids. Conclusions The findings from this study require further validation in pre and post treated bipolar and schizophrenia subjects, but suggest that the pharmacometabolome may be diagnosis specific. PMID:26314700
Menard, Marie-Line; Thümmler, Susanne; Giannitelli, Marianna; Olliac, Bertrand; Bonnot, Olivier; Cohen, David; Askenazy, Florence
Introduction In France, over recent years, the prescription rate of antipsychotic (AP) remained stable in children and adolescents. Prescription of second-generation antipsychotics increased, whereas prescription of first-generation antipsychotics decreased. Off-label prescriptions are very frequent in this population. Adverse events (AEs) in youth treated with AP are common and may be severe. AEs have hitherto been poorly monitored in naturalistic studies independent from industry. Method and analysis We describe a French prospective multicentre study in an AP-naïve paediatric population named Etude de la Tolérance des AntiPsychotique chez l'Enfant (ETAPE). The study started in April 2013. So far, 200 patients have been included. The inclusion criteria are: male or female inpatients aged from 6 to 18 years, treated with an AP drug for less than 28 days, never been treated or having received AP for less than 3 months, discontinued at least 6 months prior to inclusion. These assessments of AE are performed at inclusion, as well as at 3, 6, 9 and 12 months after the introduction of the AP. The monitoring period will end in May 2016. Ethics and dissemination The study protocol was approved by the Ethics Committee ‘Sud Méditerrané V’ (number 12.082) and by the French National Agency for Medicines and Health Products Safety (number 2012-004546-15). All patients and their parents signed informed consent on enrolment in the study. We will submit the results of the study to relevant journals and offer national and international presentations. This study will enable better characterisation of the prescription of AP drugs. The results will further help to develop quality standards and recommendations for monitoring AE during the prescription of AP. Trial registration number NCT02007928. PMID:27053275
Outcome of Youth with Early-Phase Schizophrenia-Spectrum Disorders and Psychosis Not Otherwise Specified Treated with Second-Generation Antipsychotics: 12 Week Results from a Prospective, Naturalistic Cohort Study
Vernal, Ditte L.; Kapoor, Sandeep; Al-Jadiri, Aseel; Sheridan, Eva M.; Borenstein, Yehonathan; Mormando, Charles; David, Lisa; Singh, Sukhbir; Seidman, Andrew J.; Carbon, Maren; Gerstenberg, Miriam; Saito, Ema; Kane, John M.; Steinhausen, Hans-Christoph
Abstract Objectives: The purpose of this study was to assess differences in the outcomes of youth with schizophrenia-spectrum disorders (SCZ-S) and psychotic disorder not otherwise specified (PsyNOS) during early antipsychotic treatment. Methods: The study was a prospective, naturalistic, inception cohort study of youth ≤19 years old with SCZ-S (schizophrenia, schizoaffective disorder, schizophreniform disorder) or PsyNOS (PsyNOS, brief psychotic disorder) and ≤24 months of lifetime antipsychotic treatment receiving clinician's choice antipsychotic treatment. Baseline demographic, illness and treatment variables, and effectiveness outcomes were compared at 12 weeks last-observation-carried-forward across SCZ-S and PsyNOS patients, adjusting for significantly different baseline variables. Results: Altogether, 130 youth with SCZ-S (n=42) or PsyNOS (n=88), mostly antipsychotic naïve (76.9%), were prescribed risperidone (47.7%), olanzapine (19.2%), aripiprazole (14.6%), quetiapine (11.5%), or ziprasidone (6.9%). Compared with those with PsyNOS, SCZ-S youth were older (16.4±2.1 vs. 14.8±3.2, p=0.0040), and less likely to be Caucasian (19.1% vs. 42.5%, p=0.009). At baseline, SCZ-S patients had significantly higher Clinical Global Impressions-Severity (CGI-S) scores (6.0±0.9 vs. 5.5±0.8, p=0.0018) and lower Children's Global Assessment Scale (CGAS) scores (29.6±9.2 vs. 36.1±8.9, p=0.0002) and were more likely to be in the severely ill CGAS group (i.e., CGAS≤40). SCZ-S and PsyNOS patients did not differ regarding all-cause discontinuation (40.5 vs. 40.3%. p=0.49), discontinuation because of adverse effects (12.2% vs. 12.4%, p=0.97), or nonadherence (29.3% vs. 30.9%, p=0.88), but somewhat more SCZ-S patients discontinued treatment for inefficacy (19.5% vs. 7.4%, p=0.063). CGI-S and CGAS scores improved significantly in both diagnostic groups (p=0.0001, each). Adjusting for baseline differences, PsyNOS patients experienced significantly better CGI-I improvement
Kishimoto, Taishiro; Sanghani, Sohag; Russ, Mark J; Marsh, Akeem N; Morris, Joshua; Basu, Suparna; John, Majnu; Kane, John M
Studies have examined the differences in sociodemographic/clinical characteristics between patients on long-acting injectable (LAI) versus oral medications. However, most studies did not focus specifically on patients for whom LAIs would clearly be indicated. We performed a chart review of patients with schizophrenia or schizoaffective disorder. Patients were categorized as having an 'indication for an LAI' or not on the basis of their adherence history. Patients for whom an LAI was indicated and prescribed on discharge were then compared with similar patients for whom an LAI was not prescribed. Of 305 charts reviewed, consisting of 279 unique patients, 27.2% were judged to have an indication for an LAI (n=76), but only 32.9% of these (n=25) were discharged on an LAI. In the multiregression model, being African American, residing in a psychiatric residence, having a previous history of an LAI trial, and being treated with a higher antipsychotic dose were predictive of LAI prescription. It is important to focus on the population who are not likely to receive an LAI, but who have such indications for treatment.
Masand, Prakash S.
Behavioral disturbances and psychosis are common features of neurodegenerative disorders and may be drug induced, intrinsic to the underlying pathology, or both. These disturbances, including psychotic and mood symptoms, apathy, aggression and other behavioral symptoms, and superimposed delirium, cause a great amount of disability to the patient and stress on the caregiver. Conventional neuroleptics have been shown to be effective in the treatment of these symptoms, but unacceptable side effects may occur. However, the novel antipsychotics, with their lower risk of inducing extrapyramidal symptoms, have shown promise in the treatment of behavioral disturbances and psychosis associated with neurodegenerative disorders. PMID:15014653
Baptista, Trino; ElFakih, Yamily; Uzcátegui, Euderruh; Sandia, Ignacio; Tálamo, Eduardo; Araujo de Baptista, Enma; Beaulieu, Serge
Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.
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Greenbaum, Lior; Lerer, Bernard
Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson's disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.
Lin, Liang; Teng, Monica; Khoo, Ai Leng; Soh, Lay Beng; Furukawa, Toshiaki A.; Baldessarini, Ross J.; Lim, Boon Peng; Sim, Kang
Background For treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review. Aims To evaluate the comparative long-term effectiveness of antipsychotic drugs. Method We systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo. Results Studies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4–156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents. Conclusions Except for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders. Declaration of interest R.J.B. received grants from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703755
... Under-Prescribing Flu Antiviral Drugs and Possibly Overprescribing Antibiotics Language: English EspaÃ±ol Recommend on Facebook Tweet ... medications. In contrast, clinicians may have overprescribed common antibiotics. The authors of the study concluded that more ...
Chitty, Kate M; Dobbins, Timothy; Dawson, Andrew H; Isbister, Geoffrey K; Buckley, Nicholas A
BackgroundAcute alcohol consumption is a major risk factor for suicide, therefore investigating factors associated with alcohol-related self-harm warrant attention.AimsTo investigate the influence of prescribed psychotropic medications on the odds of co-ingesting alcohol preceding or during intentional efforts to self-poison.MethodA cross-sectional analysis of consecutive hospital presentations following intentional self-poisoning was conducted. A total of 7270 patients (4363 women) aged 18-96 were included.ResultsThe odds of alcohol co-ingestion were increased in those not prescribed any medication (odds ratio (OR) = 1.27, 99% CI 1.10-1.46, P<0.001) and in impulsive self-poisonings (OR = 1.39, 99% CI 1.11-1.74, P<0.001). Odds were decreased in those prescribed anticonvulsants (OR = 0.69, 99% CI 0.51-0.93), antipsychotics (OR = 0.55, 99% CI 0.45-0.66) and antidepressants (OR = 0.87, 99% CI 0.77-0.99).ConclusionsFindings indicate that being medicated for a psychiatric illness may reduce the likelihood of alcohol consumption during times of acute distress, hence perhaps may reduce the risk of intentional self-poisoning.
Shea, Michael; Fields, Karl B.
Plantar fasciitis is an extremely common, painful injury seen among people in running and jumping sports. While prognosis for recovery with conservative care is excellent, prolonged duration of symptoms affects sports participation. Studies on treatment options show mixed results, so finding effective treatments can be challenging. A logical…
Whiskey, Eromona; Taylor, David
Introduction. The objective of this study was to develop a decision aid that patients and clinicians might use to help the patient in the process of selecting an antipsychotic medication. In addition, we aimed to determine the antipsychotic that patients would choose given the information contained in the leaflet. Method. We designed a questionnaire for patients to appraise the contents of the leaflet, their understanding of the leaflet and the potential impact of the leaflet on compliance and therapeutic relationship between patient and doctor. Results. We recruited 30 stable patients with a diagnosis of a psychotic illness to evaluate the leaflet and to determine patient choice. Over 90% of patients felt that the leaflet improved their knowledge of antipsychotic medication. Seventy-six percent of patients agreed that the leaflet contained the right type and amount of information. Seventy percent of respondents believed the leaflet would improve the trust between them and their doctors, and almost half (47%) stated they were more likely to take their medicine after reading the leaflet. Forty percent of patients would prefer to switch antipsychotic medication, with quetiapine being the most frequently preferred option. Conclusion. The results indicate that, for patients in the stable phase of their illness, the leaflet is a useful tool in selecting an antipsychotic medication and may represent a way forward in improving outcomes in patients with psychotic disorders. A larger study examining outcomes using this tool would establish its clinical utility.
Barbui, Corrado; Bighelli, Irene; Carrà, Giuseppe; Castellazzi, Mariasole; Lucii, Claudio; Martinotti, Giovanni; Nosè, Michela; Ostuzzi, Giovanni
Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = −12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = −2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy. PMID:26840602
Vodicka, Talley A; Thompson, Matthew; Lucas, Patricia; Heneghan, Carl; Blair, Peter S; Buckley, David I; Redmond, Niamh; Hay, Alastair D
Background Respiratory tract infections (RTIs) in children are common and often result in antibiotic prescription despite their typically self-limiting course. Aim To assess the effectiveness of primary care based interventions to reduce antibiotic prescribing for children with RTIs. Design and setting Systematic review. Method MEDLINE®, Embase, CINAHL®, PsycINFO, and the Cochrane library were searched for randomised, cluster randomised, and non-randomised studies testing educational and/or behavioural interventions to change antibiotic prescribing for children (<18 years) with RTIs. Main outcomes included change in proportion of total antibiotic prescribing or change in ‘appropriate’ prescribing for RTIs. Narrative analysis of included studies was used to identify components of effective interventions. Results Of 6301 references identified through database searching, 17 studies were included. Interventions that combined parent education with clinician behaviour change decreased antibiotic prescribing rates by between 6–21%; structuring the parent–clinician interaction during the consultation may further increase the effectiveness of these interventions. Automatic computerised prescribing prompts increased prescribing appropriateness, while passive information, in the form of waiting room educational materials, yielded no benefit. Conclusion Conflicting evidence from the included studies found that interventions directed towards parents and/or clinicians can reduce rates of antibiotic prescribing. The most effective interventions target both parents and clinicians during consultations, provide automatic prescribing prompts, and promote clinician leadership in the intervention design. PMID:23834881
Arad, Michal; Weiner, Ina
The estrogen hypothesis of schizophrenia suggests that estrogen is a natural neuroprotector in women and that exogenous estrogen may have antipsychotic potential, but results of clinical studies have been inconsistent. We have recently shown using the latent inhibition (LI) model of schizophrenia that 17β-estradiol exerts antipsychotic activity in ovariectomized (OVX) rats. The present study sought to extend the characterization of the antipsychotic action of 17β-estradiol (10, 50 and 150 μg/kg) by testing its capacity to reverse amphetamine- and MK-801-induced LI aberrations in gonadally intact female and male rats. No-drug controls of both sexes showed LI, ie, reduced efficacy of a previously non-reinforced stimulus to gain behavioral control when paired with reinforcement, if conditioned with two but not five tone-shock pairings. In both sexes, amphetamine (1 mg/kg) and MK-801 (50 μg/kg) produced disruption (under weak conditioning) and persistence (under strong conditioning) of LI, modeling positive and negative/cognitive symptoms, respectively. 17β-estradiol at 50 and 150 μg/kg potentiated LI under strong conditioning and reversed amphetamine-induced LI disruption in both males and females, mimicking the action of typical and atypical antipsychotic drugs (APDs) in the LI model. 17β-estradiol also reversed MK-induced persistent LI, an effect mimicking atypical APDs and NMDA receptor enhancers, but this effect was observed in males and OVX females but not in intact females. These findings indicate that in the LI model, 17β-estradiol exerts a clear-cut antipsychotic activity in both sexes and, remarkably, is more efficacious in males and OVX females where it also exerts activity considered predictive of anti-negative/cognitive symptoms.
... html Antipsychotic Drugs May Up Risk of Early Death in Alzheimer's Patients Increased odds were nearly doubled ... antipsychotic drugs significantly increases the risk of premature death among Alzheimer's patients, a new study indicates. Researchers ...
Auta, Asa; Strickland-Hodge, Barry; Maz, Julia
Background In Nigeria, only medical doctors, dentists and some nurses in primary care facilities have the legal right to prescribe medicines to patients. Patients' access to prescription medicines can be seriously affected by the shortage of prescribers leading to longer waiting times in hospitals. Objective This research was carried out to investigate stakeholders' views on granting prescribing authority to pharmacists in Nigeria. Setting The study was conducted in Nigeria. Methods Qualitative, semi-structured interviews were conducted with 43 Nigerian stakeholders including policymakers, pharmacists, doctors and patient group representatives. Transcribed interviews were entered into the QSR NVivo 10 software and analysed using a thematic approach. Main outcome measure Stakeholders' perception on the granting of prescribing authority to pharmacists in Nigeria. Results Three major themes emerged from the interviews: (1) prescribing as a logical role for pharmacists, (2) pharmacist prescribing- an opportunity or a threat and (3) the potential barriers to pharmacist prescribing. Many non-medical stakeholders including pharmacists and patient group representatives supported an extended role for pharmacists in prescribing while the majority of medical doctors including those in policy making were reluctant to do so. Generally, all stakeholders perceived that pharmacist prescribing represents an opportunity to increase patients' access to medicines, reduce doctors' workload and promote the utilisation of pharmacists' skills. However, many stakeholders including pharmacists and doctors commonly identified pharmacists' inadequate skills in diagnosis, medical resistance and shortage of pharmacists as potential barriers to the introduction of pharmacist prescribing in Nigeria. Conclusion The present study showed a split of opinion between participants who were medical doctors and those who were non-doctors in their support for pharmacist prescribing. However, all
Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan
Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with
Background No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes. Methods Patients ≥ 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years. Results A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups. Conclusions Quetiapine appears
Carbon, Maren; Correll, Christoph U
The search for clinical outcome predictors for schizophrenia is as old as the field of psychiatry. However, despite a wealth of large, longitudinal studies into prognostic factors, only very few clinically useful outcome predictors have been identified. The goal of future treatment is to either affect modifiable risk factors, or use nonmodifiable factors to parse patients into therapeutically meaningful subgroups. Most clinical outcome predictors are nonspecific and/or nonmodifiable. Nonmodifiable predictors for poor odds of remission include male sex, younger age at disease onset, poor premorbid adjustment, and severe baseline psychopathology. Modifiable risk factors for poor therapeutic outcomes that clinicians can act upon include longer duration of untreated illness, nonadherence to antipsychotics, comorbidities (especially substance-use disorders), lack of early antipsychotic response, and lack of improvement with non-clozapine antipsychotics, predicting clozapine response. It is hoped that this limited capacity for prediction will improve as pathophysiological understanding increases and/or new treatments for specific aspects of schizophrenia become available.
Cutler, N R
In clinical trials of dopamine-blocking antipsychotics, significant adverse events may occur in healthy volunteers at dose levels that are well tolerated by schizophrenic patients. Because of these differences in tolerability, bioequivalence and pharmacokinetic studies of antipsychotics should be performed in schizophrenic patients rather than in healthy volunteers. When clozapine is the drug being investigated, pharmacokinetic and bioequivalence studies should be carried out in real-life dosage conditions because the half-life of clozapine increases with multiple doses. Under real-life conditions, the evaluation of multiple doses of clozapine in a population of schizophrenic patients can provide direct therapeutic relevance to bioavailability findings. This article discusses patient recruitment and informed consent in pharmacokinetic trials of schizophrenia, issues in studying antipsychotic agents in healthy volunteers versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic patients.
The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within the ventral striatum. The monetary incentive delay (MID) task can be used to study the response of the ventral striatum to incentive stimuli. We show that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics. Switching from first-(typical) to second-generation (atypical) antipsychotics increased activation of the ventral striatum due to less blocking of dopamine D2 receptors. This and similar studies show that functional magnetic resonance imaging (fMRI) tasks are suitable to investigate important aspects of antipsychotic mechanisms.
Gardos, G; Cole, J O
The serious long-term complications of maintenance antipsychotic therapy led the authors to undertake a critical review of outpatient withdrawal studies. Key findings included the following: 1) for a least 40% of outpatient schizophrenics, drugs seem to be essential for survival in the community; 2) the majority of patients who relapse after drug withdrawal recompensate fairly rapidly upon reinstitution of antipsychotic drug therapy; 3) placebo survivors seem to function as well as drug survivors--thus the benefit of maintenance drug therapy appears to be prevention of relapse; and 4) some cases of early relapse after drug withdrawal may be due to dyskinesia rather than psychotic decompensation. The authors urge clinicians to evaluate each patient on maintenance antipsychotic therapy in terms of feasibility of drug withdrawal and offer practical guidelines for withdrawal and subsequent management.
Montgomery, William; Liu, Li; Stensland, Michael D; Xue, Hai Bo; Treuer, Tamas; Ascher-Svanum, Haya
Background This article describes the personal, societal, and economic burden attributable to schizophrenia in the People’s Republic of China and highlights the potential for effective outpatient treatment to reduce this burden given recent changes in the Chinese health care system. The importance of effective antipsychotic therapy in reducing the burden of schizophrenia is also examined. Methods Published research on the burden, disability, management, and economic costs of schizophrenia in the People’s Republic of China was examined in the context of the larger body of global research. Research written in English or Chinese and published before June 2012 was identified using PubMed, CNKI, and Wanfang Med database searches. The contribution of effective antipsychotic therapy in reducing the risk for relapse and hospitalization and improving patients’ functioning is described. Results Schizophrenia imposes a substantial burden on Chinese society, with indirect costs accounting for the majority of the total cost. Functional impairment is high, leading to lost wages and work impairment. In the People’s Republic of China, schizophrenia is the most common diagnosis among hospitalized psychiatric patients. Ongoing changes in the Chinese health care system may reduce some barriers to effective relapse prevention in schizophrenia and potentially reduce hospitalizations. The use of antipsychotics for acute episodes and maintenance treatment has been shown to decrease symptom severity and reduce the risk for relapse and hospitalization. However, discontinuing antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People’s Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment. Conclusion Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People’s Republic of China and globally. When treated
Sneider, Benjamin; Pristed, Sofie Gry; Correll, Christoph U; Nielsen, Jimmi
Although evidence for efficacy of antipsychotic polypharmacy (APP) is sparse, APP is common in schizophrenia. The national Danish health registers were accessed to examine in schizophrenia patients: (1) cross-sectional prevalences of APP (1996-2012); (2) geographic variations in APP (2012); and (3) correlates of APP (2012). APP increased from 17.2% in 1996 to 30.8% in 2006 (p<0.001), declining to 24.6% in 2012 (p<0.001) (overall trend 1996-2012: α=0.653, 95% confidence interval (CI):0.327-0.979, p<0.001). Comparing the 1996-2005 and 2006-2012 cohorts APP occurred significantly faster in the 2006 cohort after schizophrenia diagnosis (p<0.0001). The predominant APP type changed from first-generation antipsychotic combinations in 1996 (77.3%) to first+second-generation antipsychotic combinations in 2003 (70.3%) and second-generation antipsychotic combinations in 2012 (59.2%). In 2012, the prevalence of APP varied from 19.4% in Copenhagen to 29.3% in the region of Zealand. Independent correlates of APP, explaining 37.9% of the variance, included a higher number of patients per psychiatrist (OR=1.04/10 patients, CI=1.03-1.06, p<0.001),lower proportion of males (OR=0.80, CI=0.74-0.86), younger age (OR=1.00, CI=0.99-1.00), several schizophrenia subtypes (paranoid: OR=1.24, CI=1.11-1.38,hebephrenic: OR=1.30, CI=1.03-1.63, other: OR=1.95 CI=1.17-3.24, unspecified: OR=1.21 CI=1.05-1.40), living alone (OR=1.12, CI=1.01-1.24), being institutionalized (OR=1.23, CI=1.06-1.42), receiving early retirement pension (OR=1.21, CI=1.10-1.34), higher Charlson Co-morbidity Index score (OR=1.13, CI=1.07-1.19), higher antipsychotic defined daily doses (OR=3.05, CI=-2.95-3.16), treatment with clozapine (OR=3.09, 95% CI=2.78-3.44), and treatment with antidepressants (OR=1.97 (CI=1.83-2.13), long-acting injectable antipsychotics (OR=1.48, CI=1.34-1.63), and anticholinergics (OR=1.74, CI=1.51-2.01). APP remains common in schizophrenia with substantial temporal and geographical variation
Kapur, Shitij; Agid, Ofer; Mizrahi, Romina; Li, Ming
How does a small molecule blocking a few receptors change a patients' passionately held paranoid belief that the FBI is out to get him? To address this central puzzle of antipsychotic action, we review a framework linking dopamine neurochemistry to psychosis, and then link this framework to the mechanism of action of antipsychotics. Normal dopamine transmission has a role in predicting novel rewards and in marking and responding to motivationally salient stimuli. Abnormal dopamine transmission alters these processes and results in an aberrant sense of novelty and inappropriate assignment of salience leading to the experience of psychosis. Antipsychotics improve psychosis by diminishing this abnormal transmission by blocking the dopamine D2/3 receptor (not D1 or D4), and although several brain regions may be involved, it is suggested that the ventral striatal regions (analog of the nucleus accumbens in animals) may have a particularly critical role. Contrary to popular belief, the antipsychotic effect is not delayed in its onset, but starts within the first few days. There is more improvement in the first 2 weeks, than in any subsequent 2-week period thereafter. However, a simple organic molecule cannot target the complex phenomenology of the individual psychotic experience. Antipsychotics diminish dopamine transmission and thereby dampen the salience of the pre-occupying symptoms. Therefore, in the initial stage of an antipsychotic response, the patients experience a detachment from symptoms, a relegation of the delusions and hallucinations to the back of their minds, rather than a complete erasure of the symptoms. Only with time, and only in some, via the mediation of new learning and plasticity, is there a complete resolution of symptoms. The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed.
Holden, Joseph; Palmer, Sheila M.; Johnston, Kerrylyn; Wearing, Catherine; Irvine, Brian; Brown, Lee E.
Fire is known to impact soil properties and hydrological flow paths. However, the impact of prescribed vegetation burning on blanket peatland hydrology is poorly understood. We studied 10 blanket peat headwater catchments. Five were subject to prescribed burning, while five were unburnt controls. Within the burnt catchments, we studied plots where the last burn occurred ˜2 (B2), 4 (B4), 7 (B7), or greater than 10 years (B10+) prior to the start of measurements. These were compared with plots at similar topographic wetness index locations in the control catchments. Plots subject to prescribed vegetation burning had significantly deeper water tables (difference in means = 5.3 cm) and greater water table variability than unburnt plots. Water table depths were significantly different between burn age classes (B2 > B4 > B7 > B10+) while B10+ water tables were not significantly different to the unburnt controls. Overland flow was less common on burnt peat than on unburnt peat, recorded in 9% and 17% of all runoff trap visits, respectively. Storm lag times and hydrograph recession limb periods were significantly greater (by ˜1 and 13 h on average, respectively) in the burnt catchments overall, but for the largest 20% of storms sampled, there was no significant difference in storm lag times between burnt and unburnt catchments. For the largest 20% of storms, the hydrograph intensity of burnt catchments was significantly greater than those of unburnt catchments (means of 4.2 × 10-5 and 3.4 × 10-5 s-1, respectively), thereby indicating a nonlinear streamflow response to prescribed burning. Together, these results from plots to whole river catchments indicate that prescribed vegetation burning has important effects on blanket peatland hydrology at a range of spatial scales.
Lapoint, Jeff; Perrone, Jeanmarie; Nelson, Lewis S
Errors in prescribing of dangerous medications, such as extended release or long acting (ER/LA) opioid forlmulations, remain an important cause of patient harm. Prescribing errors often relate to the failure to note warnings regarding contraindications and drug interactions. Many prescribers utilize electronic pharmacopoeia (EP) to improve medication ordering. The purpose of this study is to assess the ability of commonly used apps to provide accurate safety information about the boxed warning for ER/LA opioids. We evaluated a convenience sample of six popular EP apps available for the iPhone and an online reference for the presence of relevant safety warnings. We accessed the dosing information for each of six ER/LA medications and assessed for the presence of an easily identifiable indication that a boxed warning was present, even if the warning itself was not provided. The prominence of precautionary drug information presented to the user was assessed for each app. Provided information was classified based on the presence of the warning in the ordering pathway, located separately but within the prescribers view, or available in a separate screen of the drug information but non-highlighted. Each program provided a consistent level of warning information for each of the six ER/LA medications. Only 2/7 programs placed a warning in line with dosing information (level 1); 3/7 programs offered level 2 warning and 1/7 offered level 3 warning. One program made no mention of a boxed warning. Most EP apps isolate important safety warnings, and this represents a missed opportunity to improve prescribing practices.
... Navigation Bar Home Current Issue Past Issues The Web site your doctor prescribes Past Issues / Summer 2008 ... gov® is a free, comprehensive, up-to-date Web site with health information from the world's largest ...
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Albers, Lawrence James; Musenga, Alessandro; Raggi, Maria Augusta
Iloperidone is a new-generation atypical antipsychotic agent, acting as a serotonin/dopamine (5-HT(2A)/D(2)) antagonist, under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically, iloperidone is a benzisoxazole, like risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised. Several clinical trials have been carried out, to check efficacy, safety and side effects. In order to introduce iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important antipsychotic drugs available or under development will be reported. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results.
This article suggests that nurse prescribers require an awareness of key concepts in ethics, such as deontology and utilitarianism to reflect on current debates and contribute to them. The principles of biomedical ethics have also been influential in the development of professional codes of conduct. Attention is drawn to the importance of the Association of the British Pharmaceutical Industry's code of practice for the pharmaceutical industry in regulating marketing aimed at prescribers.
Le Couteur, David G; Kendig, Hal
Clinicians are becoming more reliant on their interpretation of clinical trial information to guide prescribing rather than their clinical skills. Thus to improve prescribing, it is increasingly important for clinicians to have an appreciation of epistemology (the science of knowledge and its interpretation) and the broader social context of knowledge. The insights of epistemologists can be useful in understanding the different ways in which clinical trials data are interpreted.
Fernández-Ortega, Paz; Cabrera-Jaime, Sandra; Estrada-Masllorens, Joan María
Objective: This study identifies the capability, knowledge, and satisfaction of oncology nurses in Spain after approval of the nurse prescribing law in 2006. Methods: A descriptive cross-sectional study was conducted among 140 nurses in three cancer centers in Catalonia, Spain, by using convenience sampling method. The principal variables of this study were nurse satisfaction, knowledge about what products nurses are allowed to prescribe, the nurses’ perception of their own prescribing ability, and their opinion on education and training needs with regard to the new approved law. The secondary variables included years of professional experience, place of work, and sociodemographic variables. Data were collected during a 3 months period by using a piloted 29-item self-assessment questionnaire. Results: Analyses of univariate and bivariate data showed that 82.2% of the nurses were aware of the approved law, but 94.2% indicated that they lack information about it. The mean satisfaction with the approval of the law was 6.64 ± 1.76 (numerical scale 0-10). In addition, 68.1% and 55.1% of the nurses were prepared to prescribe medical devices and drugs, respectively. To date, 61.1% of the nurses prescribe medical devices and 66% prescribe pharmacological products daily. Conclusions: Nurses expressed general satisfaction with the approval of the Law 29/2006. Nurses currently provide prescriptions, but widespread knowledge of the allowed prescriptions is lacking. PMID:27981146
Brzozowska, Natalia I; de Tonnerre, Erik J; Li, Kong M; Wang, Xiao Suo; Boucher, Aurelie A; Callaghan, Paul D; Kuligowski, Michael; Wong, Alex; Arnold, Jonathon C
Cannabis use increases rates of psychotic relapse and treatment failure in schizophrenia patients. Clinical studies suggest that cannabis use reduces the efficacy of antipsychotic drugs, but there has been no direct demonstration of this in a controlled study. The present study demonstrates that exposure to the principal phytocannabinoid, Δ(9)-tetrahydrocannabinol (THC), reverses the neurobehavioral effects of the antipsychotic drug risperidone in mice. THC exposure did not influence D2 and 5-HT2A receptor binding, the major targets of antipsychotic action, but it lowered the brain concentrations of risperidone and its active metabolite, 9-hydroxy risperidone. As risperidone and its active metabolite are excellent substrates of the ABC transporter P-glycoprotein (P-gp), we hypothesized that THC might increase P-gp expression at the blood-brain barrier (BBB) and thus enhance efflux of risperidone and its metabolite from brain tissue. We confirmed that the brain disposition of risperidone and 9-hydroxy risperidone is strongly influenced by P-gp, as P-gp knockout mice displayed greater brain concentrations of these drugs than wild-type mice. Furthermore, we demonstrated that THC exposure increased P-gp expression in various brain regions important to risperidone's antipsychotic action. We then showed that THC exposure did not influence the neurobehavioral effects of clozapine. Clozapine shares a very similar antipsychotic mode of action to risperidone, but unlike risperidone is not a P-gp substrate. Our results imply that clozapine or non-P-gp substrate antipsychotic drugs may be better first-line treatments for schizophrenia patients with a history of cannabis use.Neuropsychopharmacology advance online publication, 29 March 2017; doi:10.1038/npp.2017.50.
Reynolds, Matthew; Jheeta, Seetal; Benn, Jonathan; Sanghera, Inderjit; Jacklin, Ann; Ingle, Digby; Franklin, Bryony Dean
Background Prescribing errors occur in up to 15% of UK inpatient medication orders. However, junior doctors report insufficient feedback on errors. A barrier preventing feedback is that individual prescribers often cannot be clearly identified on prescribing documentation. Aim To reduce prescribing errors in a UK hospital by improving feedback on prescribing errors. Interventions We developed three linked interventions using plan–do–study–act cycles: (1) name stamps for junior doctors who were encouraged to stamp or write their name clearly when prescribing; (2) principles of effective feedback to support pharmacists to provide feedback to doctors on individual prescribing errors and (3) fortnightly prescribing advice emails that addressed a common and/or serious error. Implementation and evaluation Interventions were introduced at one hospital site in August 2013 with a second acting as control. Process measures included the percentage of inpatient medication orders for which junior doctors stated their name. Outcome measures were junior doctors' and pharmacists' perceptions of current feedback provision (evaluated using quantitative pre-questionnaires and post-questionnaires and qualitative focus groups) and the prevalence of erroneous medication orders written by junior doctors between August and December 2013. Results The percentage of medication orders for which junior doctors stated their name increased from about 10% to 50%. Questionnaire responses revealed a significant improvement in pharmacists' perceptions but no significant change for doctors. Focus group findings suggested increased doctor engagement with safe prescribing. Interrupted time series analysis showed no difference in weekly prescribing error rates between baseline and intervention periods, compared with the control site. Conclusion Findings suggest improved experiences around feedback. However, attempts to produce a measurable reduction in prescribing errors are likely to need a
Takeuchi, Hiroyoshi; Thiyanavadivel, Sadhana; Agid, Ofer; Remington, Gary
To address whether wait discontinuation (i.e., introducing the new antipsychotic while maintaining the first for a period before initiating its discontinuation) is superior to non-wait discontinuation (i.e., initiating the first antipsychotic's discontinuation when introducing the new antipsychotic) in antipsychotic switching, we conducted a meta-analysis of randomized controlled trials comparing gradual vs. wait-and-gradual antipsychotic discontinuation in patients with schizophrenia. The meta-analysis of 5 studies (n=410) demonstrated no significant differences in any clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, between the two groups. These findings indicate either strategy can be used in clinical practice.
Mattson, Margaret E; Albright, Victoria A; Yoon, Joanna; Council, Carol L
Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional). Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN) for prevalence of emergency department (ED) visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA. PMID:26056465
Qin, Rongyin; Chen, Yingzhu; Li, Ming
Among several commonly used atypical antipsychotic drugs, olanzapine and risperidone cause a sensitization effect in the conditioned avoidance response (CAR) and phencyclidine (PCP)-induced hyperlocomotion paradigms – two well established animal tests of antipsychotic drugs, whereas clozapine causes a tolerance effect. Asenapine is a novel antipsychotic drug recently approved for the treatment of schizophrenia and manic disorders. It shares several receptor binding sites and behavioral features with other atypical antipsychotic drugs. However, it is not clear what type of repeated effect (sensitization or tolerance) asenapine would induce, and whether such an effect is transferrable to other atypicals. In this study, male adult Sprague-Dawley rats were first repeatedly tested with asenapine (0.05, 0.10 or 0.20 mg/kg, sc) for avoidance response or PCP (3.20 mg/kg, sc)-induced hyperlocomotion daily for 5 consecutive days. After 2–3 days of retraining/drug-free recovery, they were then challenged with asenapine (0.10 mg/kg, sc), followed by olanzapine (0.50 mg/kg, sc) and clozapine (2.50 mg/kg, sc). During the 5-day drug test period (the induction phase), repeated asenapine treatment progressively increased its inhibition of avoidance response and PCP-induced hyperlocomotion in a dose-dependent fashion. On the asenapine and olanzapine challenge tests (the expression phase), rats previously treated with asenapine still showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle. An increased reactivity to clozapine challenge in prior asenapine-treated rats was also found in the PCP-induced hyperlocomotion test. These findings suggest that asenapine is capable of inducing a sensitization effect and a cross-sensitization to olanzapine and clozapine (to a lesser extent). Because the behavioral profile of asenapine in both tests is similar to that of olanzapine, but different from that of clozapine, we
Objective: Both first- (FGAs) and second-generation antipsychotics (SGAs) are routinely used in treating severe and persistent psychiatric disorders. However, until now no articles have analyzed systematically the safety of both classes of psychotropics during pregnancy. Data sources and search strategy: Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs. Search terms were pregnancy, psychotropic drugs, (a)typical-first-second-generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 2008. Data selection: All articles reporting primary data on the outcome of pregnancies exposed to antipsychotics were acquired, without methodological limitations. Conclusions: Reviewed information was too limited to draw definite conclusions on structural teratogenicity of FGAs and SGAs. Both classes of drugs seem to be associated with an increased risk of neonatal complications. However, most SGAs appear to increase risk of gestational metabolic complications and babies large for gestational age and with mean birth weight significantly heavier as compared with those exposed to FGAs. These risks have been reported rarely with FGAs. Hence, the choice of the less harmful option in pregnancy should be limited to FGAs in drug-naive patients. When pregnancy occurs during antipsychotic treatment, the choice to continue the previous therapy should be preferred. PMID:18787227
Just, Marek J
Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido), physiological arousal (lubrication/erection), orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic). Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. PMID:26185449
Simon, Elliott W.; And Others
The use of risperidone for 10 individuals with mental retardation and mental health disturbances was evaluated using a case study approach to delineate the course of substitution of more traditional antipsychotic medications with risperidone. All participants showed improvement or resolution in side effects attributed to previous medication with…
Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia
Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…
Schill, Johan; Olsson, Hans
Background: The objective of this study was to investigate the concordance in attitudes of psychiatrists towards the doses of antipsychotics given to stable outpatients with schizophrenia and to examine the psychiatrists’ estimates of equally potent doses of haloperidol and olanzapine. Methods: We asked all 22 doctors serving at the psychiatry department of Jönköping County Hospital if they considered the combined dose of antipsychotics for 20 individual patients to be ‘low’, ‘medium’ or ‘high’. We also asked each doctor to state the dose of haloperidol that they considered to be clinically equivalent to 20 mg/day of olanzapine. Results: The inter-rater reliability (Krippendorff’s alpha (α)) was 0.50, and the mean estimated dose haloperidol considered clinically equivalent to 20 mg/day of olanzapine was 4.45 mg/day. Conclusions: The inter-rater reliability (Krippendorff’s α) was low, suggesting lack of agreement. The dose of antipsychotics given to a patient might thus be more influenced by which doctor they meet than the severity of the disease. The respondents in this study considered a mean dose of 4.45 mg/day of haloperidol to be clinically equivalent to 20 mg/day of olanzapine. This is a considerably lower dose than was determined by an international consensus study of antipsychotic dosing, and more in line with the available PET studies measuring central dopamine receptor blockage of optimal clinical doses. PMID:28008348
Mierzejewski, Pawel; Kolaczkowski, Marcin; Marcinkowska, Monika; Wesolowska, Anna; Samochowiec, Jerzy; Pawlowski, Maciej; Bienkowski, Przemyslaw
Aside from their use in the treatment of anxiety disorders and insomnia, benzodiazepines and other GABAA receptor positive modulators are widely used as add-on treatments in schizophrenic and non-schizophrenic psychoses. However, there is relatively little direct clinical or pre-clinical evidence for antipsychotic effects of GABAergic medications. Previous studies have indicated that zolpidem, a GABAergic drug acting preferentially at α1-containing GABAA receptors, may produce catalepsy through interactions with dopaminergic neurotransmission. The aim of the present study was to investigate effects of zolpidem in experimental models of antipsychotic activity and extrapyramidal side effects in Wistar rats. Effects of zolpidem were compared with that of a classic benzodiazepine drug, diazepam and a second-generation antipsychotic medication, risperidone. High doses of risperidone (10.0mg/kg, i.p.) and zolpidem (10.0mg/kg, i.p.), but not diazepam, induced relatively short-lasting cataleptic responses in the bar test. Zolpidem and risperidone, but not diazepam, produced some antipsychotic-like effects at doses, which produced no catalepsy and did not inhibit spontaneous locomotor activity and apomorphine-induced stereotypies. The present results tend to indicate that zolpidem exerts some neuroleptic-like effects at doses, which do not produce motor side effects. Our findings may provide further rationale for the development of new subtype-selective GABAA receptor modulators for the treatment of psychotic symptoms.
Longman, Christine; Temple-Smith, Meredith; Gilchrist, Gail; Lintzeris, Nicholas
Opioid substitution therapy (OST) is a well-recognised, evidence-based treatment for opioid dependence. Since the early 1990s, Australia has used a community-based general practitioner (GP) model ofprescribing, particularly within the state of Victoria, where over 85% of OST prescribing is undertaken by GPs in community settings. Yet the majority of GPs invited to complete the required OST training decline the offer, while of those who complete training, the majority prescribe to few or no patients. This study aimed to determine the reasons for this. Twenty-two in-depth interviews were conducted with Victorian GPs exploring the reasons why the majority declined training, and for trained GPs, why they prescribed to few or no patients in the first 12 months after training. General practitioners who declined to train were predominantly influenced by negative experiences with drug-seeking patients, although other secondary reasons also affected their decision. Some GPs who completed the training were prevented from prescribing by several structural and operational barriers, many of which could be addressed. Fear of deskilling with time became a further impediment. General practitioners who became regular prescribers were highly committed with lengthy general practice experience. Concerns exist about the recruitment process for OST prescriber training, where nearly all GPs decline the offer of training, and the barriers that prevent GPs prescribing after training. Action is needed to address barriers to GP OST training and prescribing, and further research is necessary to ascertain measures required to facilitate long-term prescribing.
Johnson, Katrina C.; LaPrairie, Jamie L.; Brennan, Patricia A.; Stowe, Zachary N.; Newport, D. Jeffrey
Context Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce. Objective To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants. Design, Setting, and Participants A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n = 202), or no psychotropic agents (n = 85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face. Main Outcome Measures The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials. Results Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F2,281=4.51; P =.01; partial η2=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P’s<.05) and maternal depression during pregnancy was associated with less efficient habituation (r245=0.16; P <.02). There were no significant differences regarding habituation between medication exposure groups. Conclusions Among 6-month-old infants, a history of intrauterine antipsychotic
Rissmann, Robert; Dubois, Eline A; Franson, Kari L; Cohen, Adam F
The variability of drug response in different patients can be caused by various factors including age, change in renal function, co-medication and genotype. Traditionally, these personal variables are considered by clinicians prior to issuing a prescription. This paper provides an overview of a process to individualize prescribing for a patient with an emphasis on how to train (learning) clinicians in skillful rational prescribing. For this purpose the 6STEP methodology, a concept-based learning strategy to achieve a structured therapeutic plan, has been introduced. In contrast to older educational approaches which focused primarily on the drugs or the process of prescribing, the 6STEP is a patient-centred method resulting in individualized therapy. The six interlinked steps provide the (training) prescriber with a structured framework that facilitates a rationalized therapeutic decision by focusing on the individual patient parameters that influence drug response. Educational tools for rational prescribing involve understanding of basic and clinical pharmacological principles, practicing to write 6STEP therapeutic plans, learning from feedback sessions on these plans and actively obtaining up to date information on drugs and therapeutic standards from online resources. PMID:22420749
Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko
Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.
Brandl, E J; Tiwari, A K; Zai, C C; Nurmi, E L; Chowdhury, N I; Arenovich, T; Sanches, M; Goncalves, V F; Shen, J J; Lieberman, J A; Meltzer, H Y; Kennedy, J L; Müller, D J
Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59.
Easton, Stephanie; Pinchbeck, Gina L; Tzelos, Thomas; Bartley, David J; Hotchkiss, Emily; Hodgkinson, Jane E; Matthews, Jacqueline B
Helminths are common pathogens of equids and anthelmintic resistance is a major issue in cyathostomin species and Parascaris equorum. At the heart of mitigating the impact of increasing anthelmintic resistance levels, is the responsible dissemination and use of these medicines following best practice principles. There is a paucity of information on interactions between horse owners and anthelmintic prescribers and how this shapes control. Here, a study was undertaken to determine opinions and experiences of horse owners as they relate to anthelmintics purchase and implementation of best practice control. An online survey was distributed via email and social media to explore owners' experiences of purchasing anthelmintics from United Kingdom prescribers, these being veterinarians, suitably qualified persons (SQPs) and pharmacists. Owner responses (n=494) were analysed statistically to compare answers of respondents grouped according to: (i) from whom they bought anthelmintics (Veterinarians n=60; SQPs n=256; Pharmacists n=42; More than one channel n=136), and (ii) by which route (Face-to-face n=234; Telephone n=31; Online n=226) they purchased. Owners who purchased from veterinarians predominantly did so face-to-face (81.3%), whilst those that bought from SQPs purchased via face-to-face (48.8%) and online (46.0%) interactions. Those who purchased from pharmacists predominantly bought anthelmintics online (76.2%). Participants who bought from veterinarians were more likely to view certain factors (i.e. time to talk to the supplier, supplier knowledge) as more important than those who purchased from other prescribers. Those who purchased from veterinarians were more likely to be recommended faecal egg count (FEC) test analysis; however, there was high uptake of FEC testing across all groups. There was a low uptake of anthelmintic efficacy testing; regardless of the prescriber type from whom anthelmintics were purchased. Those who purchased from veterinarians were more
Michl, Johanna; Scharinger, Christian; Zauner, Miriam; Kasper, Siegfried; Freissmuth, Michael; Sitte, Harald H.; Ecker, Gerhard F.; Pezawas, Lukas
The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.000 patients) by the use of robust multivariate statistics. Orthogonal projection to latent structures (O-PLS) regression models with reasonable predictability were found for several frequent ADRs such as nausea, diarrhea, hypotension, dizziness, headache, insomnia, sedation, sleepiness, increased sweating, and weight gain. Results of the present study support many well-known pharmacological principles such as the association of hypotension and dizziness with α1-receptor or sedation with H1-receptor antagonism. Moreover, the analyses revealed novel or hardly investigated mechanisms for common ADRs including the potential involvement of 5-HT6-antagonism in weight gain, muscarinic receptor antagonism in dizziness, or 5-HT7-antagonism in sedation. To summarize, the presented study underlines the feasibility and value of a multivariate data mining approach in psychopharmacological development of antidepressants and antipsychotics. PMID:25044049
Kiefer, C. M.; Clements, C. B.; Potter, B. E.; Strenfel, S. J.
In situ radiosonde measurements were obtained during multiple prescribed fires at the Joseph W. Jones Ecological Research Center at Ichauway, Georgia in March and July of 2008. Data were obtained from prescribed fires conducted in longleaf pine ecosystems. After significant smoke generation was observed, radiosondes were launched downwind of the fire front and rose directly into the smoke plumes. Radiosondes were also launched before each burn to obtain ambient background conditions. This provided a unique dataset of smoke plume moisture to determine how moisture enhancement from fire smoke alters the dynamics of the smoke plume. Preliminary analysis of results show moisture enhancement occurred in all smoke plumes with relative humidity values increasing by 10 to 30 percent and water vapor mixing ratios increasing by 1 to 4 g kg-1. Understanding the moisture enhancement in prescribed fire smoke plumes will help determine the convective dynamics that occur in major wildland fires and convection columns.
Maxwell, Simon; Mucklow, John
Preparing medical students to prescribe is a major challenge of undergraduate education. They must develop an understanding of clinical pharmacology and acquire knowledge about drugs and therapeutics, as well as the skills to prescribe for individual patients in the face of multiple variables. The task of delivering the learning required to achieve these attributes relies upon limited numbers of teachers, who have increasingly busy clinical commitments. There is evidence that training is currently insufficient to meet the demands of the workplace. e-Learning provides an opportunity to improve the learning experience. The advantages for teachers are improved distribution of learning content, ease of update, standardization and tracking of learner activities. The advantages for learners are ease of access, greater interactivity and individual choice concerning the pace and mix of learning. Important disadvantages are the considerable resource required to develop e-Learning projects and difficulties in simulating some aspects of the real world prescribing experience. Pre-requisites for developing an e-Learning programme to support prescribing include academic expertise, institutional support, learning technology services and an effective virtual learning environment. e-Learning content might range from complex interactive learning sessions through to static web pages with links. It is now possible to simulate and provide feedback on prescribing decisions and this will improve with advances in virtual reality. Other content might include a student formulary, self-assessment exercises (e.g. calculations), a glossary and an on-line library. There is some evidence for the effectiveness of e-Learning but better research is required into its potential impact on prescribing. PMID:22509885
Ota, Takafumi; Miura, Itaru; Kanno-Nozaki, Keiko; Hoshino, Hiroshi; Horikoshi, Sho; Fujimori, Haruo; Kanno, Tomoyuki; Mashiko, Hirobumi; Yabe, Hirooki
Extrapyramidal symptoms (EPS) are common adverse effects of antipsychotic treatment. This study examined the effects of the traditional Japanese herbal medicine (kampo) shakuyaku-kanzo-to on EPS during antipsychotic treatment. Twenty-two Japanese patients with psychiatric disorders who had developed EPS during antipsychotic treatment were randomly allocated to receive either shakuyaku-kanzo-to (7.5 g/d) or biperiden (3 mg/d) for 2 weeks. Extrapyramidal symptoms were evaluated using the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) and the Barnes Akathisia Rating Scale. Plasma levels of the monoamine metabolite homovanillic acid and serum prolactin levels were measured to investigate the mechanisms of action of shakuyaku-kanzo-to. Twenty of the 22 patients completed the study (10 patients in the shakuyaku-kanzo-to group and 10 patients in the biperiden group). There was a time effect on the Drug-Induced Extrapyramidal Symptom Scale total score (P < 0.01), suggesting that both shakuyaku-kanzo-to and biperiden decreased EPS. Notably, there was a time × drug interaction in dystonia, suggesting that shakuyaku-kanzo-to had a greater effect on dystonia compared with biperiden. No significant changes were observed in plasma homovanillic acid or serum prolactin levels after 2 weeks of treatment in either group. The effects of shakuyaku-kanzo-to on abnormal muscle tonus and dopamine D2 receptors may have contributed to improve EPS. These results suggest that shakuyaku-kanzo-to may be useful in decreasing EPS, especially dystonia, in patients undergoing treatment with antipsychotic agents.
Whitworth, Maegan M; Haase, Krystal K; Fike, David S; Bharadwaj, Ravindra M; Young, Rodney B; MacLaughlin, Eric J
Background Scant literature exists evaluating utilization patterns for direct oral anticoagulants (DOACs). Objectives The primary objective was to assess DOAC prescribing in patients with venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF) in outpatient clinics. Secondary objectives were to compare utilization between family medicine (FM) and internal medicine (IM) clinics, characterize potentially inappropriate use, and identify factors associated with adverse events (AEs). Methods This was a retrospective cohort study of adults with NVAF or VTE who received a DOAC at FM or IM clinics between 10/19/2010 and 10/23/2014. Descriptive statistics were utilized for the primary aim. Fisher’s exact test was used to evaluate differences in prescribing using an adapted medication appropriateness index. Logistic regression evaluated factors associated with inappropriate use and AEs. Results One-hundred twenty patients were evaluated. At least 1 inappropriate criterion was met in 72 patients (60.0%). The most frequent inappropriate criteria were dosage (33.0%), duration of therapy (18.4%), and correct administration (18.0%). Apixaban was dosed inappropriately most frequently. There was no difference in dosing appropriateness between FM and IM clinics. The odds of inappropriate choice were lower with apixaban compared to other DOACs (odds ratio [OR]=0.088; 95% confidence interval [CI] 0.008–0.964; p=0.047). Twenty-seven patients (22.5%) experienced an AE while on a DOAC, and the odds of bleeding doubled with each inappropriate criterion met (OR=1.949; 95% CI 1.190–3.190; p=0.008). Conclusion Potentially inappropriate prescribing of DOACs is frequent with the most common errors being dosing, administration, and duration of therapy. These results underscore the importance of prescriber education regarding the appropriate use and management of DOACs. PMID:28331354
Coughlin, Catherine G.; Blackwell, Katherine A.; Bartley, Christine; Hay, Madeleine; Yonkers, Kimberly A.; Bloch, Michael H.
Objective Antipsychotic medications are used by increasing numbers of women of reproductive age. The safety of these medications during pregnancy has not been well-described. We undertook a systematic review and meta-analysis of the adverse obstetric and neonatal outcomes associated with exposure to antipsychotics during pregnancy. Data Sources PubMed, Reprotox, and ClinicalTrials.gov were searched to identify potential studies for inclusion. Methods of Study Selection Case-control or cohort studies estimating adverse birth outcomes associated with antipsychotic exposure during pregnancy were included. Pooled odds ratios (OR) were used for dichotomous outcomes and weighted mean differences (WMD) were used for infant birth weight and gestational age. Thirteen cohort studies, including 6,289 antipsychotic-exposed and 1,618,039 unexposed pregnancies were included. Tabulation, Integration, and Results Antipsychotic exposure was associated with an increased risk of major malformations (Absolute Risk Difference = 0.03, 95% confidence interval [CI] 0.00 – 0.05, p=0.04, Z = 2.06), heart defects (Absolute Risk Difference =0.01, 95% CI 0.00 – 0.01, p<0.001, Z = 3.44), preterm delivery (Absolute Risk Difference = 0.05, 95% CI 0.03 – 0.08, p<0.001, Z = 4.10), small-for-gestational-age births (Absolute Risk Difference = 0.05, 95% CI 0.02 – 0.09, p = 0.006, Z = 2.74), elective termination (Absolute Risk Difference = 0.09, 95% CI 0.05 – 0.13, p<0.001, Z = 4.69) and decreased birth weight (WMD=−57.89g, 95%CI −103.69g – −12.10g, p=0.01). There was no significant difference in the risk of major malformations (test for subgroup differences: χ2 = 0.07, df = 1, p = 0.79) between typical (OR = 1.55, 95% CI 1.21 – 1.99, p = 0.006) and atypical (OR = 1.39, 95% CI 0.66 – 2.93, p = 0.38) antipsychotic medications. Antipsychotic exposure was not associated with risk of large for gestational age births, stillbirth, and spontaneous abortion. Although antipsychotic
Lim, Jamie K.; Bratberg, Jeffrey P.; Davis, Corey S.; Green, Traci C.; Walley, Alexander Y.
In March of 2015, the United States Department of Health and Human Services identified 3 priority areas to reduce opioid use disorders and overdose, which are as follows: opioid-prescribing practices; expanded use and distribution of naloxone; and expansion of medication-assisted treatment. In this narrative review of overdose prevention and the role of prescribers and pharmacists in distributing naloxone, we address these priority areas and present a clinical scenario within the review involving a pharmacist, a patient with chronic pain and anxiety, and a primary care physician. We also discuss current laws related to naloxone prescribing and dispensing. This review was adapted from the Prescribe to Prevent online continuing medical education module created for prescribers and pharmacists (http://www.opioidprescribing.com/naloxone_module_1-landing). PMID:27261669
Grande, Iria; Vieta, Eduard
The use of combination therapy with mood stabilizers and antipsychotics in acute mania in bipolar disorder (BD) is widespread, although most treatment guidelines recommend monotherapy as the first option, and reserve combination therapy, which is associated with more frequent and more severe side effects, for when patients do not respond to the former treatment option. Reasons to prescribe combination therapy include the lack of efficacy of the current treatment (either real or due to undisclosed poor adherence), psychiatric comorbidities, severe previous course of illness, slow cross-tapering during treatment switching, and potential benefits from particular combinations. The decision to start with monotherapy or combination therapy may depend on the patient characteristics, and is still under debate. Clinical trials designed to ascertain whether combination therapy or monotherapy is more advantageous for patients in acute mania and beyond, according to illness severity, are urgently needed. Adding a third monotherapy arm to the conventional two-arm, adjunctive-design trials or initiating combination therapy from the beginning may help to shed some light on the issue.
Charani, E.; Castro-Sanchez, E.; Sevdalis, N.; Kyratsis, Y.; Drumright, L.; Shah, N.; Holmes, A.
Background. There is limited knowledge of the key determinants of antimicrobial prescribing behavior (APB) in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in antimicrobial stewardship programs. Methods. Qualitative semistructured interviews were conducted with doctors (n = 10), pharmacists (n = 10), and nurses and midwives (n = 19) in 4 hospitals in London. Interviews were conducted until thematic saturation was reached. Thematic analysis was applied to the data to identify the key determinants of antimicrobial prescribing behaviors. Results. The APB of healthcare professionals is governed by a set of cultural rules. Antimicrobial prescribing is performed in an environment where the behavior of clinical leaders or seniors influences practice of junior doctors. Senior doctors consider themselves exempt from following policy and practice within a culture of perceived autonomous decision making that relies more on personal knowledge and experience than formal policy. Prescribers identify with the clinical groups in which they work and adjust their APB according to the prevailing practice within these groups. A culture of “noninterference” in the antimicrobial prescribing practice of peers prevents intervention into prescribing of colleagues. These sets of cultural rules demonstrate the existence of a “prescribing etiquette,” which dominates the APB of healthcare professionals. Prescribing etiquette creates an environment in which professional hierarchy and clinical groups act as key determinants of APB. Conclusions. To influence the antimicrobial prescribing of individual healthcare professionals, interventions need to address prescribing etiquette and use clinical leadership within existing clinical groups to influence practice. PMID:23572483
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... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Forms prescribed. 479.21 Section 479.21 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...
... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Forms prescribed. 479.21 Section 479.21 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...
... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Forms prescribed. 479.21 Section 479.21 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND...
... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Forms prescribed. 478.21 Section 478.21 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION COMMERCE IN FIREARMS AND AMMUNITION...
Smith, W. E.
General mathematical expression found for energy storage shows that for linear, passive networks there is a minimum possible energy storage corresponding to a prescribed impedance. The electromagnetic energy storage is determined at different excitation frequencies through analysis of the networks terminal and reactance characteristics.
Gibson, Mark; Neil Jenkings, K; Wilson, Rob; Purves, Ian
This paper looks at aspects of doctor-patient communication and focuses on how prescribing decisions fit into the consultation within the context of the use (and non-use) of a technological clinical decision support system (CDSS) in the UK. Analysis of 6 simulated consultations filmed as part of the evaluation of a CDSS system indicated that the general practitioners (GPs) used their computers for a short time during consultations. The data showed that doctors' utterances, occurring at an early stage of the consultations, signalled the prescribing decision and eventual outcome of the consultation. The concept of 'verbal prescriptions' is used to describe these utterances of the GPs, and facilitates an understanding of how prescribing decisions are routinely achieved. Prescribing decisions can occur in the relatively early stages of the consultation, and both prior to and independently of the CDSS. Consequently, we suggest that the pattern of GP decision-making needs to be taken into account in CDSS design. However, this is not just an issue for CDSS design and implementation, as the verbal prescription phenomenon may impact upon patient involvement in decision-making, and even the appropriate use of evidence based medicine.
... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Forms prescribed. 20.21 Section 20.21 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF DENATURED ALCOHOL AND RUM Administrative...
... Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS CONTACT LENS RULE § 315.5 Prescriber verification. (a) Prescription requirement. A seller may sell contact lenses only in accordance with a contact lens prescription for the patient that is: (1) Presented to the seller by...
... Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS CONTACT LENS RULE § 315.5 Prescriber verification. (a) Prescription requirement. A seller may sell contact lenses only in accordance with a contact lens prescription for the patient that is: (1) Presented to the seller by...
... Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS CONTACT LENS RULE § 315.5 Prescriber verification. (a) Prescription requirement. A seller may sell contact lenses only in accordance with a contact lens prescription for the patient that is: (1) Presented to the seller by...
Debout, Christophe; Lescot, Thomas; Loyer, Frédérique; Ambrosino, Florence
While, in France, various health professionals are authorised to prescribe, they approach this activity in a different way, depending on the professional category to which they belong. The areas and products concerned are specific to each profession, and inevitably evolve. This article presents the different perspectives of a doctor, a midwife and a nurse.
..., TESTING, AND STANDARDS Cotton Fiber and Processing Tests Fiber and Processing Tests § 28.956 Prescribed fees. Fees for fiber and processing tests shall be assessed as listed below: Item number and kind of....0Furnishing international calibration cotton standards with standard values for micronaire reading and...
Hultgren, Philip B.; Burke, Edmund J., Jr.
This paper compares the methods for prescribing exercise according to various contemporary authorities. The programs are compared as to their goals, the testing modalities and physiological parameters used for prescription of the initial training session, and the methods and the progression of training. Regarding goals, there is a general…
... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Forms prescribed. 18.16 Section 18.16 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Administrative...
... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Forms prescribed. 18.16 Section 18.16 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Administrative...
Livingston Univ., AL. Coll. of Education.
This document contains 59 individually prescribed instructional modules for use in teacher aide education programs. Each module has six sections: 1) Behavioral objectives, 2) purpose, 3) performance criteria, 4) experiences, 5) resources, and 6) taxonomy. The subjects covered include the use of instructional equipment such as language master,…
Fleischhacker, W Wolfgang; Peuskens, Joseph; Cavallaro, Roberto; Lean, Michael EJ; Morozova, Margarita; Reynolds, Gavin; Azorin, Jean-Michel; Thomas, Pierre; Möller, Hans-Jürgen
Objectives: Antipsychotic drug side effects are common and can cause stigmatisation, decreased quality of life, poor adherence, and secondary morbidity and mortality. Systematic assessment of anticipated side effects is recommended as part of good clinical care, but is uncommon in practice and patients may not spontaneously report side effects. We aimed to develop a simple patient-completed checklist to screen systematically for potential antipsychotic side effects. Methods: The SMARTS checklist was developed over a series of group meetings by an international faculty of 12 experts (including psychiatrists, a general physician and a psychopharmacologist) based on their clinical experience and knowledge of the literature. The emphasis is on tolerability (i.e. assessment of side effects that ‘trouble’ the patient) as subjective impact of side effects is most relevant to medication adherence. The development took account of feedback from practising psychiatrists in Europe, the Middle East and Africa, a process that contributed to face validity. Results: The SMARTS checklist assesses whether patients are currently ‘troubled’ by 11 well-established potential antipsychotic side effects. Patients provide their responses to these questions by circling relevant side effects. An additional open question enquires about any other possible side effects. The checklist has been translated into Italian and Turkish. Conclusions: The SMARTS checklist aims to strike a balance between brevity and capturing the most common and important antipsychotic side effects. It is appropriate for completion by patients prior to a clinical consultation, for example, in the waiting room. It can then form the focus for a more detailed clinical discussion about side effects. It can be used alone or form part of a more comprehensive assessment of antipsychotic side effects including blood tests and a physical examination when appropriate. The checklist assesses current problems and can be used
McLellan, Lucy; Yardley, Sarah; Norris, Ben; de Bruin, Anique; Tully, Mary P; Dornan, Tim
Prescribing tasks, which involve pharmacological knowledge, clinical decision-making and practical skill, take place within unpredictable social environments and involve interactions within and between endlessly changing health care teams. Despite this, curriculum designers commonly assume them to be simple to learn and perform. This research used mixed methods to explore how undergraduate medical students learn to prescribe in the 'real world'. It was informed by cognitive psychology, sociocultural theory, and systems thinking. We found that learning to prescribe occurs as a dynamic series of socially negotiated interactions within and between individuals, communities and environments. As well as a thematic analysis, we developed a framework of three conceptual spaces in which learning opportunities for prescribing occur. This illustrates a complex systems view of prescribing education and defines three major system components: the "social space", where the environmental conditions influence or bring about a learning experience; the "process space", describing what happens during the learning experience; and the intra-personal "cognitive space", where the learner may develop aspects of prescribing expertise. This conceptualisation broadens the scope of inquiry of prescribing education research by highlighting the complex interplay between individual and social dimensions of learning. This perspective is also likely to be relevant to students' learning of other clinical competencies.
Mann, Theresa; Lamberts, Robert Patrick; Lambert, Michael Ian
Exercise prescribed according to relative intensity is a routine feature in the exercise science literature and is intended to produce an approximately equivalent exercise stress in individuals with different absolute exercise capacities. The traditional approach has been to prescribe exercise intensity as a percentage of maximal oxygen uptake (VO2max) or maximum heart rate (HRmax) and these methods remain common in the literature. However, exercise intensity prescribed at a %VO2max or %HRmax does not necessarily place individuals at an equivalent intensity above resting levels. Furthermore, some individuals may be above and others below metabolic thresholds such as the aerobic threshold (AerT) or anaerobic threshold (AnT) at the same %VO2max or %HRmax. For these reasons, some authors have recommended that exercise intensity be prescribed relative to oxygen consumption reserve (VO2R), heart rate reserve (HRR), the AerT, or the AnT rather than relative to VO2max or HRmax. The aim of this review was to compare the physiological and practical implications of using each of these methods of relative exercise intensity prescription for research trials or training sessions. It is well established that an exercise bout at a fixed %VO2max or %HRmax may produce interindividual variation in blood lactate accumulation and a similar effect has been shown when relating exercise intensity to VO2R or HRR. Although individual variation in other markers of metabolic stress have seldom been reported, it is assumed that these responses would be similarly heterogeneous at a %VO2max, %HRmax, %VO2R, or %HRR of moderate-to-high intensity. In contrast, exercise prescribed relative to the AerT or AnT would be expected to produce less individual variation in metabolic responses and less individual variation in time to exhaustion at a constant exercise intensity. Furthermore, it would be expected that training prescribed relative to the AerT or AnT would provide a more homogenous training
Kontopantelis, Evangelos; Akbarov, Artur; Rodgers, Sarah; Avery, Anthony J; Ashcroft, Darren M
Study question What is the prevalence of different types of potentially hazardous prescribing in general practice in the United Kingdom, and what is the variation between practices? Methods A cross sectional study included all adult patients potentially at risk of a prescribing or monitoring error defined by a combination of diagnoses and prescriptions in 526 general practices contributing to the Clinical Practice Research Datalink (CPRD) up to 1 April 2013. Primary outcomes were the prevalence of potentially hazardous prescriptions of anticoagulants, anti-platelets, NSAIDs, β blockers, glitazones, metformin, digoxin, antipsychotics, combined hormonal contraceptives, and oestrogens and monitoring by blood test less frequently than recommended for patients with repeated prescriptions of angiotensin converting enzyme inhibitors and loop diuretics, amiodarone, methotrexate, lithium, or warfarin. Study answer and limitations 49 927 of 949 552 patients at risk triggered at least one prescribing indicator (5.26%, 95% confidence interval 5.21% to 5.30%) and 21 501 of 182 721 (11.8%, 11.6% to 11.9%) triggered at least one monitoring indicator. The prevalence of different types of potentially hazardous prescribing ranged from almost zero to 10.2%, and for inadequate monitoring ranged from 10.4% to 41.9%. Older patients and those prescribed multiple repeat medications had significantly higher risks of triggering a prescribing indicator whereas younger patients with fewer repeat prescriptions had significantly higher risk of triggering a monitoring indicator. There was high variation between practices for some indicators. Though prescribing safety indicators describe prescribing patterns that can increase the risk of harm to the patient and should generally be avoided, there will always be exceptions where the indicator is clinically justified. Furthermore there is the possibility that some information is not captured by CPRD for some practices—for example, INR results in
Åstrand, Bengt; Petersson, Göran
Background The increased application of eServices in health care, in general, and ePrescribing (electronic prescribing) in particular, have brought quality and interoperability to the forefront. The application of standards has been put forward as one important factor in improving interoperability. However, less focus has been placed on other factors, such as stakeholders’ involvement and the measurement of interoperability. An information system (IS) can be regarded to comprise an instrument for technology-mediated work communication. In this study, interoperability refers to the interoperation in the ePrescribing process, involving people, systems, procedures and organizations. We have focused on the quality of the ePrescription message as one component of the interoperation in the ePrescribing process. Objective The objective was to analyze how combined efforts in improving interoperability with the introduction of the new national ePrescription format (NEF) have impacted interoperability in the ePrescribing process in Sweden, with the focus on the quality of the ePrescription message. Methods Consecutive sampling of electronic prescriptions in Sweden before and after the introduction of NEF was undertaken in April 2008 (pre-NEF) and April 2009 (post-NEF). Interoperability problems were identified and classified based on message format specifications and prescription rules. Results The introduction of NEF improved the interoperability of ePrescriptions substantially. In the pre-NEF sample, a total of 98.6% of the prescriptions had errors. In the post-NEF sample, only 0.9% of the prescriptions had errors. The mean number of errors was fewer for the erroneous prescriptions: 4.8 in pre-NEF compared to 1.0 in post-NEF. Conclusions We conclude that a systematic comprehensive work on interoperability, covering technical, semantical, professional, judicial and process aspects, involving the stakeholders, resulted in an improved interoperability of e
Tanjung, H. R.; Nasution, E. S.
The drug information literatures usually contains thousands of drugs, which much of them were rare or never prescribed by the physicians. It caused pharmacy students must learn thousands of drugs that will depleted resources and the study result was not effective. The aim of the study was to identify 200 items of drugs that mostly prescribed by the physicians in the pharmacies at Medan City. The study was a descriptive study that used a cross sectional survey methodology. The 200 items of drugs that mostly prescribed by the physician obtained from the pharmacies selected regarding to random sampling method. The study was conducted from August to September 2016. The 200 items of drugs that mostly prescribed by the physician resulted from 21.962 prescribed drugs item of 16.352 prescriptions of 100 pharmacies. The list revealed that the most prescribed drugs was amoxicilline (5.55 %), followed by dexamethasone (4.44%), mefenamic acid (3.73%), cetirizine (3.16%), and ciprofloxacine (2.97%). It shows that the antibiotic drug was the most prescribed drug by the physician in pharmacies at Medan City. Further studies are required to develop the study card from the list.
Porterfield, Amber; Engelbert, Kate; Coustasse, Alberto
Electronic prescribing (e-prescribing) is an important part of the nation's push to enhance the safety and quality of the prescribing process. E-prescribing allows providers in the ambulatory care setting to send prescriptions electronically to the pharmacy and can be a stand-alone system or part of an integrated electronic health record system. The methodology for this study followed the basic principles of a systematic review. A total of 47 sources were referenced. Results of this research study suggest that e-prescribing reduces prescribing errors, increases efficiency, and helps to save on healthcare costs. Medication errors have been reduced to as little as a seventh of their previous level, and cost savings due to improved patient outcomes and decreased patient visits are estimated to be between $140 billion and $240 billion over 10 years for practices that implement e-prescribing. However, there have been significant barriers to implementation including cost, lack of provider support, patient privacy, system errors, and legal issues.
Eum, Seenae; Lee, Adam M.; Bishop, Jeffrey R.
Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed. PMID:27757066
Calandre, Elena P; Rico-Villademoros, Fernando
Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2-4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the α(2)δ ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease. First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and
Argente Villaplana, Carlos R; Civera Andrés, Miguel; Real Collado, José T; Martínez-Hervás, Sergio; Ascaso Gimilio, Juan F; Carmena Rodríguez, Rafael
Drugs such as cocaine and atypical antipsychotic agents, such as olanzapine, are sometimes related to hyperglycemia. Whereas cocaine raises plasma glucose through catecholamine release, atypical antipsychotic agents mainly increase appetite and induce weight gain and the development of metabolic syndrome. Moreover, the latter group of drugs also act independently from weight gain or adiposity, due to inhibition of beta pancreatic cells and reduction of peripheral insulin action. We present the case of a 29-year-old non-diabetic woman with severe acute hyperglycemia in the context of a suicide attempt through intake of olanzapine and cocaine. After discontinuation of olanzapine and cocaine consumption, glycemia was immediately normalized without subsequent diagnosis of diabetes.
Eum, Seenae; Lee, Adam M; Bishop, Jeffrey R
Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed.
Poudel, Arjun; Peel, Nancye M; Mitchell, Charles A; Gray, Leonard C; Nissen, Lisa M; Hubbard, Ruth E
Objective In Australian residential aged care facilities (RACFs), the use of certain classes of high-risk medication such as antipsychotics, potent analgesics, and sedatives is high. Here, we examined the prescribed medications and subsequent changes recommended by geriatricians during comprehensive geriatric consultations provided to residents of RACFs via videoconference. Design This is a prospective observational study. Setting Four RACFs in Queensland, Australia, are included. Participants A total of 153 residents referred by general practitioners for comprehensive assessment by geriatricians delivered by video-consultation. Results Residents’ mean (standard deviation, SD) age was 83.0 (8.1) years and 64.1% were female. They had multiple comorbidities (mean 6), high levels of dependency, and were prescribed a mean (SD) of 9.6 (4.2) regular medications. Ninety-one percent of patients were taking five or more medications daily. Of total medications prescribed (n=1,469), geriatricians recommended withdrawal of 9.8% (n=145) and dose alteration of 3.5% (n=51). New medications were initiated in 47.7% (n=73) patients. Of the 10.3% (n=151) medications considered as high risk, 17.2% were stopped and dose altered in 2.6%. Conclusion There was a moderate prevalence of potentially inappropriate high-risk medications. However, geriatricians made relatively few changes, suggesting either that, on balance, prescription of these medications was appropriate or, because of other factors, there was a reluctance to adjust medications. A structured medication review using an algorithm for withdrawing medications of high disutility might help optimize medications in frail patients. Further research, including a broader survey, is required to understand these dynamics. PMID:26150708
Samara, Myrto T; Cao, Haoyin; Helfer, Bartosz; Davis, John M; Leucht, Stefan
It is one of the major psychiatric dogmas that the efficacy of all antipsychotic drugs is same. This statement originated from old, narrative reviews on first-generation antipsychotics, but this old literature has never been meta-analysed. We therefore conducted a meta-analysis of randomised controlled trials on the efficacy of chlorpromazine versus any other antipsychotic in the treatment of schizophrenia. If the benchmark drug chlorpromazine were significantly more or less effective than other antipsychotics, the notion of equal efficacy would have to be rejected. We searched the Cochrane Schizophrenia Group׳s specialized register, MEDLINE, EMBASE, PsychInfo and reference lists of relevant articles. The primary outcome was response to treatment. We also analyzed mean values of schizophrenia rating scales at endpoint and drop-out rates. 128, mostly small, RCTs with 10667 participants were included. Chlorpromazine was compared with 43 other antipsychotics and was more efficacious than four (butaperazine, mepazine, oxypertine and reserpine) and less efficacious than other four antipsychotics (clomacran, clozapine, olanzapine and zotepine) in the primary outcome. There were no statistically significant efficacy differences between chlorpromazine and the remaining 28 antipsychotics. The most important finding was that, due to low numbers of participants (median 50, range 8-692), most comparisons were underpowered. Thus we infer that the old antipsychotic drug literature was inconclusive and the claim for equal efficacy of antipsychotics was never evidence-based. Recent meta-analyses on second-generation antipsychotics were in a better position to address this question and small, but consistent differences between drugs were found.
Mailman, Richard B.; Murthy, Vishakantha
Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second). It has been widely recognized recently that this phenomenon impacts the understanding of mechanism of action of some drugs, and has relevance to drug discovery. One of the clinical areas where this mechanism has particular importance is in the treatment of schizophrenia. Antipsychotic drugs have been grouped according to both pattern of clinical action and mechanism of action. The original antipsychotic drugs such as chlorpromazine and haloperidol have been called typical or first generation. They cause both antipsychotic actions and many side effects (extrapyramidal and endocrine) that are ascribed to their high affinity dopamine D2 receptor antagonism. Drugs such as clozapine, olanzapine, risperidone and others were then developed that avoided the neurological side effects (atypical or second generation antipsychotics). These compounds are divided mechanistically into those that are high affinity D2 and 5-HT2A antagonists, and those that also bind with modest affinity to D2, 5-HT2A, and many other neuroreceptors. There is one approved third generation drug, aripiprazole, whose actions have been ascribed alternately to either D2 partial agonism or D2 functional selectivity. Although partial agonism has been the more widely accepted mechanism, the available data are inconsistent with this mechanism. Conversely, the D2 functional selectivity hypothesis can accommodate all current data for aripiprazole, and also impacts on discovery compounds that are not pure D2 antagonists. PMID:19909227
McClay, Joseph L.; Adkins, Daniel E.; Åberg, Karolina; Stroup, Scott; Perkins, Diana O.; Vladimirov, Vladimir I.; Lieberman, Jeffrey A.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.
Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenic patients to the most effective and safe medication. Here we use a genomewide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Subjects were genotyped using the Affymetrix 500K genotyping platform plus a custom 164K chip to improve genomewide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale (PANSS). Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our pre-specified threshold and involved a SNP in an intergenic region on chromosome 4p15. In addition, SNPs in ANKS1B and CNTNAP5 that mediated the effects of olanzapine and risperidone on Negative symptoms were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino acid substitution. In addition to highlighting our top results, we provide all p-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of GWAS to discover novel genes that mediate effects of antipsychotics, which eventually could help to tailor drug treatment to schizophrenic patients. PMID:19721433
Francis, Nick A.; Hood, Kerenza; Lyons, Ronan; Butler, Christopher C.
Objectives The volume of prescribed antibiotics is associated with antimicrobial resistance and, unlike most other antibiotic classes, flucloxacillin prescribing has increased. We aimed to describe UK primary care flucloxacillin prescribing and factors associated with subsequent antibiotic prescribing as a proxy for non-response. Patients and methods Clinical Practice Research Datalink patients with acute prescriptions for oral flucloxacillin between January 2004 and December 2013, prescription details, associated Read codes and patient demographics were identified. Monthly prescribing rates were plotted and logistic regression identified factors associated with having a subsequent antibiotic prescription within 28 days. Results 3 031 179 acute prescriptions for 1 667 431 patients were included. Average monthly prescription rates increased from 4.74 prescriptions per 1000 patient-months in 2004 to 5.74 (increase of 21.1%) in 2013. The highest prescribing rates and the largest increases in rates were seen in older adults (70+ years), but the overall increase in prescribing was not accounted for by an ageing population. Prescribing 500 mg tablets/capsules rather than 250 mg became more common. Children were frequently prescribed low doses and small volumes (5 day course) and prescribing declined for children, including for impetigo. Only 4.2% of new prescriptions involved co-prescription of another antibiotic. Age (<5 and ≥60 years), diagnosis of ‘cellulitis or abscess’ or no associated code, and 500 mg dose were associated with a subsequent antibiotic prescription, which occurred after 17.6% of first prescriptions. Conclusions There is a need to understand better the reasons for increased prescribing of flucloxacillin in primary care, optimal dosing (and the need to co-prescribe other antibiotics) and the reasons why one in five patients are prescribed a further antibiotic within 4 weeks. PMID:27090629
Higgins, H M; Golding, S E; Mouncey, J; Nanjiani, I; Cook, A J C
In the United Kingdom, blanket antibiotic dry cow therapy (BDCT) is commonly prescribed. An alternate strategy is selective dry cow therapy (SDCT) whereby a teat sealant is given instead of an antibiotic to cows with a low probability of infection. Switching from BDCT to SDCT can significantly reduce antibiotic use. The aims of this study were to explore how veterinarians (vets) rationalized their prescribing decisions for mammary treatments at drying off, and the barriers and motivators they perceived to implementing SDCT. Face-to-face interviews were conducted with 20 purposively recruited vets from 6 practices in England, United Kingdom. The data were analyzed qualitatively using an inductive thematic analysis. The majority of participants stated a personal preference for SDCT because it constitutes more responsible antibiotic use. On the majority of farms, the prescribing decision was taken by a senior veterinarian and BDCT was prescribed. Less experienced vets expressed a desire to be more involved in the decision-making process. The first theme, prioritizing responsible antimicrobial prescribing, encapsulated the difficulties vets expressed engaging with farmers, conflicts of interest, and vets' determination to take action. The second theme, the effect of a vet's experience on their ability to influence farmers, focused on the specific challenges faced by less experienced vets and the importance of vets being both trusted by farmers and being knowledgeable. The third theme, vets' perceptions about the risk and complexity of implementing SDCT, revealed markedly different levels of concern and fears about adverse outcomes with teat sealants versus antibiotics. The results also showed differences in perceptions about how difficult SDCT is to implement in practice. The last theme, vets' suggestions for facilitating the introduction of SDCT, was wide ranging and provided useful insight from a veterinary perspective into ways to facilitate SDCT. Initiatives that
Osborn, Dpj; Marston, L; Nazareth, I; King, M B; Petersen, I; Walters, K
Antipsychotics may confer long term benefits and risks, including cardiovascular disease (CVD) risk. Several studies using routine clinical data have reported associations between antipsychotics and CVD but potential confounding factors and unclear classification of drug exposure limits their interpretation.
Patteet, Lisbeth; Cappelle, Delphine; Maudens, Kristof E; Crunelle, Cleo L; Sabbe, Bernard; Neels, Hugo
Measuring antipsychotic concentrations in human matrices is important for both therapeutic drug monitoring and forensic toxicology. This review provides a critical overview of the analytical methods for detection and quantification of antipsychotics published in the last four years. Focus lies on advances in sample preparation, analytical techniques and alternative matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used most often for quantification of antipsychotics. This sensitive technique makes it possible to determine low concentrations not only in serum, plasma or whole blood, but also in alternative matrices like oral fluid, dried blood spots, hair, nails and other body tissues. Current literature on analytical techniques for alternative matrices is still limited and often requires a more thorough validation including a comparison between conventional and alternative results to determine their actual value. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) makes it possible to quantify a high amount of compounds within a shorter run time. This technique is widely used for multi-analyte methods. Only recently, high-resolution mass spectrometry has gained importance when a combination of screening of (un)known metabolites, and quantification is required.
Bargiota, S. I.; Bonotis, K. S.; Messinis, I. E.; Angelopoulos, N. V.
Introduction. Typical and atypical antipsychotic agent is currently used for treatment in the majority of patients with psychotic disorders. The aim of this review is to assess antipsychotic induced hyperprolactinaemia and the following menstrual dysfunction that affects fertility, quality of life, and therapeutic compliance of women. Method. For this purpose, Medline, PsychInfo, Cochrane library, and Scopus databases were accessed, with a focus on the publication dates between 1954 and 2012. Research of references was also performed and 78 studies were retrieved and used for the needs of this review. Results. A summary of several antipsychotics as well as frequency rates and data on hyperprolactinaemia and menstrual disorders for different agent is presented. Conclusion. Diverse prevalence rates of hyperprolactinaemia and menstrual abnormalities have been found about each medication among different studies. Menstruation plays an important role for women, thus, understanding, careful assessment, and management of hyperprolactinaemia could enhance their lives, especially when dealing with women that suffer from a psychotic disorder. PMID:24490071
Bo, Qi-Jing; Wang, Zhi-Min; Li, Xian-Bin; Ma, Xin; Wang, Chuan-Yue; de Leon, Jose
This systematic review examines adjunctive metformin therapy for the treatment of antipsychotic-induced hyperprolactinemia. A computerized search of databases in Chinese and the international databases in English provided three trials with a total of 325 patients including one randomized clinical trial (RCT) and two observational studies (single-group, before-after design). A meta-analysis could not be conducted. The quality of evidence ranged from "very low" to "moderate". Metformin patients had a significant decrease in serum prolactin level with a mean of 54.6μg/l in the three trials. In the RCT, menstruation restarted in 67% of those with menstrual disturbances versus 5% in placebo. In one observational study, 91% of patients no longer had signs or symptoms of galactorrhea. In the RCT, adverse drug reactions (ADRs) occurred at similar incidence rates among metformin and placebo patients, except that no significant increases in nausea, insomnia and agitation occurred which were not associated with discontinuations. Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia. Future higher quality RCTs need to verify the currently available limited evidence based on three trials which suggest that adjunctive metformin may be used effectively and safely for antipsychotic-induced hyperprolactinemia.
Salomon, C; Hamilton, B; Elsom, S
Despite high reported rates of antipsychotic non-adherence, little is known about consumer experiences during discontinuation. This study was designed to increase understanding of antipsychotic discontinuation from consumer perspectives. In 2011-2012, 98 Australian consumers involved with participating organizations completed an anonymous survey detailing past antipsychotic discontinuation attempts. Of the 88 participants who reported at least one discontinuation attempt, over half (n = 47, 54.7%) reported stopping without clinician knowledge or support. This group was 35% (confidence interval 15.4-54.6%) more likely to stop abruptly than those (n = 41, 45.3%) stopping with clinician support (P = 0.002). Only 10 participants (23.3%) recalled being given information about discontinuation symptoms other than relapse; however, 68 participants (78.2%) reported experiencing a range of discontinuation symptoms including physical, cognitive, emotional, psychotic or sleep-related disturbances. Findings cannot be readily generalized because of sampling constraints. However, the significant number of participants who reported discontinuation symptoms, in addition to psychosis, is consistent with previous research. This study provides new insight into consumer motivations for discontinuation and possible problems in clinical communication that may contribute to frequent non-collaborative discontinuation attempts. Mental health nurses, who play a pivotal role in medication communication events, may benefit from increased awareness of consumer perspectives on this topic.
Abdallah, Nihad; Conn, Rory; Latif Marini, Abdel
Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service.
Kukla, M J; Bloss, J L; Brougham, L R
A number of molecular similarities between the antipsychotic agents butaclamol and clozapine were noted. Based on the premise that this was a strong indicator of a common mechanism of action (i.e., binding at the antagonist state of the dopamine receptor), a research approach was described. Three simplified analogues (4,8, and 12a) of butaclamol which still retained the molecular functionalities of the parent structure were synthesized and tested in the haloperidol receptor assay. 1-(5-Methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene)-4-tert-butyl-4-piperidine (12a) displaced tritiated haloperidol with an IC50 value of 2.4 nM, as compared to a value of 0.5 nM for butaclamol However, when 12a was tested in vivo or in the spiroperidol receptor assay it was found to be considerably less potent.
Treatment of schizophrenic illness usually involves the long-term administration of antipsychotic drugs. Most antipsychotic agents antagonise the actions of endogenous dopamine (DA) at DA-2 receptors in the brain. The relative affinity for, and binding time to, DA-2 receptors was considered to be one of the key determinants of the antipsychotic potency of classical antipsychotic drugs. Some newer atypical antipsychotics, of which clozapine is the prototype, have a relatively poor affinity for DA-2 receptors; whereas other atypical antipsychotics are potent DA-2 antagonists. The propensity of antipsychotic agents to cause hyperprolactinaemia is related to their potency in antagonising DA-2 receptors on the anterior pituitary. In our studies, bone loss was consistently related to DA-2 antagonist potency of antipsychotic drugs, rather than their classification using conventional 'typical' versus 'atypical' systems. It is established that hyperprolactinaemia causes suppression of the reproductive endocrine axis and consequent bone mineral density (BMD) loss. Results from our group and others have demonstrated that a similar pathophysiological process is occurring in individuals with antipsychotic-induced hyperprolactinaemia. We found high rates of osteoporosis and osteopenia in those taking long-term antipsychotic drugs, and this was related to the dose and duration of treatment. Bone loss was associated with hypogonadism in male and female groups. Young Caucasian women appear to be particularly vulnerable to developing hyperprolactinaemia and the associated hypogonadism and bone loss. The occurrence of menstrual dysfunction should alert clinical suspicions of hyperprolactinaemia and bone de-mineralisation. Lastly, there are no published trials examining the effects of hormone replacement on BMD in those taking long-term antipsychotic drugs, but preliminary findings from our studies suggest that active management of bone loss in those with antipsychotic-associated bone
Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus
Introduction Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. Objective To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. Method A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider´s perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. Results 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Conclusion Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money
Boonlue, Tuanthon; Subongkot, Suphat; Dilokthornsakul, Piyameth; Kongsakon, Ronnachai; Pattanaprateep, Oraluck; Suanchang, Orabhorn; Chaiyakunapruk, Nathorn
Background Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. Results A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23–2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57–3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (−$64; 95% CI −$459 to $332). Conclusion Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization
Czarniak, Petra; Bint, Lewis; Favié, Laurent; Parsons, Richard; Hughes, Jeff; Sunderland, Bruce
Purpose To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. Methods A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. Results A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). Conclusion This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the
Little, Paul; Watson, Louise; Morgan, Stephen; Williamson, Ian
BACKGROUND: Systematic reviews of antibiotic treatment of common acute respiratory tract infections (RTIs) suggest modest symptomatic benefit, but provide limited evidence that prescribing prevents complications. AIM: To assess the relationship between penicillin prescribing (the most commonly used group of antibiotics for RTIs) and hospital admission with complications. DESIGN OF STUDY: Data linkage study. SETTING: Ninety-six health authorities of England for the year 1997-1998. METHOD: Hospital admissions related to RTIs were linked with prescribing analysis and cost (PACT) data. RESULTS: There was close correlation between items of penicillin use and total antibiotic use (r = 0.96). After controlling for SMR, age, sex, and Townsend score, a one-unit increase in penicillin use (items dispensed per capita) was associated with a reduction in annual incidence per 10,000 of admissions for quinsy (-3.55 admissions, 95% confidence interval [CI] = -6.85 to -0.26), and mastoiditis (square root of incidence of admissions = -1.05, 95% CI = -1.82 to -0.27). This does not represent lower referral thresholds among higher prescribers as higher prescribing was associated with more admissions for tonsillectomy and overall admissions. Increasing prescribing by 2000 items of penicillin for a practice of 10,000 patients could possibly prevent one admission for either mastoiditis or quinsy. CONCLUSION: Higher antibiotic prescribing is associated with significantly fewer admissions with major complications. However, the overall size of the effect is modest and it is difficult to advocate an overall increase in prescribing to prevent complications. Future research should concentrate on finding better methods of targeting antibiotics to individuals at risk of poor outcome. PMID:12030660
Kamarudin, Gritta; Penm, Jonathan; Chaar, Betty; Moles, Rebekah
Objective To review the literature on educational interventions to improve prescribing and identify educational methods that improve prescribing competency in both medical and non-medical prescribers. Design A systematic review was conducted. The databases Medline, International Pharmaceutical Abstracts (IPA), EMBASE and CINAHL were searched for articles in English published between January 1990 and July 2013. Setting Primary and secondary care. Participants Medical and non-medical prescribers. Intervention Education-based interventions to aid improvement in prescribing competency. Primary outcome Improvements in prescribing competency (knows how) or performance (shows how) as defined by Miller's competency model. This was primarily demonstrated through prescribing examinations, changes in prescribing habits or adherence to guidelines. Results A total of 47 studies met the inclusion criteria and were included in the systematic review. Studies were categorised by their method of assessment, with 20 studies assessing prescribing competence and 27 assessing prescribing performance. A wide variety of educational interventions were employed, with different outcome measures and methods of assessments. In particular, six studies demonstrated that specific prescribing training using the WHO Guide to Good Prescribing increased prescribing competency in a wide variety of settings. Continuing medical education in the form of academic detailing and personalised prescriber feedback also yielded positive results. Only four studies evaluated educational interventions targeted at non-medical prescribers, highlighting that further research is needed in this area. Conclusions A broad range of educational interventions have been conducted to improve prescribing competency. The WHO Guide to Good Prescribing has the largest body of evidence to support its use and is a promising model for the design of targeted prescribing courses. There is a need for further development and evaluation
Gill, Sudeep S; Rochon, Paula A; Herrmann, Nathan; Lee, Philip E; Sykora, Kathy; Gunraj, Nadia; Normand, Sharon-Lise T; Gurwitz, Jerry H; Marras, Connie; Wodchis, Walter P; Mamdani, Muhammad
Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an atypical antipsychotic and 14 865 dispensed a typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics. PMID:15668211
Mahoney, Diane Feeney; Ladd, Elissa
The purpose of this study was to gain understanding about nurse practitioners' (NPs') prescriptive decision making for geriatric patients with attention to pharmaceutical marketing influences. Prior research has focused on physician prescribers and identified suboptimal practices. Because the majority of medications are prescribed to older adults, NPs in geriatric practice were targeted as an information-rich group to interview about prescribing issues. Given the exploratory nature of this research, qualitative focus group methods were employed using content analysis. Fifteen NPs were recruited at an annual national geriatric NP conference. They worked in all regions of the United States, had an average of 9 years prescribing experience, and participated in 1 of the 2 focus groups. The key theme that emerged was that they were more than a prescriber. Findings revealed overwhelming consistency among the NP participants that their nursing background instilled a holistic approach that encompassed both nondrug and therapeutic drug options and skepticism about drug marketing, as well as offered a positive difference by tailoring to their patients' biophysical, psychological, and economic needs with an involvement in the interplay of geriatric care issues not typically addressed by physicians. The participants' reported approaches were in alignment with geriatric prescribing recommendations.
Neubert, Antje; Wimmer, Stefan
Paediatric prescribing is complex. A whole range of aspects needs to be considered to achieve an efficacious and safe drug therapy for children. Legal requirements for prescribing are clearly insufficient for this purpose. Children are immature individuals under constant growth and development. Consequently, based on age and cognitive abilities of the child individual drugs and dosing regimens have to be chosen. Frequent off-label use and a lack of age-appropriate formulation worsen the situation. Additionally, not all dosage forms are similarly adequate in different age groups. Taste significantly influences patient adherence. Dose calculations based on body weight are prone to errors, putting a point on the wrong place or mixing up measuring units easily result in ten-fold dosing errors. Computer-based tools to enhance prescribing are promising but, however, not yet widely implemented in paediatrics because of missing evidence-based data sources and the hugely complex process. Communication between clinicians and pharmacists as well as with the patient remains very important.
Sears, M R; Rea, H H; Fenwick, J; Gillies, A J; Holst, P E; O'Donnell, T V; Rothwell, R P
The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma. Images p480-a PMID:3103732
Angelini, A; Ciofani, G; Conti, P
Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains one of the major obstacles to effective cancer chemotherapy. Several chemosensitizers have been used in vivo and in vitro to reverse MDR but have exhibited several unwanted side effects. Antipsychotics are often administered to treat psychiatric disorders such as delirium, anxiety and sleep disorders in cancer patients during chemotherapy. The present in vitro study, examined the effects of two common antipsychotic compounds, haloperidol and risperidone, and a natural compound such as theobromine on reversing MDR Pgp-mediated, to evaluate their potential use as chemosensitizing agents. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp (100-fold), were treated with the antipsychotic alone (1, 10 and 20 μM) or in combination with different concentrations of doxo (2, 4 and 8 μM). The accumulation and cytotoxicity of doxo (MTT assay) and cellular GSH content (GSH assay) in comparison with verapamil, a well-known Pgp inhibitor, used as reference molecule were examined. It was found that the three compounds significantly enhanced the intracellular accumulation of doxo in resistant cancer cells, when compared with cells receiving doxo alone (p<0.05). Furthermore, compounds showed strong potency to increase doxo cytotoxicity toward resistant MES-SA/Dx5 cells, when compared with untreated control cells. The antipsychotic compounds also significantly increased GSH content at all concentrations (> 30%) in resistant cells, when compared to untreated control cells (p<0.05). These findings suggest that the antipsychotics or their derivatives might represent a novel class of reversal agents for overcoming MDR in cancer therapy, in particular theobromine showed to be an effective Pgp inhibitor with the lowest toxicity.
Reed-Kane, Dana; Kittell, Katrina; Adkins, Jacquelyn; Flocks, Sarah; Nguyen, Thu
Errors during the prescribing process can cause problems for patients. When the pharmacist intercepts a prescribing error, it can cause a delay, as the patient may not receive the medication until the problem is resolved. Electronic prescriptions are purported to reduce prescribing errors. However, studies have shown that electronic prescriptions can be prone to certain types of errors. Compounding pharmacies may present an additional obstacle for e-prescribing, as the prescribed medications are not commercially available and may not be listed in the e-prescribing software. The objectives of this study were to estimate the electronic prescription error rate in a compounding pharmacy, determine the most common error types, list the most common interventions pharmacists made, and estimate how long it took to resolve these errors. The study design was quality improvement with descriptive data. During the four weeks of data collection, the pharmacists were trained to complete a standardized data collection form when they identified an electronic prescription error. Percentages were calculated for new prescriptions, electronic prescriptions with errors, error types, and error resolution methods. In the four-week period of the study, there were 982 new prescriptions, 111 of which were electronic prescriptions. Of those 111 electronic prescriptions, 70 had errors. The electronic prescriptions error rate was 63%. The most common type of error was wrong entry field (70.3%). For this project, wrong entry field was defined to mean that the drug name was in the wrong field (81%) or that multiple entries were in the wrong field (7%). Pharmacists usually used their own judgment to resolve an error (67%). Many e-prescription errors were identified in this compounding pharmacy. When prescription errors happen, workflow and patient care are disrupted. Our goal is to discuss these findings with Surescripts and e-prescribing software companies to seek systems-based solutions.
Seeman, Mary V; Ross, Ruth
Although women with serious mental illness have high rates of lifetime sexual partners, they infrequently use contraception. Consequently, the prevalence of sexually transmitted infections is high in this population. In addition, while the overall rate of pregnancy in women with schizophrenia of child-bearing age is lower than in the general population, the percentage of pregnancies that are unwanted is higher than that in the general population. The objective of this paper is to help clinicians explore knowledge of appropriate methods of contraception for women who suffer from schizophrenia. The authors reviewed recent literature on the use of contraceptive methods by women with schizophrenia treated with antipsychotic and adjunctive medications. Contraceptive counseling to women and their partners is an important part of comprehensive care for women with serious and persistent mental illness. Women with schizophrenia who smoke, are overweight, or have diabetes, migraine, cardiovascular disease, or a family history of breast cancer should be offered non-hormonal contraception. Women with more than one sexual partner should be advised on barrier methods in addition to any other contraceptive measures they are using. Clinicians should be alert for potential interactions among oral hormonal contraceptives, smoking, and therapeutic drugs. Long-lasting contraceptive methods, such as intrauterine devices, progesterone depot injections, or tubal ligation are reasonable options for women having no wish to further expand their families.
Lako, Irene M; Taxis, Katja; van den Heuvel, Edwin R; Leenaars, Cathalijn H C; Burger, Huibert; Wiersma, Durk; Slooff, Cees J; Knegtering, Henderikus; Bruggeman, Richard
Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their antipsychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients' relatively low dose range, altered emotional experiences did not appear to relate to the level of D2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033-2.015]); possibly due to higher D2 receptor occupancies as estimated by dose equivalents.
Toledo, David; Kreuter, Urs P; Sorice, Michael G; Taylor, Charles A
Risk and liability concerns regarding fire affect people's attitudes toward fire and have led to human-induced alterations of fire regimes. This has, in turn, contributed to brush encroachment and degradation of many grasslands and savannas. Efforts to successfully restore such degraded ecosystems at the landscape scale in regions of the United States with high proportions of private lands require the reintroduction of fire. Prescribed Burn Associations (PBA) provide training, equipment, and labor to apply fire safely, facilitating the application of this rangeland management tool and thereby reducing the associated risk. PBAs help build networks and social capital among landowners who are interested in using fire. They can also change attitudes toward fire and enhance the social acceptability of using prescribed fire as a management practice. PBAs are an effective mechanism for promoting the widespread use of prescribed fire to restore and maintain the biophysical integrity of grasslands and savannas at the landscape scale. We report findings of a project aimed at determining the human dimensions of using prescribed fire to control woody plant encroachment in three different eco-regions of Texas. Specifically, we examine membership in PBAs as it relates to land manager decisions regarding the use of prescribed fire. Perceived risk has previously been identified as a key factor inhibiting the use of prescribed fire by landowners. Our results show that perceived constraints, due to lack of skill, knowledge, and access to equipment and membership in a PBAs are more important factors than risk perceptions in affecting landowner decisions about the use of fire. This emphasizes the potential for PBAs to reduce risk perceptions regarding the application of prescribed fire and, therefore, their importance for restoring brush-encroached grasslands and savannas.
Honoré, Mitonga Kabwebwe; Lubbe, Martie; Serfontein, Jan; Allen, Kirk
The therapeutic impact of inappropriate prescribing of antibiotics is debatable, particularly in situations where infections are treated empirically with multiply prescribed antibiotics. Prescribers may remain under the illusion that such prescriptions are appropriate on the basis of any observed positive treatment outcomes, even though an antibiotic prescribed in such combination therapy may actually be infective against infecting pathogens. This, inevitably, promotes inappropriate antibiotic prescribing. Prescribers may be motivated to make more conscious attempts to prescribe antibiotics appropriately if it is proven that judicious prescribing of antibiotics has positive impacts on treatment outcomes. The objective of this study was to determine the impact of appropriate prescribing of antibiotics on treatment outcomes, days of patient hospitalization and costs related to antibiotic treatment. Observational data on antibiotic treatment were collected for a one-month period from case notes of all inpatients (n=307) and outpatients (n=865) at five government and mission hospitals in Lesotho. Prescriptions were classified into categories of appropriateness based on extents to which antibiotics were prescribed according to principles. Treatment success rates, mean days of hospitalization and costs of antibiotic treatments of inpatients treated with specified prescription categories were determined. Appropriate prescribing of antibiotics for inpatients had positive impacts on treatment outcomes, patients’ days of hospitalization for infections and costs of antibiotic treatments. In outpatient settings, appropriate prescribing of antibiotics failed to show any significant impact on costs of antibiotics. Appropriate prescribing of antibiotics had a positive impact on patients’ recovery and costs of antibiotic treatments in inpatient settings.
Morrison, Paul; Meehan, Tom; Stomski, Norman Jay
The present study explores people's experience of living with antipsychotic medication side-effects. Qualitative data were gathered through semistructured interviews with 10 mental health consumers in a community care setting in Australia. The interview transcriptions were content analysed, and enhanced by combining manifest and latent content. Important contextual cues were identified through replaying the audio-recordings. Several main themes emerged from the analysis, including the impact of side-effects, attitudes to the use of medication and side-effects, and coping strategies to manage medication side-effects. Each participant reported between six and seven side-effects on average, which were often pronounced and had a major disruptive impact on their lives. Of these effects, the most commonly mentioned was sedation, which the participants described as leaving them in a 'zombie'-like state. Most participants expressed an attitude of acceptance about the side-effects. The participants' most common strategy to manage side-effects was to change the dosage of the medication. Other common side-effect management strategies involved using other medications to control side-effects, and diverse self-help techniques, the most common of which was relaxation/distraction techniques.
Silva, Maria das Dores Graciano; Rosa, Mário Borges; Franklin, Bryony Dean; Reis, Adriano Max Moreira; Anchieta, Lêni Márcia; Mota, Joaquim Antônio César
OBJECTIVE: To analyze the prevalence and types of prescribing and dispensing errors occurring with high-alert medications and to propose preventive measures to avoid errors with these medications. INTRODUCTION: The prevalence of adverse events in health care has increased, and medication errors are probably the most common cause of these events. Pediatric patients are known to be a high-risk group and are an important target in medication error prevention. METHODS: Observers collected data on prescribing and dispensing errors occurring with high-alert medications for pediatric inpatients in a university hospital. In addition to classifying the types of error that occurred, we identified cases of concomitant prescribing and dispensing errors. RESULTS: One or more prescribing errors, totaling 1,632 errors, were found in 632 (89.6%) of the 705 high-alert medications that were prescribed and dispensed. We also identified at least one dispensing error in each high-alert medication dispensed, totaling 1,707 errors. Among these dispensing errors, 723 (42.4%) content errors occurred concomitantly with the prescribing errors. A subset of dispensing errors may have occurred because of poor prescription quality. The observed concomitancy should be examined carefully because improvements in the prescribing process could potentially prevent these problems. CONCLUSION: The system of drug prescribing and dispensing at the hospital investigated in this study should be improved by incorporating the best practices of medication safety and preventing medication errors. High-alert medications may be used as triggers for improving the safety of the drug-utilization system. PMID:22012039
Richardson, Julie; Wishart, Laurie; Hanna, Steven
ABSTRACT Purpose: The purpose of this article is to apply theoretical frameworks to adherence behaviour and to guide the development of an intervention to increase adherence to prescribed home programmes. Summary of Key Points: Delivering an effective intervention requires establishing one that is evidence based and of adequate dosage. Two-thirds of patients who receive home exercise prescriptions do not adhere to their home programme, which may contribute to their physiotherapy's being ineffective. The mediating concepts of self-efficacy (SE) and outcome expectations (OE) are common to the five relevant theories used to explain adherence to exercise: the health belief model, protection motivation theory, theory of reasoned action, theory of planned behaviour, and social cognitive theory. Conclusion/Recommendations: Few intervention studies with any theoretical underpinning have examined adherence to exercise. Even fewer have been designed to affect and measure change in the theoretical mediators of SE and OE in patient populations. Physiotherapists must consider increasing adherence as a component of effective physiotherapy. Ongoing research is needed to increase our understanding of adherence to prescribed home programmes and to design interventions to affect theoretical mediators for increasing adherence. PMID:20190989
Celada, Pau; Lladó-Pelfort, Laia; Santana, N; Kargieman, L; Troyano-Rodriguez, Eva; Riga, M S; Artigas, Francesc
Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT(2A) receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.
Prescribed burning is highly uncommon in the Netherlands, where wildfire awareness is increasing but its risk management does not yet include fuel management strategies. A major exception is on two military bases, that need to burn their fields in winter and spring to prevent wildfires during summer shooting practice. Research on these very frequent burns has so far been limited to effects on biodiversity, yet site managers and policy makers have questions regarding the soil temperatures reached during these burns because of potential impact on soil properties and soil dwelling fauna. In March 2015, I therefore measured soil and litter temperatures under heath and grass vegetation during a prescribed burn on military terrain in the Netherlands. Soil and litter moisture were sampled pre- and post-fire, ash was collected, and fireline intensity was estimated from flame length. While standing vegetation was dry (0.13 g water/g biomass for grass and 0.6 g/g for heather), soil and litter were moist (0.21 cm3/cm3 and 1.6 g/g, respectively). Soil heating was therefore very limited, with maximum soil temperature at the soil-litter interface remaining being as low as 6.5 to 11.5°C, and litter temperatures reaching a maximum of 77.5°C at the top of the litter layer. As a result, any changes in physical properties like soil organic matter content and bulk density were not significant. These results are a first step towards a database of soil heating in relation to fuel load and fire intensity in this temperate country, which is not only valuable to increase understanding of the relationships between fire intensity and severity, but also instrumental in the policy debate regarding the sustainability of prescribed burns.
... fullstory_163655.html Docs More Likely to Prescribe Antibiotics If Patients Expect Them Study found physicians might ... HealthDay News) -- Doctors are more likely to prescribe antibiotics if they think patients expect the drugs, a ...
Klein, Lawrence E.; And Others
Physicians in an experimental group were surveyed to assess their knowledge of the effectiveness, cost, and side effects of antibiotics, and a tutorial was developed to modify some prescribing patterns. Prescribing patterns were statistically different. (Author/MLW)
... section, unless otherwise indicated— Certified electronic health record technology means an electronic... electronic prescribing technology by eligible professionals. Eligible professional means any of the following healthcare professionals who have prescribing authority: (i) A physician. (ii) A practitioner described...
... section, unless otherwise indicated— Certified electronic health record technology means an electronic... electronic prescribing technology by eligible professionals. Eligible professional means any of the following healthcare professionals who have prescribing authority: (i) A physician. (ii) A practitioner described...
... 162364.html U.S. Doctors Still Over-Prescribing Drugs: Survey More than 1 in 4 say antibiotics are ... doctors are still prescribing these treatments, a new survey of doctors reveals. Antibiotics are by far the ...
Fındıklı, Ebru; Gökçe, Mustafa; Nacitarhan, Vedat; Camkurt, Mehmet Akif; Fındıklı, Hüseyin Avni; Kardaş, Selçuk; Şahin, Merve Coşgun; Karaaslan, Mehmet Fatih
Objective That treatment with second-generation antipsychotics (SGAs) causes metabolic side effects and atherosclerosis in patients with schizophrenia and bipolar disorder (BD) is well-known. Increased arterial stiffness is an important marker of arteriosclerosis and has been identified as an independent risk factor for cardiovascular diseases. We measured pulse wave velocity (PWV) as a marker of arteriosclerosis in patients with schizophrenia and BD who use SGAs. Methods Patients and controls were collected from our psychiatry outpatient clinics or family medicine. Mental illness was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Mean age, gender, systolic and diastolic blood pressure, body mass index, Framingham risk score (FRS), etc. were determined. Simultaneous electrocardiography and pulse wave were recorded with an electromyography device. The photo-plethysmographic method was used to record the pulse wave. Inclusion criteria included use of SGAs for at least the last six months. Patients with diseases that are known to cause stiffness and the use of typical antipsychotics were excluded. Results Ninety-six subject (56 patients, 40 controls) were included in our study. There were 49 females, 47 males. Patients had schizophrenia (n=17) and BD (n=39). Their treatments were quetiapine (n=15), risperidone (n=13), olanzapine (n=15), and aripiprazole (n=13). Although differences in mean age, gender, and FRS in the patient and control groups were not statistically significant (p=1), PWV was greater in patients in the antipsychotic group (p=0.048). Conclusion This study supported the liability to stiffness in patients with schizophrenia and BD. Using SGAs may contribute to arterial stiffness in these patients. PMID:27776389
Maddali Bongi, S; Del Rosso, A
Physical exercise, aiming to improve range of movement, muscle strength and physical well being, lately substituted the immobilization previously prescribed in rheumatic diseases. International guidelines, recommendations of Scientific Societies, and structured reviews regard physical exercise as of pivotal importance in treating rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, fibromyalgia syndrome, osteoporosis, and to be considered in connective tissue diseases. Therapeutic exercise should: aim to improve firstly local symptoms and then general health; respect the pain threshold; be a part of a treatment including pharmacological therapies and other rehabilitation techniques, be administered by skilled physiotherapist under the guide of a rheumatologist, be different according to different diseases, disease phases and patient expectations.
Sloan, John P.
Current recommendations for prescribing for the frail elderly can be supplemented by others of value to family physicians. Minimization or simplification of medication regimens, proof of medication efficacy, vigilance for adverse drug reactions, and knowledge of aging and medications are important. Compliance is critical for the community-dwelling frail elderly but is rarely a problem in long-term care facilities. High-yield, high-risk conditions with presentations different from the “geriatric giants” must be recognized. Less medication is not necessarily the best treatment. Routine surveillance and frequent follow up are essential to adequate pharmacotherapy of frail elderly people. PMID:21221302
Karas, Albert; Kuehl, Bonnie
Hospital formularies, guided by the Pharmacy and Therapeutics Committee, exist to optimize medication use by identifying and designating drugs of choice to guide rational prescribing, ultimately reducing patient risk and costs and improving patient outcomes. Guidelines and a framework exist to guide critical evaluations of medications for formulary listing; however, there may be opportunities to improve and standardize how a formulary change could be instituted in Canadian hospitals. A formulary change at an Ontario hospital revealed that there are some key challenges to the formulary change process including the importance of a robust project plan, appropriate resources, healthcare staff education, and acceptance.
Leo, Raphael J.; Regno, Paula Del
Atypical antipsychotics are a class of novel agents increasingly employed for the treatment of psychotic disorders. The pharmacodynamic properties of the atypicals appear to impact a broader spectrum of psychotic symptoms than had been appreciated with older generation antipsychotics. In addition, the atypical agents appear to have a reduced risk of neurologic side effects compared with conventional antipsychotic use. Both of these features enhance the appeal of the atypical antipsychotics and may be associated with enhanced patient compliance. The atypical antipsychotics appear to be effective for schizophrenia as well as other psychotic disorders, including schizoaffective disorder and mood disorders with psychotic features. Consequently, atypical antipsychotics are now considered to be the first-line treatment for schizophrenia, with the exception of clozapine, which is considered a second-line agent because of risks associated with its use. This review will discuss the literature on atypical antipsychotic efficacy in psychotic disorders. Issues related to antipsychotic use, dosing, adverse effects, and drug interactions are also discussed. PMID:15014629
Stip, Emmanuel; Mancini-Marie, Adham
Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…
Ruiz, Lisa M.; Damron, Mackenzie; Jones, Kyle B.; Weedon, Dean; Carbone, Paul S.; Bakian, Amanda V.; Bilder, Deborah A.
This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4%) were taking antipsychotics, which was associated with male gender (p = 0.01), intellectual disability with and without autism…
Patel, Nick C.; Crismon, M. Lynn; Hoagwood, Kimberly; Johnsrud, Michael T.; Rascati, Karen L.; Wilson, James P.; Jensen, Peter S.
Objective: To estimate prevalence rates of antipsychotic use in children and adolescents from 1996 to 2001 in three state Medicaid programs (midwestern [MM], southern [SM], and western [WM]) and one private managed care organization (MCO). Method: Prescription claims were used to evaluate antipsychotic prevalence, defined as the number of children…
Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N
Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia.
Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh
Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.
Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh
Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837
Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.
Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…
Buckley, Peter F; Miller, Del D; Singer, Beth; Arena, John; Stirewalt, Edna M
There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.
Rutherford, Bret R; Pott, Emily; Tandler, Jane M.; Wall, Melanie M.; Roose, Steven P.; Lieberman, Jeffrey A.
Importance Because rising placebo response decreases drug-placebo differences and increases failed trials, it is imperative to determine what is causing this trend. Objective We investigated the relationships of antipsychotic medication/placebo response with publication year and identified associated study design and implementation variables. Data Sources Medline, PsycINFO, and PubMed were searched in July 2013 to identify randomized controlled trials (RCTs) of antipsychotic medications published from 1960-present. Study Selection Included were RCTs lasting 4–24 weeks, contrasting antipsychotic medication with placebo or active comparator, and enrolling patients ≥18 years with schizophrenia or schizoaffective disorder. Data Extraction and Synthesis Standardized mean change scores were calculated for each treatment cell, plotted against publication year, and tested with Spearman rank-order correlation coefficients. Hierarchical linear modeling identified factors associated with the standardized mean change across medication and placebo treatment cells. Main Outcome Measure We hypothesized that the mean change in placebo-treated patients would significantly increase from 1960-present, that greater change would be observed in active comparator vs. placebo-controlled trials, and that more protocol visits would increase the symptom change observed. Results In 106 trials examined, the mean change observed in placebo cells increased significantly with year of publication (N = 39, r = 0.52, p = 0.001), while the mean change in effective dose medication cells decreased significantly (N = 208, r = −0.26, p < 0.001). Significant interactions were found between assignment to effective dose medication and publication year (t = −5.55, df 260, p < 0.001), baseline severity (t = 5.08, df 260, p < 0.001), and study duration (t = −3.76, df 260, p < 0.001), indicating that the average drug-placebo difference significantly decreased over time, with decreasing baseline
Harries, C. S.; Botha, J.
When final year medical students reporting poor prescribing confidence were tested, key prescribing weaknesses emerged. This study aimed to characterize student variability in both the experience of and cognitive levels displayed during prescribing. Blooms Taxonomy cognitive categories were assigned to each question of a student test measuring…
... AFFAIRS 38 CFR Part 17 RIN 2900-AO77 Medications Prescribed by Non-VA Providers AGENCY: Department of... that eligible veterans engaged in current and future conflicts receive medications prescribed by non-VA... comply with a statutory mandate that VA provide medications prescribed by non-VA providers to...
Naber, Dieter; Lambert, Martin; Karow, Anne
Since the introduction of atypical antipsychotics success criteria of an effective antipsychotic treatment are more comprehensive. For instance these criteria include negative symptoms as well as cognitive deficits which are both important for the long-term prognosis of schizophrenia. However, the most fundamental change was the inclusion of the patients' perspective with respect to the treatment. Quality of life assessments as well as evaluation of subjective well-being are of increasing scientific interest and have been assessed in numerous studies. Accordingly there has been ascertained that schizophrenic patients are indeed able to fill out self reports consistently and reliably and it has been shown that patients' perspective differs enormously from the evaluation of psychiatrists with regard to antipsychotic treatment. In consideration of the variety of atypical antipsychotics and different resulting effects for compliance and prognosis of schizophrenia it seems needful to strengthen patients' perspective as an important success criterion of antipsychotic treatment.
Lee, Edwin; Chow, Lai-Yin; Leung, Chi-Ming
The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics.
LIEBERMAN, JEFFREY A.; BYMASTER, FRANK P.; MELTZER, HERBERT Y.; DEUTCH, ARIEL Y.; DUNCAN, GARY E.; MARX, CHRISTINE E.; APRILLE, JUNE R.; DWYER, DONARD S.; LI, XIN-MIN; MAHADIK, SAHEBARAO P.; DUMAN, RONALD S.; PORTER, JOSEPH H.; MODICA-NAPOLITANO, JOSEPHINE S.; NEWTON, SAMUEL S.; CSERNANSKY, JOHN G.
Various lines of evidence indicate the presence of progressive pathophysiological processes occurring within the brains of patients with schizophrenia. By modulating chemical neurotransmission, anti-psychotic drugs may influence a variety of functions regulating neuronal resilience and viability and have the potential for neuroprotection. This article reviews the current literature describing preclinical and clinical studies that evaluate the efficacy of antipsychotic drugs, their mechanism of action and the potential of first- and second-generation antipsychotic drugs to exert effects on cellular processes that may be neuroprotective in schizophrenia. The evidence to date suggests that although all antipsychotic drugs have the ability to reduce psychotic symptoms via D2 receptor antagonism, some antipsychotics may differ in other pharmacological properties and their capacities to mitigate and possibly reverse cellular processes that may underlie the pathophysiology of schizophrenia. PMID:18922967
Lieberman, Jeffrey A; Bymaster, Frank P; Meltzer, Herbert Y; Deutch, Ariel Y; Duncan, Gary E; Marx, Christine E; Aprille, June R; Dwyer, Donard S; Li, Xin-Min; Mahadik, Sahebarao P; Duman, Ronald S; Porter, Joseph H; Modica-Napolitano, Josephine S; Newton, Samuel S; Csernansky, John G
Various lines of evidence indicate the presence of progressive pathophysiological processes occurring within the brains of patients with schizophrenia. By modulating chemical neurotransmission, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and have the potential for neuroprotection. This article reviews the current literature describing preclinical and clinical studies that evaluate the efficacy of antipsychotic drugs, their mechanism of action and the potential of first- and second-generation antipsychotic drugs to exert effects on cellular processes that may be neuroprotective in schizophrenia. The evidence to date suggests that although all antipsychotic drugs have the ability to reduce psychotic symptoms via D(2) receptor antagonism, some antipsychotics may differ in other pharmacological properties and their capacities to mitigate and possibly reverse cellular processes that may underlie the pathophysiology of schizophrenia.
Babkin, Petr; George Thompson, Alayna M; Iancu, Cristina V; Walters, D Eric; Choe, Jun-Yong
The antipsychotic drug olanzapine is widely prescribed to treat schizophrenia and other psychotic disorders. However, it often causes unwanted side effects, including diabetes, due to disruption of insulin-dependant glucose metabolism through a mechanism yet to be elucidated. To determine if olanzapine can affect the first step in glucose metabolism - glucose transport inside cells - we investigated the effect of this drug on the transport activity of a model glucose transporter. The glucose transporter from Staphylococcus epidermidis (GlcPSe) is specific for glucose, inhibited by various human glucose transporter (GLUT) inhibitors, has high sequence and structure homology to GLUTs, and is readily amenable to transport assay, mutagenesis, and computational modeling. We found that olanzapine inhibits glucose transport of GlcPSe with an IC50 0.9 ± 0.1 mM. Computational docking of olanzapine to the GlcPSe structure revealed potential binding sites that were further examined through mutagenesis and transport assay to identify residues important for olanzapine inhibition. These investigations suggest that olanzapine binds in a polar region of the cytosolic part of the transporter, and interacts with residues R129, strictly conserved in all GLUTs, and N136, conserved in only a few GLUTs, including the insulin-responsive GLUT4. We propose that olanzapine inhibits GlcPSe by impeding the alternating opening and closing of the substrate cavity necessary for glucose transport. It accomplishes this by disrupting a key salt bridge formed by conserved residues R129 and E362, that stabilizes the outward-facing conformation of the transporter.
Leijon, ME; Bendtsen, P; Nilsen, P; Ekberg, K; Ståhle, A
Background Over the past decade, practitioners in primary health care (PHC) settings in many countries have issued written prescriptions to patients to promote increased physical activity or exercise. The aim of this study is to describe and analyse a comprehensive physical activity referral (PAR) scheme implemented in a routine PHC setting in Östergötland County. The study examines characteristics of the PARs recipients and referral practitioners, identifies reasons why practitioners opted to use PARs with their clients, and discusses prescribed activities and prescriptions in relation to PHC registries. Methods Prospective prescription data were obtained for 90% of the primary health care centres in Östergötland County, Sweden, in 2004 and 2005. The study population consisted of patients who were issued PARs after they were deemed likely to benefit from increased physical activity, as assessed by PHC staff. Results During the two-year period, a total of 6,300 patients received PARs. Two-thirds of the patients were female and half of the patients were 45–64 years. Half of the patients (50.8%) who received PARs were recommended a home-based activity, such as walking. One third (33%) of the patients issued PARs were totally inactive, reporting no days of physical activity that lasted for 30 minutes, and 29% stated that they reached this level 1–2 days per week. The number of PARs prescribed per year in relation to the number of unique individuals that visited primary health care during one year was 1.4% in 2004 and 1.2% in 2005. Two-thirds of the combined prescriptions were issued by physicians (38%) and nurses (31%). Physiotherapists and behavioural scientists issued the highest relative number of prescriptions. The most common reasons for issuing PARs were musculoskeletal disorders (39.1%) and overweight (35.4%), followed by high blood pressure (23.3%) and diabetes (23.2%). Conclusion Östergötland County's PAR scheme reached a relatively high proportion
McLellan, Lucy; Yardley, Sarah; Norris, Ben; de Bruin, Anique; Tully, Mary P.; Dornan, Tim
Prescribing tasks, which involve pharmacological knowledge, clinical decision-making and practical skill, take place within unpredictable social environments and involve interactions within and between endlessly changing health care teams. Despite this, curriculum designers commonly assume them to be simple to learn and perform. This research used…
... regulatory activities in the private radio, mass media, common carrier, and cable television services. ... fees. 1.1151 Section 1.1151 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND... section 9 of the Communications Act, 47 U.S.C. 159, which directs the Commission to prescribe and...
Delany, Clare; Kosta, Lauren; Ewen, Shaun; Nicholson, Patricia; Remedios, Louisa; Harms, Louise
With the globalisation of university education, national frameworks are commonly used to prescribe standardised learning outcomes and achieve accountability. However, these frameworks are generally not accompanied by guiding pedagogy to support academics in adjusting their teaching practices to achieve the set outcomes. This paper reports the…
Royal, Kenneth D.; Guskey, Thomas R.
A common practice in medical education is to create a prescribed distribution of grades, or ratings, so that only a certain percentage of students receive the highest marks. This approach typically is employed to curb grade inflation and as a means to help faculty distinguish outstanding performers. Despite the well-intentioned reasoning for using…
Salmon, J. Warren; Jiang, Ruixuan
Electronic-Prescribing, Computerized Prescribing, or E-RX has increased dramatically of late in the American health care system, a long overdue alternative to the written form for the almost five billion drug treatments annually. This paper examines the history and selected issues in the rise of E-RX by a review of salient literature, interviews, and field observations in Pharmacy. Pharmacies were early adopters of computerization for a variety of factors. The profession in its new corporate forms of chain drug stores and pharmacy benefits firms has sought efficiencies, profit enhancements, and clinical improvements through managed care strategies that rely upon data automation. E-RX seems to be a leading factor in overall physician acceptance of Electronic Medical Records (EMRs), although the Centers for Medicare and Medicaid (CMS) incentives seem to be the propelling force in acceptance. We conclude that greater research should be conducted by public health professionals to focus on resolutions to pharmaceutical use, safety, and cost escalation, which persist and remain dire following health reform. PMID:23569654
Flores, C.; Bounds, D.L.; Ruby, D.E.
The effects of fire on wetland vegetation in the mid-Atlantic region of the United States are poorly known, despite the historical use of fire by federal, state, and private landowners in the Chesapeake Bay Region. Prescribed fire is widely used by land managers to promote vegetation that is beneficial to migratory waterfowl, muskrats, and other native wildlife and to reduce competition from less desirable plant species. We compared vegetative response to two fire rotations, annual burns and 3-year burns, and two control sites, Control 1 and Control 2. We tested the effects of fire within six tidal marsh wetlands at Blackwater National Wildlife Refuge and Fishing Bay Wildlife Management Area in Maryland. We examined changes in total live biomass (all species), total stem density, litter, and changes in live biomass and stem density of four dominant wetland plant species (11 variables). Our results suggest that annual prescribed fires will decrease the accumulation of litter, increase the biomass and stem densities of some wetland plants generally considered less desirable for wildlife, and have little or no effect on other wetland plants previously thought to benefit from fire. ?? 2011 US Government.
Background Prescribing is a core activity for general practitioners, yet significant variation in the quality of prescribing has been reported. This suggests there may be room for improvement in the application of the current best research evidence. There has been substantial investment in technologies and interventions to address this issue, but effect sizes so far have been small to moderate. This suggests that prescribing is a decision-making process that is not sufficiently understood. By understanding more about prescribing processes and the implementation of research evidence, variation may more easily be understood and more effective interventions proposed. Methods An ethnographic study in three Scottish general practices with diverse organizational characteristics. Practices were ranked by their performance against Audit Scotland prescribing quality indicators, incorporating established best research evidence. Two practices of high prescribing quality and one practice of low prescribing quality were recruited. Participant observation, formal and informal interviews, and a review of practice documentation were employed. Results Practices ranked as high prescribing quality consistently made and applied macro and micro prescribing decisions, whereas the low-ranking practice only made micro prescribing decisions. Macro prescribing decisions were collective, policy decisions made considering research evidence in light of the average patient, one disease, condition, or drug. Micro prescribing decisions were made in consultation with the patient considering their views, preferences, circumstances and other conditions (if necessary). Although micro prescribing can operate independently, the implementation of evidence-based, quality prescribing was attributable to an interdependent relationship. Macro prescribing policy enabled prescribing decisions to be based on scientific evidence and applied consistently where possible. Ultimately, this influenced prescribing
Charron, Alexandra; Hage, Cynthia El; Servonnet, Alice; Samaha, Anne-Noël
Antipsychotic treatment can produce supersensitivity to dopamine receptor stimulation. This compromises the efficacy of ongoing treatment and increases the risk of relapse to psychosis upon treatment cessation. Serotonin 5-HT2 receptors modulate dopamine function and thereby influence dopamine-dependent responses. Here we evaluated the hypothesis that 5-HT2 receptors modulate the behavioural expression of antipsychotic-induced dopamine supersensitivity. To this end, we first treated rats with the antipsychotic haloperidol using a clinically relevant treatment regimen. We then assessed the effects of a 5-HT2 receptor antagonist (ritanserin; 0.01 and 0.1mg/kg) and of a 5-HT2A receptor antagonist (MDL100,907; 0.025-0.1mg/kg) on amphetamine-induced psychomotor activity. Antipsychotic-treated rats showed increased amphetamine-induced locomotion relative to antipsychotic-naïve rats, indicating a dopamine supersensitive state. At the highest dose tested (0.1mg/kg for both antagonists), both ritanserin and MDL100,907 suppressed amphetamine-induced locomotion in antipsychotic-treated rats, while having no effect on this behaviour in control rats. In parallel, antipsychotic treatment decreased 5-HT2A receptor density in the prelimbic cortex and nucleus accumbens core and increased 5-HT2A receptor density in the caudate-putamen. Thus, activation of either 5-HT2 receptors or of 5-HT2A receptors selectively is required for the full expression of antipsychotic-induced dopamine supersensitivity. In addition, antipsychotic-induced dopamine supersensitivity enhances the ability of 5-HT2/5-HT2A receptors to modulate dopamine-dependent behaviours. These effects are potentially linked to changes in 5-HT2A receptor density in the prefrontal cortex and the striatum. These observations raise the possibility that blockade of 5-HT2A receptors might overcome some of the behavioural manifestations of antipsychotic-induced dopamine supersensitivity.
Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa
Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (<80 years) (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.36-2.15]), male sex (OR, 1.52; CI, 1.21-1.91), history of psychiatric disorder (OR, 3.25; CI, 2.54-4.15), and inversely associated with Charlson Comorbidity Index score (score 1: OR, 0.74; CI, 0.57-0.97; score ≥2: OR, 0.68; CI, 0.47-0.97). In conclusion, the majority of persons with AD used antipsychotics with low or medium dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics, which indicates a need for precise dosing instructions in the treatment of behavioral and psychological symptoms of dementia. Clinicians should regularly assess dosing levels especially among men and those with history of psychiatric disorder.
Antipsychotic sensitization and tolerance refer to the increased and decreased drug effects due to past drug use, respectively. Both effects reflect the long-term impacts of antipsychotic treatment on the brain and result from the brain’s adaptive response to the foreign property of the drug. In this review, clinical evidence of the behavioral aspect of antipsychotic sensitization and tolerance is selectively reviewed, followed by an overview of preclinical literature that examines these behavioral characteristics and the related pharmacological and nonpharmacological factors. Next, recent work on the developmental impacts of adolescent antipsychotic sensitization and tolerance is presented and recent research that delineates the neurobiological mechanisms of antipsychotic sensitization and tolerance is summarized. A theoretical framework based on “drug learning and memory” principles is proposed to account for the phenomena of antipsychotic sensitization and tolerance. It is maintained that antipsychotic sensitization and tolerance follow basic principles of learning or acquisition (“induction”) and memory (“expression”). The induction and expression of both effects reflect the consequences of associative and nonassociative processing and are strongly influenced by various pharmacological, environmental, and behavioral factors. Drug-induced neuroplasticity, such as functional changes of striatal dopamine D2 and prefrontal serotonin (5-HT)2A receptors and their mediated signaling pathways, in principle, is responsible for antipsychotic sensitization and tolerance. Understanding the behavioral characteristics and neurobiological underpinnings of antipsychotic sensitization and tolerance has greatly enhanced our understanding of mechanisms of antipsychotic action, and may have important implications for future drug discovery and clinical practice. PMID:27371498
Wang, Jen-Yu; Wang, Cheng-Yi; Tan, Chen-Hui; Chao, Ting-Ting; Huang, Yung-Sung; Lee, Ching-Chih
Abstract The safety, tolerability, and efficacy data for antipsychotic drugs used in the acute phase of stroke are limited. The primary aim of this study was to examine the effectiveness and safety of typical and atypical antipsychotics on acute ischemic stroke mortality. This observational study was conducted in a retrospective cohort of patients selected from the 2010–2011 National Health Research Institute database in Taiwan. Patients were tracked for 1 month from the time of their first hospitalization for acute ischemic stroke. A nested case–control analysis was used to estimate the odds ratio (OR) of 30-day mortality associated with antipsychotic drug, adjusted for age, gender, disease severity, and comorbidities. The study cohort included 47,225 subjects with ischemic stroke, including 9445 mortality cases and 37,780 matched controls. After adjustment for the covariates, antipsychotics users before ischemic stroke are associated with a 73% decrease in the rate of mortality (OR 0.27; 95% CI 0.23–0.31). After ischemic stroke, the use of antipsychotics is associated with 87% decrease in the rate of mortality (OR 0.13; 95% CI 0.1–0.16). The users of conventional antipsychotics are associated with a 78% decrease in the rate of mortality (OR 0.22; 95% CI 0.18–0.26). The users of atypical antipsychotics are also associated with a 86% decrease in the rate of mortality (OR 0.14; 95% CI 0.12–0.17). We found that 1-month mortality among acute stroke patients treated with antipsychotics is significantly lower. The benefit on lower mortality was found not only among ischemic stroke patients who had received antipsychotics previously but also among patients who start antipsychotics after their stroke. PMID:25437033
Gordon, Stephen E.; Dufour, Alyssa B.; Monti, Sara M.; Mattison, Melissa L.P.; Catic, Angela G.; Thomas, Cindy P.; Lipsitz, Lewis A.
Objectives US nursing homes care for increasing numbers of residents with dementia and associated behavioral problems. They often lack access to specialized clinical expertise relevant to managing these problems. Project ECHO-AGE provides this expertise through videoconference sessions between frontline nursing home staff and clinical experts at an academic medical center. We hypothesized that ECHO-AGE would result in less use of physical and chemical restraints and other quality improvements in participating facilities. Design A 2:1 matched-cohort study comparing quality of care outcomes between ECHO-AGE facilities and matched controls for the period July 2012 to December 2013. Setting Eleven nursing homes in Massachusetts and Maine. Participants Nursing home staff and a hospital-based team of geriatrician, geropsychiatrist, and neurologist discussed anonymized residents with dementia. Intervention Biweekly online video case discussions and brief didactic sessions focused on the management of dementia and behavior disorders. Measurements The primary outcome variables were percentage of residents receiving antipsychotic medications and the percentage of residents who were physically restrained. Secondary outcomes included 9 other quality of care metrics from MDS 3.0. Results Residents in ECHO-AGE facilities were 75% less likely to be physically restrained compared with residents in control facilities over the 18-month intervention period (OR = 0.25, P = .05). Residents in ECHO-AGE facilities were 17% less likely to be prescribed antipsychotic medication compared with residents in control facilities (OR = 0.83, P = .07). Other outcomes were not significantly different. Conclusion Preliminary evidence suggests that participation in Project ECHO-AGE reduces rates of physical restraint use and may reduce rates of antipsychotic use among long-term nursing home residents. PMID:27161317
Henderson, Catherine; Knapp, Martin; Yeeles, Ksenija; Bremner, Stephen; Eldridge, Sandra; David, Anthony S.; O’Connell, Nicola; Burns, Tom; Priebe, Stefan
Background Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5% at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration ISRCTN.com 77769281 PMID:26448540
Rico-Villademoros, F; Calandre, E P; Slim, M
The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.
Olajossy-Hilkesberger, Luiza; Godlewska, Beata; Marmurowska-Michałowskal, Halina; Olajossy, Marcin; Landowski, Jerzy
Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.
Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.
Slim, Mahmoud; Medina-Caliz, Inmaculada; Gonzalez-Jimenez, Andres; Cabello, M Rosario; Mayoral-Cleries, Fermin; Lucena, M Isabel; Andrade, Raul J
The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs seems improved over that of chlorpromazine, they can occasionally cause idiosyncratic liver injury with varying phenotypes and, rarely, lead to acute liver failure. However, AAPs are a group of heterogeneous, chemically unrelated compounds with distinct pharmacological and pharmacokinetic properties and substantially different safety profiles, which precludes the notion of a class effect for hepatotoxicity risk and highlights the need for an individualized therapeutic approach. We discuss the current evidence on the hepatotoxicity potential of AAPs, the emerging underlying mechanisms, and the limitations inherent to this group of drugs for both establishing a proper causality assessment and developing strategies for risk management.
Brinkman, David; Disselhorst, Guus; Jansen, Bernard; Tichelaar, Jelle; van Agtmael, Michiel; de Vries, Theo; Richir, Milan
The aim of this study was to identify the information about commonly prescribed drugs that junior doctors should know in order to prescribe rationally in daily practice, defined as essential drug knowledge (EDK). A two-round Internet Delphi study was carried out involving general practitioners from one practice cluster, and registrars and consultants from two Dutch academic and eight teaching hospitals. A preliminary list of 377 potential EDK items for three commonly prescribed drugs was assessed on a dichotomous scale; an item was considered EDK if at least 80% consensus was reached. The consensus list of EDK items was discussed by the research team to identify similarities between the three drugs, with a view to forming a list of general EDK items applicable to other commonly prescribed drugs. Sixty experts considered 93 of the 377 items (25%) as EDK. These items were then used to form a list of 10 general EDK items. The list of EDK items identified by primary and secondary care doctors could be used in medical curricula and training programmes and for assessing the prescribing competence of future junior doctors. Further research is needed to evaluate the generalizability of this list for other commonly prescribed drugs.
Gallagher, J; McKeganey, N
There have been recent calls from within both Scotland and England for the wider prescription of heroin to heroin addicts as a way of coping with our burgeoning drug problem and as a route to reducing drug related criminality. But how feasible is heroin prescribing in this context? This paper considers some of the existing research evidence relating to heroin prescribing and looks also at the ethics and practicalities of prescribing heroin to heroin addicts in Scotland. We conclude that whilst the evidence on the benefits of heroin prescribing is far from clear cut there is a case for mounting a Scottish trial of heroin prescribing. Such a trial would need to be tightly controlled and rigorously evaluated. It would need to show that heroin prescribing was associated not only with a comparable level of harm reduction, as methadone prescribing, but that it was also an effective route towards drug users' eventual recovery and drug cessation.
Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry.
Wijma, Rixt A; van der Nagel, Bart C H; Dierckx, Bram; Dieleman, Gwen C; Touw, Daan J; van Gelder, Teun; Koch, Birgit C P
The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra-high performance liquid chromatography-mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra-high performance liquid chromatography-mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed-phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli-Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9-OH-risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run-time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.
Andrzejowski, Paul; Carroll, Will
Codeine is a drug that until recently was widely used in children. It was endorsed by the WHO as the second step on the analgesic ladder for cancer pain and has been used routinely for postoperative and breakthrough pain. Recently, its safety and efficacy have been called into question, following deaths after adenotonsillectomy was associated with its use. This has led to regulation by the US Food and Drug Administration, European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency to place significant restrictions on its use, and some centres have stopped using it altogether.In this article, we discuss the developmental pharmacology underpinning its action, reviewing what is known about the pharmacokinetics, pharmacodynamics and pharmacogenetics in children, how this relates to prescribing, as well as the practical issues and the recent regulatory framework surrounding its use.
Arnet, Isabelle; Hersberger, Kurt E
An important initial step in the medication process is prescription writing. The more perfect it is, the more successfully can a therapy be performed. Imprecisions and missing information lead to unnecessary queries or to errors which are often randomly discovered during a later consultation. A "perfect prescription" serves every individual involved in the medication process. The prescription document contains the instructions for the patient, the pharmacist, the nurse, and other health professionals involved in the therapy. The prescription writing process is regulated by several laws and decrees which were enacted to assure the greatest possible drug safety. Deviations from the norm may be necessary in individual cases, which require an even more responsible prescribing and explicit indication.
In this article, Dr. Andrew M. Kaunitz, associate professor of obstetrics and gynecology at the University of Florida Health Sciences Center in Jacksonville, gives suggestions for prescribing Depo-Provera. While Depo-Provera works as a contraceptive primarily by inhibiting ovulation, it has other antifertility effects, such as endometrial atrophy and cervical mucus thickening, which help prevent pregnancy in case ovulation does occur. A usual dose of Depo-Provera, 150 mg given intramuscularly every 3 months, has a contraceptive efficacy rate of 99.6%--the highest rate for any hormonal method. Kaunitz explains that the initial injection of the drug should take place within 7 days of the beginning of menses to ensure that there is no pregnancy. Efficacy is highest up to 12 weeks after injection, even though ovulation does not take place 14 weeks after the drug is administered. In the event that the patient is more than 2 weeks late in receiving her second or subsequent injection, Kaunitz recommends obtaining a pregnancy test. Because of possible adverse effects on carbohydrate metabolism and lipoprotein levels, Kaunitz suggests that women at high risk of cardiovascular disease or diabetes receive a lower dose of the drug, 100 mg. Similarly, very small women (those weighing under 100 lbs) may also require a smaller dose. Even at a lower dose, says Kaunitz, Depo-Provera remains highly effective, with a failure rate of 1%. Kaunitz also emphasizes prescribing Depo-Provera only to women who want a long-term contraceptive (at least 2 years), since although it does not affect fertility permanently, it does take longer for fertility to return than with oral contraceptives or Norplant.
Charlton, Rachel A.; Klungsøyr, Kari; Neville, Amanda J.; Jordan, Sue; Pierini, Anna; de Jong-van den Berg, Lolkje T. W.; Bos, H. Jens; Puccini, Aurora; Engeland, Anders; Gini, Rosa; Davies, Gareth; Thayer, Daniel; Hansen, Anne V.; Morgan, Margery; Wang, Hao; McGrogan, Anita; Nybo Andersen, Anne-Marie; Dolk, Helen; Garne, Ester
Aim To explore antidiabetic medicine prescribing to women before, during and after pregnancy in different regions of Europe. Methods A common protocol was implemented across seven databases in Denmark, Norway, The Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. Women with a pregnancy starting and ending between 2004 and 2010, (Denmark, 2004–2009; Norway, 2005–2010; Emilia Romagna, 2008–2010), which ended in a live or stillbirth, were identified. Prescriptions for antidiabetic medicines issued (UK) or dispensed (non-UK) during pregnancy and/or the year before or year after pregnancy were identified. Prescribing patterns were compared across databases and over calendar time. Results 1,082,673 live/stillbirths were identified. Pregestational insulin prescribing during the year before pregnancy ranged from 0.27% (CI95 0.25–0.30) in Tuscany to 0.45% (CI95 0.43–0.47) in Norway, and increased between 2004 and 2009 in all countries. During pregnancy, insulin prescribing peaked during the third trimester and increased over time; third trimester prescribing was highest in Tuscany (2.2%) and lowest in Denmark (0.5%). Of those prescribed an insulin during pregnancy, between 50.5% in Denmark and 88.8% in the Netherlands received an insulin analogue alone or in combination with human insulin, this proportion increasing over time. Oral products were mainly metformin and prescribing was highest in the 3 months before pregnancy. Metformin use during pregnancy increased in some countries. Conclusion Pregestational diabetes is increasing in many areas of Europe. There is considerable variation between and within countries in the choice of medication for treating pregestational diabetes in pregnancy, including choice of insulin analogues and oral antidiabetics, and very large variation in the treatment of gestational diabetes despite international guidelines. PMID:27192491
Friesen, Kevin J; Bugden, Shawn C
Background Citalopram is the most commonly prescribed antidepressant in Canada. Concerns have been raised about its cardiac safety, and a dose-dependent prolongation of the QT interval has been documented. Drug interactions involving concomitant use of other medications that prolong the QT interval or increase citalopram levels by interfering with its metabolism increase the cardiac risk. Regulatory bodies (Health Canada and the US Food and Drug Administration) issued warnings and required labeling changes in 2011/2012, suggesting maximum citalopram doses (<40 mg for those <65 years; <20 mg for those ≥65 years) and avoiding drug interactions that increase cardiac risk. The purpose of this study is to assess the impact of these warnings on citalopram prescribing practices. Methods A quasi-experimental interrupted time series analysis was conducted using all citalopram prescribing data from the population of Manitoba, Canada from 1999 to 2014. This allowed for the examination of high-dose prescribing (above regulatory warning levels) and the number of interacting medications per citalopram prescription. Results There was a dramatic decline in the prescribing of high doses in both age groups, with a 64.8% decline in those <65 years and 33.6% in those ≥65 years. Segmented regression models indicated significant breakpoints in the third quarter of 2011 for both age groups (P<0.0001), corresponding to the time the regulatory warnings were issued. There appeared to be no impact of the warnings on the prescribing of interacting medications. The number of interacting medications actually increased in the postwarning period (<65, 0.78–0.81 interactions per citalopram prescription; ≥65, 0.93–0.94, P<0.001). Conclusion Regulatory changes appear to have produced an important reduction in the high-dose prescribing of citalopram. In contrast to this relatively simple dosage change, there was no indication that the more complex issue of resolving drug–drug interactions
Kooiker, C. H.; Scutchfield, F. D.
From a questionnaire sent to all obstetricians and gynecologists and all family and general practitioners in San Diego County, California, regarding the Copper T 380A intrauterine device, substantial barriers to prescribing it were identified. Of all physicians responding, 40% reported that they were not recommending the Copper T 380A to anyone, the single most common reason given being concern about medical liability. A lack of knowledge about the new device, a lack of intrauterine device insertion skills, and certain medical practice settings were also important barriers to prescribing it. The new intrauterine device is considered in the context of innovation-diffusion theory. Substantial amounts of education and training and improvement in the medical-legal climate are needed before current barriers to prescribing the new device are removed. Images PMID:2219892
Rohleder, Cathrin; Müller, Juliane K.; Lange, Bettina; Leweke, F. M.
There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials. PMID:27877130
Haring, Liina; Vasar, Eero; Vasar, Veiko; Zilmer, Mihkel
38 first-episode psychosis (FEP) patients and 37 control subjects were recruited for the study of indices of oxidative stress (OxS). The main purpose of the study was to compare the OxS statuses (serum total antioxidant capacity (TAC), total level of peroxides (TPX), oxidative stress index (OSI), and ratio oxidized methionine (Met-SO) to methionine (Met)) between antipsychotic-naïve FEP patients and individuals without a history of psychiatric disorders. Subsequently, the impact of 7-month antipsychotic treatment was evaluated on the OxS status in FEP patients. An attempt was made to assess links between OxS signature and inflammation markers. The oxidative stress indices remained generally unchanged in antipsychotic-naïve FEP patients compared to control subjects. Despite that, there was a significant correlation between the levels of TPX and EGF (endothelial growth factor) in FEP patients. This correlation disappeared after antipsychotic treatment of FEP patients. Moreover, antipsychotic treatment was associated with a significant reduction in OxS indices, including TPX, OSI, and ratio between Met-SO and Met. By contrast, in chronic SCZ patients we established a significant high-grade OxS. In conclusion, the markers of total antioxidative capacity, lipid peroxidation, and protein oxidation revealed no high-grade OxS in FEP patients. Nevertheless, antipsychotic treatment induced a considerable anti-inflammatory effect. OxS levels were also significantly decreased if compared in FEP patients before and after antipsychotic treatment. PMID:27528889
Uchida, Takahito; Suzuki, Takefumi; Sakurai, Hitoshi; Tsutsumi, Chisa; Den, Ryosuke; Mimura, Masaru; Uchida, Hiroyuki
Long-term follow-up data of patients with schizophrenia on depot antipsychotics have been few and the longest follow-up period has been up to 7 years. We carried out a systematic chart review to examine 10-year outcomes for outpatients with schizophrenia who were receiving a conventional depot antipsychotic. Maintenance of outpatient status for 10 years was considered as a favorable outcome. From the initial sample of 1587 outpatients, 90 patients who were receiving a depot antipsychotic were included in this study (mean±SD, age 44.0±13.0 years; men, N=54). Haloperidol decanoate, fluphenazine decanoate, fluphenazine enanthate, and haloperidol decanoate plus fluphenazine enanthate were used in 53 (58.9%), 29 (32.2%), seven (7.8%), and one (1.1%) patients, respectively. These depot antipsychotics accounted for 36.9% of the total antipsychotic dosage on average. Seventeen patients (18.9%) successfully maintained outpatient status for 10 years. The most frequent reason for dropout was 'hospitalization' (N=49, 54.4%), followed by 'referral to another clinic/hospital' (N=9, 10.0%) and 'side effects' (N=7, 7.8%). As only 36.9% of the chlorpromazine equivalents were administered through depot antipsychotics, it is difficult to draw any firm conclusion. Still, the data suggest that even depot antipsychotics may not sufficiently prevent relapse in the treatment of schizophrenia.
Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E
Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.
Stevenson, J M; Reilly, J L; Harris, M S H; Patel, S R; Weiden, P J; Prasad, K M; Badner, J A; Nimgaonkar, V L; Keshavan, M S; Sweeney, J A; Bishop, J R
Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development. PMID:26905411
Attard, Azizah; Taylor, David M
Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials.
Sørensen, Merete Juul; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard; Vestergaard, Mogens; Christensen, Jacob; Olsen, Jørn; Parner, Erik; Pedersen, Lars Henning; Bech, Bodil Hammer
Background Antipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth. Methods In a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively. Results Women exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19). Conclusions The increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to
Background Schizophrenia is a severe form of mental illness which is associated with significant and long-lasting health, social and financial burdens. The aim of this project is to assess the efficiency of the antipsychotics used in Spain in reducing schizophrenia relapses under the Spanish Health System perspective. Material and methods A decision-analytic model was developed to explore the relative cost-effectiveness of five antipsychotic medications, amisulpride, aripiprazole, olanzapine, paliperidone Extended-Release (ER) and risperidone, compared to haloperidol, over a 1-year treatment period among people living in Spain with schizophrenia. The transition probabilities for assessed therapies were obtained from the systemic review and meta-analysis performed by National Institute for Health and Clinical Excellence (NICE). Results Paliperidone ER was the option that yielded more quality-adjusted life years (QALYs) gained per patient (0.7573). In addition, paliperidone ER was the least costly strategy (€3,062), followed by risperidone (€3,194), haloperidol (€3,322), olanzapine (€3,893), amisulpride (€4,247) and aripiprazole (€4,712). In the incremental cost-effectiveness (ICE) analysis of the assessed antipsychotics compared to haloperidol, paliperidone ER and risperidone were dominant options. ICE ratios for other medications were €23,621/QALY gained, €91,584/QALY gained and €94,558/QALY gained for olanzapine, amisulpride and aripiprazole, respectively. Deterministic sensitivity analysis showed that risperidone is always dominant when compared to haloperidol. Paliperidone ER is also dominant apart from the exception of the scenario with a 20% decrease in the probability of relapses. Conclusions Our findings may be of interest to clinicians and others interested in outcomes and cost of mental health services among patients with schizophrenia. Paliperidone ER and risperidone were shown to be dominant therapies compared to haloperidol in Spain
Tan, Hock Heng; Hoppe, Jason; Heard, Kennon
As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.
de Jong, Simone; Boks, Marco P M; Fuller, Tova F; Strengman, Eric; Janson, Esther; de Kovel, Carolien G F; Ori, Anil P S; Vi, Nancy; Mulder, Flip; Blom, Jan Dirk; Glenthøj, Birte; Schubart, Chris D; Cahn, Wiepke; Kahn, René S; Horvath, Steve; Ophoff, Roel A
Despite large-scale genome-wide association studies (GWAS), the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co-expression modules associated with schizophrenia. Several of these disease related modules are likely to reflect expression changes due to antipsychotic medication. However, two of the disease modules could be replicated in an independent second data set involving antipsychotic-free patients and controls. One of these robustly defined disease modules is significantly enriched with brain-expressed genes and with genetic variants that were implicated in a GWAS study, which could imply a causal role in schizophrenia etiology. The most highly connected intramodular hub gene in this module (ABCF1), is located in, and regulated by the major histocompatibility (MHC) complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes in this network.
Bakker, Ilse C A; Schubart, Chris D
Summary In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. Learning points Prolactinoma coinciding with psychosis can represent a therapeutic challenge. In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels. Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis. PMID:27284453
Roberts, David Leland; Penn, David Lewis; Corrigan, Patrick; Lipkovich, Ilya; Kinon, Bruce; Black, Ryan Andrew
Social cognition has received increased attention in schizophrenia research because it is associated with functional outcomes. Psychosocial interventions are being developed to enhance social cognition, however less attention has been paid to the association between antipsychotic medication use and social cognition. This study evaluated whether individuals treated with olanzapine (n=117) or quetiapine (n=106) achieved improvements in social cognition. Participants were drawn from a larger 6-month, multi-site, randomized, double-blind clinical trial. Social cognition was assessed using signal detection analysis of performance on the Social Cue Recognition Test. Social functioning was measured with an interpersonal functioning index and a broader quality of life measure. Results revealed that participants in both medication groups improved significantly but modestly on three out of four social cognition subscales. The small observed effect in this trial is generally consistent with previous studies, and supports the need for ongoing research into the biological mechanisms of social cognitive dysfunction in schizophrenia.
Hrdlicka, Michal; Dudova, Iva
Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226
Murdoch, J. C.
The total prescribing in an urban general practice was recorded over a six-month period and classified according to the length of time that drugs were continued. The number of patients receiving any prescription rose with age, as did the total number of items per patient prescribed for; while the continued items rose with age, the number of items prescribed once only per patient remained constant in all age groups. The bulk of the total prescribing was for the elderly and this was mainly for continued items. The classification also shows that certain drug groups are liable to be continued whereas others are virtually always prescribed once only. The implications of these findings for self-audit of prescribing and the care of the elderly in general practice are discussed. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7452600
Haddad, Peter M; Brain, Cecilia; Scott, Jan
Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness’s association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive
Background Major depressive disorder (MDD) is a debilitating and costly mental disorder. Although commercially available antidepressants have proliferated over the last 20 years, a substantial number of patients either do not respond adequately to these drugs or are unable to tolerate their adverse effects. One common approach has been to augment conventional antidepressants with an adjunctive agent, but the optimal selection of atypical antipsychotic agents for adjunctive treatment of treatment-resistant depression (TRD) remains controversial. Methods/Design An electronic literature search of PubMed, the Cochrane Library, Embase, Web of Science, LiLACS, CINAHL, and PsycINFO for studies will be conducted with no restrictions on language, publication year, or publication type. Several clinical trial registry agencies, pharmaceutical company websites, and FDA reports will also be reviewed. Randomized clinical trials (RCTs) with atypical antipsychotic augmentation treatment for treatment-resistant depression will be considered. Data will be independently extracted by two reviewers. Traditional pairwise meta-analyses will be performed for RCTs that directly compare different treatment arms. Then, Bayesian network meta-analyses will be performed to compare the relative efficacy and acceptability of different atypical antipsychotic agents (and doses). A sensitivity analysis will be performed by excluding studies classified as a small sample size, having a high placebo effect. Discussion This systematic review and network meta-analysis will comparatively analyze the efficacy, quality of life, and acceptability profiles of atypical antipsychotic medications used for the adjunctive treatment of TRD. The findings should provide clinically relevant implications for comprehensively understanding the risk–benefit profiles of these adjunctive treatments. Systematic review registration PROSPERO CRD 42014009666. PMID:25373601
Shin, J G; Soukhova, N; Flockhart, D A
The ability of antipsychotic drugs to inhibit the catalytic activity of five cytochrome P-450 (CYP) isoforms was compared using in vitro human liver microsomal preparations to evaluate the relative potential of these drugs to inhibit drug metabolism. The apparent kinetic parameters for enzyme inhibition were determined by nonlinear regression analysis of the data. All antipsychotic drugs tested competitively inhibited dextromethorphan O-demethylation, a selective marker for CYP2D6, in a concentration-dependent manner. Thioridazine and perphenazine were the most potent, with IC(50) values (2.7 and 1.5 microM) that were comparable to that of quinidine (0.52 microM). The estimated K(i) values for CYP2D6-catalyzing dextrorphan formation were ranked in the following order: perphenazine (0.8 microM), thioridazine (1.4 microM), chlorpromazine (6.4 microM), haloperidol (7.2 microM), fluphenazine (9.4 microM), risperidone (21.9 microM), clozapine (39.0 microM), and cis-thiothixene (65.0 microM). No remarkable inhibition of other CYP isoforms was observed except for moderate inhibition of CYP1A2-catalyzed phenacetin O-deethylation by fluphenazine (K(i) = 40.2 microM) and perphenazine (K(i) = 65.1). The estimated K(i) values for the inhibition of CYP2C9, 2C19, and 3A were >300 microM in almost all antipsychotics tested. These results suggest that antipsychotic drugs exhibit a striking selectivity for CYP2D6 compared with other CYP isoforms. This may reflect a remarkable commonality of structure between the therapeutic targets for these drugs, the transporters, and metabolic enzymes that distribute and eliminate them. Clinically, coadministration of these medicines with drugs that are primarily metabolized by CYP2D6 may result in significant drug interactions.
Context: Drug-drug interactions(DDIs) are significant but avoidable causes of iatrogenic morbidity and hospital admission. Aim: To detect potential drug-drug interactions among medications received by hypertensive patients. Materials and Methods: Patients of both sex and all adult age groups, who were attending medicine out -patient department (OPD) of a tertiary care teaching rural hospital since last six months and were being prescribed antihypertensive drug/s for essential hypertension, were selected for the study. Hypertensive patient with co-morbities diabetes mellitus, ischemic heart diseases, congestive heart failure, and chronic renal diseases were also included in the study. Potential drug drug interactions were checked with medscape drug interaction software. Results: With the help of medscape drug interaction software, 71.50% prescriptions were identified having atleast one drug-drug interaction. Total 918 DDIs were found in between 58 drug pairs. 55.23% DDIs were pharmacodynamic, 4.79% pharmacokinetic type of DDIs. 32.24% DDIs were found affecting serum potassium level. 95.42% DDIs were found significant type of DDIs. Drug drug interaction between atenolol & amlodipine was the most common DDI (136) followed by metoprolol and amlodine (88) in this study. Atenolol and amlodipine ( 25.92%) was the most common drugs to cause DDIs in our study. Conclusion: We detected a significant number of drug drug interaction in hypertensive patients. These interactions were between antihypertensive agents or between hypertensive and drug for co-morbid condition. PMID:25584241
Whitmire, Alexandra; Johnston, Smith; Lockley, Steven
The NASA Fatigue Management Team is developing recommendations for managing fatigue during travel and for shift work operations, as Clinical Practice Guidelines for the Management of Circadian Desynchrony in ISS Operations. The Guidelines provide the International Space Station (ISS ) flight surgeons and other operational clinicians with evidence-based recommendations for mitigating fatigue and other factors related to sleep loss and circadian desynchronization. As much international travel is involved both before and after flight, the guidelines provide recommendations for: pre-flight training, in-flight operations, and post-flight rehabilitation. The objective of is to standardize the process by which care is provided to crewmembers, ground controllers, and other support personnel such as trainers, when overseas travel or schedule shifting is required. Proper scheduling of countermeasures - light, darkness, melatonin, diet, exercise, and medications - is the cornerstone for facilitating circadian adaptation, improving sleep, enhancing alertness, and optimizing performance. The Guidelines provide, among other things, prescribed travel schedules that outline the specific implementation of these mitigation strategies. Each travel schedule offers evidence based protocols for properly using the NASA identified countermeasures for fatigue. This presentation will describe the travel implementation schedules and how these can be used to alleviate the effects of jet lag and/or schedule shifts.
Wang, Kai; Liu, Sheng; Chen, Fei; Qin, Zong; Liu, Zongyuan; Luo, Xiaobing
Freeform lenses are playing a more and more important role in LED secondary optics design. In this study, based on the new light energy mapping relationship, edge ray principle, Snell's law and error control of surface construction, a modified discontinuous freeform lens design method was presented for rectangularly prescribed illumination, with the advantages of a flexible energy mapping relationship, accurate light irradiation control and easier to manufacture. A polymethyl methacrylate (PMMA) discontinuous freeform lens was designed as an example for LED tunnel illumination according to this method. The numerical simulation results demonstrated that the light pattern of the lens was in good agreement with the expected illumination performance when using a point source. Tolerance analyses were also conducted. An extended light source had little effect on the light output efficiency (LOE) of the lens but significantly decreased the effective illumination area. Installation errors had more effect on the uniformity and shape of the light pattern than the LOE of the lens. The tolerances of vertical, horizontal and rotational deviation of this lens were 0.4 mm, 0.4 mm and 2°, respectively.
... nose, coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... avoid colds. There is no cure for the common cold. For relief, try Getting plenty of rest Drinking ...
Marienfeld, Carla Beth; Tek, Ece; Diaz, Esperanza; Schottenfeld, Richard; Chawarski, Marek
Psychiatrists' decision making about prescribing benzodiazepines (BZD) was evaluated in a community mental health center. An anonymous survey of outpatient psychiatrists in an academic-affiliated public mental health center was conducted using a 45-item questionnaire developed based on the results of a previous study. Sixty-six percent of responses indicate that, at times, psychiatrists experienced requests for behaviors suspicious for abuse, including 'lost/missing prescriptions' and 'use of BZD by others'. Patient characteristics such as 'history of abuse', 'unknown patient', and 'patient use of illicit substances' were occasional or common reasons for NOT prescribing BZDs (75%). The most common contexts in which the majority of our sample was uncomfortable prescribing BZDs involved a patient history of substance abuse, fear of initiation of dependence, diversion, and feeling manipulated by the patient. Time limitations were a dilemma for 20%. Psychiatrist self-reported dilemma and behavior in prescribing BZDs largely reflected concerns with substance abuse and less frequently workload or time issues.
van Mantgem, Philip J.; Nesmith, Jonathan C. B.; Keifer, MaryBeth; Brooks, Matthew
The reintroduction of fire to historically fire-prone forests has been repeatedly shown to reduce understory fuels and promote resistance to high severity fire. However, there is concern that prescribed fire may also have unintended consequences, such as high rates of mortality for large trees and fire-tolerant Pinus species. To test this possibility we evaluated mortality patterns for two common genera in the western US, Pinus and Abies, using observations from a national-scale prescribed fire effects monitoring program. Our results show that mortality rates of trees >50 DBH were similar for Pinus (4.6% yr-1) and Abies (4.0% yr-1) 5 years following prescribed fires across seven sites in the southwestern US. In contrast, mortality rates of trees >50 cm DBH differed between Pinus (5.7% yr-1) and Abies (9.0% yr-1). Models of post-fire mortality probabilities suggested statistically significant differences between the genera (after including differences in bark thickness), but accounting for these differences resulted in only small improvements in model classification. Our results do not suggest unusually high post-fire mortality for large trees or for Pinus relative to the other common co-occurring genus, Abies, following prescribed fire in the southwestern US.
Montejo, Ángel L; Arango, Celso; Bernardo, Miquel; Carrasco, José L; Crespo-Facorro, Benidicto; Cruz, Juan J; Del Pino-Montes, Javier; García-Escudero, Miguel A; García-Rizo, Clemente; González-Pinto, Ana; Hernández, Ana I; Martín-Carrasco, Manuel; Mayoral-Cleries, Fermín; Mayoral-van Son, Jaqueline; Mories, M Teresa; Pachiarotti, Isabella; Pérez, Jesús; Ros, Salvador; Vieta, Eduard
Hyperprolactinemia is an underappreciated/unknown adverse effects of antipsychotics. The consequences of hyperprolactinemia compromise therapeutic adherence and can be serious. We present the consensus recommendations made by a group of experts regarding the management of antipsychotic-induced hyperprolactinemia. The current consensus was developed in 3 phases: 1, review of the scientific literature; 2, subsequent round table discussion to attempt to reach a consensus among the experts; and 3, review by all of the authors of the final conclusions until reaching a complete consensus. We include recommendations on the appropriate time to act after hyperprolactinemia detection and discuss the evidence on available options: decreasing the dose of the antipsychotic drug, switching antipsychotics, adding aripiprazole, adding dopaminergic agonists, and other type of treatment. The consensus also included recommendations for some specific populations such as patients with a first psychotic episode and the pediatric-youth population, bipolar disorder, personality disorders and the elderly population.
... Associated with Off-Label Use of Atypical Antipsychotic Drugs Side effect Comment Death Rare, increased risk of death in ... the evidence on the effectiveness, safety, and adverse effects of the drugs included in this report. A team of physicians ...
Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo
Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180
Pompili, Maurizio; Baldessarini, Ross J; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo
Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior.
Awad, A George; Voruganti, Lakshmi N P
Schizophrenia is a long-term disabling illness that affects approximately 1% of the population. Its course is generally chronic with acute psychotic exacerbations that may require frequent hospitalisations. The clinical picture includes a range of symptoms such as delusions, hallucinations, agitation, suspiciousness, hostility, conceptual disorganisation, blunted affect, emotional and social withdrawal, lack of spontaneity, poverty of speech and a wide range of neurocognitive deficits. Over the past 50 years, antipsychotic medications have emerged as the cornerstone of management in concert with other important interventions, such as psychosocial and economic support and rehabilitation efforts. However, the unrivalled role of conventional antipsychotic medications has been continuously challenged by the wide range of adverse effects of these medications and their lack of usefulness in the treatment of neurocognitive deficits as well as deficit and negative symptoms. In addition, the lack of subjective tolerability of these agents and their negative impact on quality of life have complicated management for a large number of patients. Over the last 15 years, several new atypical antipsychotic medications have been introduced, including amisulpride, remoxipride, risperidone, sertindole, olanzapine, zotepine, quetiapine, ziprasidone and aripiprazole. In general, the new antipsychotics have shown themselves to be at least comparable in efficacy to conventional antipsychotics but with superior subjective tolerability and a more favourable adverse effect profile. The majority of quality of life studies involving new antipsychotic agents have evaluated the benefits of risperidone, olanzapine and clozapine; only a few studies have examined the effects of other new antipsychotics. While most of these studies have methodological and design limitations, the weight of evidence from them nevertheless points to a trend towards a more positive impact on quality of life with
Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance
Motulsky, Aude; Abrahamowicz, Michal; Eguale, Tewodros; Buckeridge, David L; Tamblyn, Robyn
Objective To examine off-label indications for antidepressants in primary care and determine the level of scientific support for off-label prescribing. Design Descriptive study of antidepressant prescriptions written by primary care physicians using an indication based electronic prescribing system. Setting Primary care practices in and around two major urban centres in Quebec, Canada. Participants Patients aged 18 years or older who visited a study physician between 1 January 2003 and 30 September 2015 and were prescribed an antidepressant through the electronic prescribing system. Main outcome measures Prevalence of off-label indications for antidepressant prescriptions by class and by individual drug. Among off-label antidepressant prescriptions, the proportion of prescriptions in each of the following categories was measured: strong evidence supporting use of the prescribed drug for the respective indication; no strong evidence for the prescribed drug but strong evidence supporting use of another drug in the same class for the indication; or no strong evidence supporting use of the prescribed drug and all other drugs in the same class for the indication. Results 106 850 antidepressant prescriptions were written by 174 physicians for 20 920 adults. By class, tricyclic antidepressants had the highest prevalence of off-label indications (81.4%, 95% confidence interval, 77.3% to 85.5%), largely due to a high off-label prescribing rate for amitriptyline (93%, 89.6% to 95.7%). Trazodone use for insomnia was the most common off-label use for antidepressants, accounting for 26.2% (21.9% to 30.4%) of all off-label prescriptions. For only 15.9% (13.0% to 19.3%) of all off-label prescriptions, the prescribed drug had strong scientific evidence for the respective indication. For 39.6% (35.7% to 43.2%) of off-label prescriptions, the prescribed drug did not have strong evidence but another antidepressant in the same class had strong evidence for the respective
Ivanova, S A; Smirnova, L P; Shchigoreva, Yu G; Semke, A V; Bokhan, N A
Serum concentrations of oxidized and reduced glutathione were measured in 73 patients with schizophrenia at admission and in dynamics of therapy with traditional and atypical antipsychotic drugs. The level of reduced glutathione in patients with schizophrenia with manifest clinical symptoms was lower than in normal subjects. Atypical neuroleptics produced virtually no effects on the glutathione system, while therapy with typical antipsychotics led to further decrease in the levels of reduced glutathione, thus aggravating the imbalance of metabolic processes typical of schizophrenia.
Holland, Greg J; Clarke, Michael F; Bennett, Andrew F
Prescribed burning to achieve management objectives is a common practice in fire-prone regions worldwide. Structural components of habitat that are combustible and slow to develop are particularly susceptible to change associated with prescribed burning. We used an experimental, "whole-landscape" approach to investigate the effect of differing patterns of prescribed burning on key habitat components (logs, stumps, dead trees, litter cover, litter depth, and understorey vegetation). Twenty-two landscapes (each ~100 ha) were selected in a dry forest ecosystem in southeast Australia. Experimental burns were conducted in 16 landscapes (stratified by burn extent) while six served as untreated controls. We measured habitat components prior to and after burning. Landscape burn extent ranged from 22% to 89% across the 16 burn treatments. With the exception of dead standing trees (no change), all measures of habitat components declined as a consequence of burning. The degree of loss increased as the extent to which a landscape was burned also increased. Prescribed burning had complex effects on the spatial heterogeneity (beta diversity) of structural components within landscapes. Landscapes that were more heterogeneous pre-fire were homogenized by burning, while those that were more homogenous pre-fire tended to display greater differentiation post-burning. Thus, the notion that patch mosaic burning enhances heterogeneity at the landscape-scale depends on prior conditions. These findings have important management implications. Where prescribed burns must be undertaken, effects on important resources can be moderated via control of burn characteristics (e.g., burn extent). Longer-term impacts of prescribed burning will be strongly influenced by the return interval, given the slow rate at which some structural components accumulate (decades to centuries). Management of habitat structural components is important given the critical role they play in (1) provision of habitat
Morgan, Steven G.; Hunt, Jordan; Rioux, Jocelyn; Proulx, Jeffery; Weymann, Deirdre; Tannenbaum, Cara
Background: Many medications pose greater health risks when prescribed for older adults, compared with available pharmacologic and nonpharmacologic alternatives. We sought to quantify the frequency and cost of potentially inappropriate prescribing for older women and men in Canada. Methods: Using data for 2013 from the National Prescription Drug Utilization Information System database, which contains prescription claims from publicly financed drug plans in all provinces except for Quebec, we identified the frequency of prescribing and cost of potentially inappropriate medications dispensed to provincial drug plan enrollees aged 65 years or more. Potentially inappropriate prescriptions were defined with the use of the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. Results: For the 6 provinces with relatively complete data coverage (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario and Prince Edward Island), 37% of older people filled 1 or more prescription meeting the Beers Criteria. A higher proportion of women (42%) than men (31%) filled potentially inappropriate prescriptions. The highest rates of prescribing of potentially inappropriate medications were among women aged 85 or more (47%). Benzodiazepines and other hypnotics were the leading contributors to the overall frequency of and sex differences in prescribing of potentially inappropriate drugs among older adults. We estimated that $75 per older Canadian, or $419 million in total, was spent on potentially inappropriate medications outside of hospital settings in 2013. Interpretation: Prescribing of potentially inappropriate medications for older adults is common and costly in Canada, especially for women. Multipronged and well-coordinated strategies to reduce the use and cost of potentially inappropriate drugs would likely generate significant health system savings while simultaneously generating major benefits to
Sharif, Si; Al-Shaqra, M; Hajjar, H; Shamout, A; Wess, L
To determine the pattern of drug prescription by consultants in a private hospital in Dubai, United Arab Emirates, 1190 prescriptions were collected from the hospital's pharmacy over 30 days. In total, 2659 drugs were prescribed. The mean number of drugs per encounter was 2.2. Only 4.4% of all drugs prescribed were generic. Polypharmacy was observed in only 7.5% of all encounters. Information about the prescribing physician and the patient was invariably deficient. Name of patient, age, and gender were absent in 2.9%, 9.7%, and 12% of prescriptions, respectively. In addition, none of the prescriptions mentioned address, diagnosis, or allergy of the patient. Name of physician, signature, speciality and license or registration number were omitted in 12.2%, 10.3%, 20.3%, and 54.9% of prescriptions. The most commonly prescribed therapeutic classes of drugs (and principal drug in each class) were as follows: 23.4% non-steroidal anti-inflammatory drugs (NSAIDs, Diclofenac sodium being 51.6%), 21.4% antibiotics (amoxicillin-clavulanate 13.5%), and 11.5% gastrointestinal drugs (GI, Hyoscine-N-butylbromide 28.1%). Other therapeutic classes included endocrine drugs (6.1%), vitamin supplements (5.9%), nasal decongestants (4%), antihistaminics (3.8%) and cardiovascular drugs (2.6%). Antibiotic injections accounted for 7.4% of all antibiotics prescribed, which was equivalent to 1.6% of all prescriptions. Other agents prescribed in small proportions of encounters collectively amounted to 21.3%. This study reveals the prescription trends, and indicates possible areas of improvement in prescription practice.
Robinson, M. S.; Anthony, T. R.; Littau, S. R.; Herckes, P.; Nelson, X.; Poplin, G. S.; Burgess, J. L.
Wildland firefighters are exposed to particulate matter and gases containing polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. Our objective was to evaluate the extent of firefighter exposure to particulate and PAHs during prescribed pile burns of mainly ponderosa pine slash and determine whether these exposures were correlated with changes in urinary 1-hydroxypyrene (1-HP), a PAH metabolite. Personal and area sampling for particulate and PAH exposures were conducted on the White Mountain Apache Tribe reservation, working with 21 Bureau of Indian Affairs/Fort Apache Agency wildland firefighters during the fall of 2006. Urine samples were collected pre- and post-exposure and pulmonary function was measured. Personal PAH exposures were detectable for only 3 of 16 PAHs analyzed: naphthalene, phenanthrene, and fluorene, all of which were identified only in vapor-phase samples. Condensed-phase PAHs were detected in PM2.5 area samples (20 of 21 PAHs analyzed were detected, all but naphthalene) at concentrations below 1 μg m−3. The total PAH/PM2.5 mass fractions were roughly a factor of two higher during smoldering (1.06 ± 0.15) than ignition (0.55 ± 0.04 μg mg−1). There were no significant changes in urinary 1-HP or pulmonary function following exposure to pile burning. In summary, PAH exposures were low in pile burns, and urinary testing for a PAH metabolite failed to show a significant difference between baseline and post-exposure measurements. PMID:18515848
Tichelaar, J; Schutte, T; Benemei, S; Böttiger, Y; Chamontin, B; Christiaens, T; Likic, R; Maˇiulaitis, R; Marandi, T; Monteiro, EC; Papaioannidou, P; Pers, YM; Pontes, C; Raskovic, A; Regenthal, R; Sanz, EJ; Tamba, BI; Wilson, K; de Vries, TP; Richir, MC; van Agtmael, MA
European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final‐year medical students across Europe. In a cross‐sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final‐year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final‐year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed. PMID:27648725
How antipsychotic drugs compare in schizophrenia, and especially in medication-refractory schizophrenia, is a subject of considerable interest. Two network meta-analyses and 1 direct comparison meta-analysis recently compared antipsychotics in schizophrenia patients with and without documented treatment resistance. One network meta-analysis of antipsychotic drugs in non-refractory patients found clear efficacy advantages for clozapine, amisulpride, olanzapine, and risperidone. One network meta-analysis of antipsychotic drugs in refractory patients found a clear efficacy advantage for olanzapine; surprisingly, in this meta-analysis, clozapine was superior to first-generation but not second-generation antipsychotics. One direct comparison meta-analysis found clozapine generally superior to first- and second-generation antipsychotics, with advantages more clearly apparent in studies that were 3 months in duration or less. Drug discontinuation and adverse effect data from these meta-analyses are presented, and issues arising from the results are briefly discussed. At the risk of oversimplification, it appears that clozapine retains its preeminence in medication-refractory schizophrenia and that clozapine and olanzapine are both associated with superior efficacy outcomes in non-refractory patients. Interestingly, haloperidol, generally considered a reference neuroleptic and a reference comparator drug, fared poorly in most comparisons.
Schuhmacher, Anna; Becker, Tim; Rujescu, Dan; Quednow, Boris B; Lennertz, Leonhard; Wagner, Michael; Benninghoff, Jens; Rietschel, Marcella; Häfner, Heinz; Franke, Petra; Wölwer, Wolfgang; Gaebel, Wolfgang; Maier, Wolfgang; Mössner, Rainald
Serotonergic transmission is considered relevant in the pathophysiology and the treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be associated with schizophrenia, studies focusing on TPH2 variants did not yield conclusive results for schizophrenia or the response to antipsychotic medication. We analyzed eleven TPH2 SNPs in two case-control samples consisting of 4453 individuals in total. Six SNPs were selected because of their potential functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115, and, rs4290270) and were supported by another 5 tagging SNPs selected based on HapMap LD information. In the discovery sample (1476 individuals), we observed a significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G-allele 0.82 [0.71-0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71-0.96]). Association was also observed with a common rs4570625-rs4565946 haplotype (OR G-C haplotype 1.20 [1.02-1.40]; p = 0.0046). Single-marker associations could not be replicated in the replication sample consisting of 2977 individuals, but there was a strong trend regarding the rs4570625-rs4565946 G-C haplotype (OR 1.10 [0.98-1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare rs4570625-rs4565946 T-T haplotype was associated with reduced processing speed (n = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia patients. TPH2 variants and the rs4570625-rs4565946 G-C haplotype did not influence the beneficial response to antipsychotic drugs (n = 210) after four weeks of treatment administering the Positive and Negative Syndrome Scale of Schizophrenia (PANSS). We also investigated the association of the SNPs to treatment response, but did not get significant results. In sum, our results argue for only a minor role of TPH2 in schizophrenia.
Choudhury, Dwijen Kumar; Bezbaruah, Babul Kumar
Objectives: The aim of this study is to evaluate the prescribing pattern of analgesics and analyze the rational use of analgesic in orthopedic in-patient department of tertiary care teaching hospital, Guwahati, Assam. Subjects and Methods: An observational and cross-sectional study was carried out for 1 month from April to May 2014. Collected data included age, sex, diagnosis and line of management during the study. The generic name and the average cost of treatment per patient were evaluated using Indian Drug Review, 2014. The prescribed drugs were assessed with respective National Model List of Essential Medicines (NLEM), 2011 and the rationality of prescriptions was determined using the World Health Organization indicators of drug utilization. The patients’ details were recorded in a predeigned data collection form and results were analyzed by descriptive statistics. Results: Out of 200 patients, 123 were male and 77 were female. The average number of analgesic per prescription was 1.46. In this study, 55.5% of patients had received single analgesic. Diclofenac was the most commonly prescribed analgesic (43.49%). During hospitalization, majority of the patients have received parenteral preparation. Gastroprotective agents and antimicrobials were frequently prescribed along with analgesics. Out of 292 analgesics prescribed, 183 (62.67%) were from the NLEM, India. Furthermore, 176 (57.19%) analgesics were prescribed by generic name. The average cost of treatment per patient was 2151.72 INR. Utilization of analgesic in terms of defined daily dose/100 bed-days was 104.01. Conclusion: The percentages of analgesics prescribing from NLEM and the use of analgesic by generic name were found satisfactory. Regular educational interventions to improve prescribing practices among physicians at different levels may further promote rational prescribing. PMID:27756947
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Need to follow prescribed treatment. 220.115 Section 220.115 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT DETERMINING DISABILITY Medical Considerations § 220.115 Need to follow prescribed treatment....
... Electronic Data Interchange Technical Report Type 3—Health Care Eligibility Benefit Inquiry and Response (270... 42 Public Health 3 2012-10-01 2012-10-01 false Standards for electronic prescribing. 423.160... and Quality Improvement Requirements § 423.160 Standards for electronic prescribing. (a) General...
... by § 250.48. (e) Matters as to which no form is prescribed. As to any proposed transactions, and any... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Prescribed forms and... (CONTINUED) GENERAL RULES AND REGULATIONS, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 Forms, Procedure...
... use of electronic prescribing technology by eligible professionals. Eligible professional means any of the following healthcare professionals who have prescribing authority: (i) A physician. (ii) A...)(1)(A) of the Act with respect to a certified electronic health record technology (as defined...
... 42 Public Health 3 2011-10-01 2011-10-01 false Standards for electronic prescribing. 423.160... Improvement Requirements § 423.160 Standards for electronic prescribing. (a) General rules. (1) Part D sponsors must establish and maintain an electronic prescription drug program that complies with...
... benefits, we will stop paying you benefits. (c) Acceptable reasons for failure to follow prescribed... failure to follow prescribed treatment. The following are examples of a good reason for not following... recommended for the same impairment. (4) The treatment because of its enormity (e.g. open heart...
... consolidated payment to the TIN holder of record. (ii) Applicable electronic prescribing percent. The... paragraph (c)(3) of this section), an individual eligible professional, as identified by a unique TIN/NPI... professional will receive only one electronic prescribing incentive payment per TIN/NPI combination for...
Alzaabi, Mohammed A.; Alghafri, Fatma
Introduction Inappropriate use of antifungal agents is implicated in the global burden of antifungal resistance, adverse outcomes like persistent infections, unnecessary exposure and increased cost. Data collection from time to time is to be done in order to have a check on the resistance/sensitivity pattern of the commonly prescribed antifungal drugs. Aim To describe the pattern of antifungal drug prescription and administration to patients attending a university hospital in Oman. Materials and Methods This was a descriptive, retrospective cross-sectional study conducted at Sultan Qaboos University Hospital (SQUH), a university hospital in Oman that covered the electronic patient’s data for a period of one year (January 2013 to December 2013). The study included inpatients and outpatients of all ages and both genders attending SQUH and receiving antifungal medications at the study period. Frequencies and percentages were reported for categorical variables, while the mean and standard deviation were used to summarize the data for continuous variables. Results A total of 1353 antifungal drug prescriptions were prescribed for 244 patients. More than half of all antifungal drug prescriptions were prescribed by haematology, infectious disease and family medicine departments. The majority of patients to whom these drugs were prescribed were diagnosed to have infectious diseases followed by prophylactic use in leukaemias and immunocompromised conditions. Fluconazole was the most commonly prescribed antifungal drug (n=715, 52.8%) followed by nystatin and voriconazole (n=233; 17.2% and n=152; 11.2%, respectively). Conclusion This study will help in understanding antifungal prescription practices and help in directing future studies and also in developing local policies for appropriate use of antifungal drugs. PMID:28208876
Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa
Objective To offer preliminary guidance on prescribing smoked cannabis for chronic pain before the release of formal guidelines. Quality of evidence We reviewed the literature on the analgesic effectiveness of smoked cannabis and the harms of medical and recreational cannabis use. We developed recommendations on indications, contraindications, precautions, and dosing of smoked cannabis, and categorized the recommendations based on levels of evidence. Evidence is mostly level II (well conducted observational studies) and III (expert opinion). Main message Smoked cannabis might be indicated for patients with severe neuropathic pain conditions who have not responded to adequate trials of pharmaceutical cannabinoids and standard analgesics (level II evidence). Smoked cannabis is contraindicated in patients who are 25 years of age or younger (level II evidence); who have a current, past, or strong family history of psychosis (level II evidence); who have a current or past cannabis use disorder (level III evidence); who have a current substance use disorder (level III evidence); who have cardiovascular or respiratory disease (level III evidence); or who are pregnant or planning to become pregnant (level II evidence). It should be used with caution in patients who smoke tobacco (level II evidence), who are at increased risk of cardiovascular disease (level III evidence), who have anxiety or mood disorders (level II evidence), or who are taking higher doses of opioids or benzodiazepines (level III evidence). Cannabis users should be advised not to drive for at least 3 to 4 hours after smoking, for at least 6 hours after oral ingestion, and for at least 8 hours if they experience a subjective “high” (level II evidence). The maximum recommended dose is 1 inhalation 4 times per day (approximately 400 mg per day) of dried cannabis containing 9% delta-9-tetrahydrocannabinol (level III evidence). Physicians should avoid referring patients to “cannabinoid” clinics (level
Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings
To determine the medication prescribing patterns in hospitalized patients with chronic kidney disease (CKD) in a Malaysian hospital, we prospectively studied a cohort of 600 patients in two phases with 300 patients in each phase. The first phase was carried out from the beginning of February to the end of May 2007, and the second phase was from the beginning of March to the end of June 2008. Patients with CKD who had an estimated creatinine clearance ≤ 50 mL/min and were older than 18 years were included. A data collection form was used to collect data from the patients' medical records and chart review. All systemic medications prescribed during hospitalization were included. The patients were prescribed 5795 medications. During the first phase, the patients were prescribed 2814 medication orders of 176 different medications. The prescriptions were 2981 of 158 medications during the second phase. The mean number of medications in the first and second phases was 9.38 ± 3.63 and 9.94 ± 3.78 respectively (P-value = 0.066). The top five used medications were calcium carbonate, folic acid/vitamin B complex, metoprolol, lovastatin, and ferrous sulfate. The most commonly used medication classes were mineral supplements, vitamins, antianemic preparations, antibacterials, and beta-blocking agents. This study provides an overview of prescription practice in a cohort of hospitalized CKD patients and indicates possible areas of improvement in prescription practice.
Nurmi, E L; Spilman, S L; Whelan, F; Scahill, L L; Aman, M G; McDougle, C J; Arnold, L E; Handen, B; Johnson, C; Sukhodolsky, D G; Posey, D J; Lecavalier, L; Stigler, K A; Ritz, L; Tierney, E; Vitiello, B; McCracken, J T
Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4–17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10−6), CNR1 (P=9.6 × 10−5) and the leptin (LEP) promoter (P=1.4 × 10−4) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10−9) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event. PMID:23799528
Food and Drug Administration–approved information and public advertisements belie neurodegenerative risks for second-generation antipsychotics in affective illness. Package inserts label tardive syndromes “potentially reversible” while uniformly omitting patient counseling for long-term neurodegenerative side effects. I found that only 2 of 78 outpatients exposed to second-generation antipsychotics reported awareness of tardive syndromes. Updated literature challenges safety advantages of atypical versus typical antipsychotics. Physician and patient information regarding tardive syndromes from second-generation antipsychotics approved for affective illness is inadequate. PMID:25521884
Mandrioli, Roberto; Protti, Michele; Mercolini, Laura
Medicinal chemistry is continually developing and testing new drugs and drug candidates to satisfactorily address the needs of patients suffering from schizophrenia. In the last few years, some significant additions have been made to the list of widely available atypical antipsychotics. In particular, iloperidone, asenapine and lurasidone have been approved by the USA's Food and Drug Administration in 2009-10. In this paper, the most notable metabolic characteristics of these new drugs are addressed, with particular attention to their potential for pharmacokinetic interactions, and to the respective advantages and disadvantages in this regard. Moreover, current perspectives on the therapeutic drug monitoring (TDM) of the considered drugs are discussed. Since TDM is most valuable when it allows the personalisation and optimisation of therapeutic practices, it is even more interesting in the case of novel drugs, such as those discussed here, whose real impact in terms of side and toxic effects on very large populations is still unknown. Some analytical notes, related to TDM application, are included for each drug.
Malla, Ashok; Tibbo, Phil; Chue, Pierre; Levy, Emmanuelle; Manchanda, Rahul; Teehan, Michael; Williams, Richard; Iyer, Srividya; Roy, Marc-André
A major source of limitation to the real effectiveness of antipsychotics is the high rate of patient nonadherence or, more frequently, partial adherence. Using long-acting injectable (LAI) formulations is likely to reduce the impact of such adherence problems. Conversely, the use of LAIs in Canada remains low relative to many other jurisdictions. Based on effectiveness data from randomized control trials and other, less rigorous, studies, as well as our 2 qualitative studies exploring numerous issues around the use of LAIs, including their low use, we put forward 10 different recommendations for consideration by clinicians. These are also based on the experience of many clinicians and clinician scientists. These recommendations address mostly clinical challenges associated with the use of LAIs. Their application in clinical settings is illustrated in our report through several case examples highlighting the large variation across patients and different phases of illness. It is recommended that LAIs should be considered as a treatment option for psychotic disorders across all phases, including the first 2 to 5 critical years.
Ward, Stephen; Wasson, Gemma
One of the challenges for Foundation Year 1 junior doctors is to apply the theoretical pharmacology from their undergraduate years into practical prescribing. The EQUIP study in 2009 investigated the causes of prescribing errors by junior doctors. Respondents in the study reported deficiencies in their education for prescribing skills and error prevention. The study suggested more could be done during undergraduate education to link theory with practice. This article describes an initiative from a hospital clinical pharmacy team to address this gap in contextual prescribing skills. Final year medical students (FY0s) were allocated to the Belfast Trust for an 11 week placement. The Clinical Pharmacy team developed a 3 h FY0 workshop focusing on practical prescribing scenarios identified as high risk by local medicines safety teams. The workshops included simulated case studies requiring the FY0 student to discuss medicine use with patients, prescribe admission drug charts and use local guidelines to safely prescribe high risk medicines. Each student was assessed using direct observation of procedural skills (DOPS). Feedback was overwhelmingly positive. Students appreciated the practical elements of the workshop. Initially there was an over-reliance on written medication history without verbally engaging the patient. Following pharmacist feedback before the DOPS students demonstrated a clear improvement in patient communication. Feedback from the FY0 students also identified additional learning needs that formed the basis of further teaching.
Bourne, Richard S; Baqir, Wasim; Onatade, Raliat
In recent years a number of countries have extended prescribing rights to pharmacists in a variety of formats. The latter includes independent prescribing, which is a developing area of practice for pharmacists in secondary care. Potential opportunities presented by wide scale implementation of pharmacist prescribing in secondary care include improved prescribing safety, more efficient pharmacist medication reviews, increased scope of practice with greater pharmacist integration into acute patient care pathways and enhanced profess