An update on medication management of women with schizophrenia in pregnancy

Introduction: Women with schizophrenia and their babies are at high risk of adverse outcomes in pregnancy and childbirth. A better understanding of the specific risks conferred by the illness itself and by the treatment provided will help guide more effective care of these women.

Areas covered: Herein, the authors review genetic, demographic, socioeconomic, nutritional and lifestyle risks associated with schizophrenia in pregnancy. They also cover specific risks associated with typical antipsychotic medications, specific risks associated with atypical antipsychotic medications, risks associated with polypharmacy and risks of developmental delay in children exposed to antipsychotic medications in utero.

Expert opinion: Our understanding of the risks that women with schizophrenia face in pregnancy from their illness and from the treatment they receive continues to evolve. As our ability to analyze data progresses, the risks conferred by antipsychotic medication treatment appear to lessen in clinical and statistical significance, whilst the true risks to these women and their babies from their experience of disadvantage continue to set them aside from the general population. Reducing polypharmacy and providing comprehensive and supportive care can minimize harm to women with schizophrenia and their babies.     

Evaluation of WO2014121383 A1: a process for preparation of rufinamide and intermediates

Introduction: There is great potential in the synthetic development of rufinamide to treat childhood-onset epilepsy known as Lennox–Gastaut syndrome (LGS).

Areas covered: 1,4-disubstituted triazole ring formed by 1,3-dipolar cycloaddition reaction is an important structural motif widely used to construct diverse chemotypes in chemical, biological, and material fields. 1,2,3-triazole ring containing rufinamide, an antiepileptic drug developed by Novartis, is useful in combination with other antiepileptic medicaments for the treatment of childhood-onset epilepsy known as LGS. There are numerous synthetic methods used to construct the rufinamide through 1,3-dipolar cycloaddition. The application claims processes for the preparation of rufinamide and their intermediates. The synthetic strategy covered for the synthesis of rufinamide using activated acetylenic esters. The activation is done using N-hydroxy succinimide, N-hydroxyphthalimide, 1-hydroxy benzotriazole, and 4-nitro phenol.

Expert opinion: The manufacturing route appears to follow the regioselective Cu catalyzed cycloaddtion of 2,6-difluro benzyl azide with or without isolated activated acetylenic esters in three steps that provide a good lead for new synthetic strategy for the rufinamide synthesis.     

The burden of at-home preparation of lyophilized parenteral medications: an analysis of contributing factors and implications for chronic disease patients and caregivers

Background: In the acute care setting, parenteral medication errors are well-studied. However, there is comparatively little research on how these issues translate to patient- or caregiver-prepared medications in the home, particularly with reconstituted medications.

Methods: This was an ethnographic study designed to identify issues associated with four reconstitution use scenarios. Preparation burden was determined by measuring the time and manipulations required to prepare reconstituted medications across three preparation phases (assembly, reconstitution, and transfer). Deviations from product instructions for use, sterility breaches, self-reported preparation complications, and supply storage conditions were also analyzed.

Results: A total of 14 participants completed the study. Overall, preparation burden was markedly higher when purpose-built reconstitution devices were not available. The majority of participants reported experiencing at least one complication associated with their medication preparation process; the reconstitution phase was the most significant source of both instructions for use deviations and breaches in sterility. Participants reported that the volume and variety of medication preparation supplies were a significant source of burden.

Conclusions: At-home preparation of reconstituted medications poses several challenges for patients and caregivers. As parenteral medications continue to shift towards self-administration, manufacturers should carefully consider the usability of such products and employ purpose-built reconstitution devices whenever possible.     

An evaluation of zonisamide,including its long-term efficacy,for the treatment of focal epilepsy

Introduction: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention.

Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information.

Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.     

A 30-year follow-up of substance misusers in Sweden – differences in predictors of mortality between women and men

Background: Differing results on gender specific factors related to mortality risks among substance misusers highlights the need for further research. The present article is based on a 30-year follow-up study on substance misusers treated in residential care for drug problems in Sweden in 1982-1983 aiming to identify and compare gender differences in predictors of mortality.

Method: Original data consists of personal interviews with 1163 substance misusers treated in inpatient units in Sweden during 1982-1983. The outcome variable is death retrieved from the National Cause of Death Register held by the National Board of Health and Welfare. Gender differences and similarities regarding predictors of mortality was estimated in univariate and multivariate models, using Cox proportional hazards models.

Results: School failure, imprisonment and being a parent without custody of the child seem to constitute risk factors for mortality among women, but not among men. A social network of friends seemed to be more important for men. Treatment-dropout was a significant risk factor for premature death among men, but not among women. Both gender reporting alcohol as their self-reported most dominant substance misuse showed higher mortality risks compared with those with stimulants as dominant substance misuse.

Conclusions: Imprisonment was highly predictive of mortality for the women, suggesting that this group is important to pay particular attention to. Suggested differences in the importance of social factors need to be investigated more thoroughly. The substantial hazard revealed for women with polydrug misuse including alcohol calls for attention to this in treatment for substance misuse.     

Potentially inappropriate concomitant medicine use with the selective COX-2 inhibitor celecoxib: Analysis and comparison of spontaneous adverse event reports from Australia,Canada and the USA.

Background: To perform an international comparison and analysis of celecoxib spontaneous adverse event reports (AERs) from Canada, Australia and the United States, focusing on gastrointestinal, renal and cardiovascular events. This study also examined concomitant medicines use which may have potentiated the risk of the reported adverse events.

Research, design and methods: Three databases were searched for spontaneous AERs associated with celecoxib, submitted within the past 10 years: Australian Therapeutic Goods Administration Database of Adverse Event Notifications; Canada Vigilance Adverse Reaction Online Database; and the United States Food and Drug Administration Adverse Event Reporting System Database. Analysis of the AERs focussed on the identification of gastrointestinal, cardiovascular and renal adverse events and concomitant medications suspected of potentiating adverse event risks.

Results: A total of 24,232 celecoxib AERs were identified. Gastrointestinal disorders were the most frequently reported adverse events at the system organ class (SOC) level in the AERs. A large number of AERs documented the use of potentially inappropriate concomitant medicines which may have increased the risk of the reported adverse events.

Conclusions: The large number of reports that involved a concomitant medicine that was in contravention with prescribing guidelines indicates an increased need for efforts to support the safe prescribing of celecoxib.     

Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Assessment of adherence to medication in patients after myocardial infarction treated with percutaneous coronary intervention. Is there a place for newself-reported questionnaires?

Introduction: Non-adherence to medication regimen after myocardial infarction (MI) leads to increased morbidity and mortality and generates additional cost to the healthcare system.

Objectives: The aim of this systematic review was to critically discuss assessment methods of adherence to medication in patients after myocardial infarction treated with percutaneous coronary intervention and the possible application of a new self-reported questionnaire.

Methods: A systematic investigation of all published literature was conducted to minimize the risk of bias. A database search (PubMed, CENTRAL and Google Scholar databases) from January 1998 through December 2017.

Results: Adequate assessment of patient adherence to treatment is necessary to understand the potential for adverse outcomes. Methods developed for adherence evaluation are classified as subjective and objective or as direct and indirect. Direct, objective measures reflect pharmacokinetics and include measurement of the drug or its metabolite concentration, evaluation of the presence of biological markers given with the drug and direct observation of patients’ medication-taking behavior. Several indirect, objective methods are based on evaluation of the availability of prescribed medications assuming that medication is taken exactly as prescribed. Assessment of the effectiveness of treatment, both at the pharmacodynamic and clinical level, indirectly but objectively reflects adherence to treatment. Subjective methods, including patient-kept diaries, patient interviews and self-reported questionnaires, due to their simplicity, real-time feedback and low cost, are often used for adherence evaluation in clinical practice.

Conclusions: In spite of the availability, convenience and variety of methods, measuring adherence still remains a real challenge. Using a well designed questionnaire provides an opportunity to identify patients at increased risk of non-adherence and the obstacles impeding implementation of the treatment plan, allowing implementation of tailored interventions in order to improve patient medication-taking behavior.     

Gender,subclinical organ damage and cardiovascular risk stratification in hypertensive patients

Background: The aims of the study were to assess subclinical organ damage in men and women with hypertension and its subsequent effect on cardiovascular risk, and use of new statistical methods for more precise estimation of cardiovascular risk using vascular cardiovascular risk factors: ankle–brachial index (ABI), intima–media thickness (IMT) and pulse wave velocity (PWV).

Methods: We studied 200 patients: 100 hypertensive and 100 normotensive. The parameters we evaluated included: patient age, ABI, IMT, PWV, serum uric acid and serum C-reactive protein (CRP). In addition, the cardiovascular risk according to the SCORE and Framingham scales was assessed.

Results: In the hypertensive group, there were significant correlations between ABI and the Framingham scale in both sexes. In hypertensive women, there were also significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.

In normotensive women, there were significant correlations between ABI and the SCORE scale risk, and between ABI and the Framingham scale risk. In normotensive men, there were significant correlations between PWV and the SCORE scale risk, and between PWV and the Framingham scale risk. Lastly, in the group of normotensive men, there were significant correlations between IMT and the SCORE scale risk, and IMT and the Framingham scale risk.

The possibility of correctly classifying a patient into the high-risk category by a logistic regression model using synchronous ABI, IMT and PWV was high – 74% for the risk according to the SCORE scale (66% in men, 88% in women), and 98% for the Framingham scale.

Conclusions: The addition of recognized subclinical target organ damage tests to the estimation of cardiovascular risk can significantly strengthen the prevention of cardiovascular disease.

Cardiovascular risk estimation follow-up with ABI, PWV and IMT increased the probability of correctly classifying people, especially women, into an at least high-risk category according to the SCORE scale, which has valuable therapeutic implications.     

Routine care interventions with the parents of adult drug and alcohol users

Introduction and aims: To explore routine care interventions which enable parents to support the therapeutic effort of their adult child in drug and alcohol treatment.

Design and methods: Inductive content analysis was used to analyze the experiences of 31 Greek addiction professionals who participated in focus groups.

Findings: Professionals adopted various interventions which included (a) respond to parents quest for help, (b) involvement of the distant parent in treatment, (c) boundary setting, (d) facilitation of parent-child communication, and (e) support of parental changes. These interventions were perceived as necessary, both for motivating and sustaining the client’s change, and for alleviating the parents’ chronic grief and distress over their child’s addiction.

Conclusion: Overall, addiction professionals perceived low intensity interventions, information giving, and non- judgmental informal interactions as catalysts for the parents involvement in addiction treatment.     

An evaluation of peripapillar choroidal thickness in patients receiving systemic isotretinoin treatment

Purpose: Oral isotretinoin (13-cis retinoic acid, 13-cis RA) was approved for severe acne treatment by the FDA in 1982. The ocular side effects associated with oral isotretinoin use are mostly dose-dependent. Numerous ocular pathologies affect peripapillary choroidal layer primarily or indirectly.

Objective: Evaluation of the peripapillary choroidal layer in the patients receiving oral isotretinoin therapy may aid in explaining the pathophysiology of ocular side effects.

Methods: In this study, peripapillary choroidal thickness was assessed in the patients receiving oral isotretinoin treatment via optical coherent tomography technique.

Results: Significant difference was found in the superotemporal and temporal areas.

Conclusion: Oral isotretinoin treatment may affect the thickness of the peripapillary choroidal layer.     

The quality of spontaneous adverse drug reaction reports from the pharmacovigilance centre in western China

Background: High-quality adverse drug reaction (ADR) reports are essential for conducting drug safety monitoring in pharmacovigilance. The study aim was to assess the current quality of ADR reports in western China, and to identify problems with ADR report quality.

Research design and methods: A sample of 1139 reports received by the Shaanxi ADR Monitoring Center from January 2015 to December 2017 was selected. ADR report quality was evaluated using an ADR report quality evaluation system.

Results: None of the reports were rated as excellent and 1.40% (n = 16) as good. Report quality was better for new and serious reports than for general reports. Medical institutions generated higher quality reports than pharmaceutical manufacturers. Nurses generated higher quality reports than doctors, pharmacists, and other professionals. Reporters of different occupations showed significant differences in the quality of the indicators Reporting time limit, Intervention ADR time, ADR termination time, ADR intervention measures, Original disease, and Cause of medication (P = 0.000).

Conclusions: The ADR data quality was poor in western China, and of lower quality than reported data from previous research in other regions. Improvements in the quality and availability of ADR reports are urgently needed.     

Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

Optimisation of the microencapsulation of lavender oil by spray drying

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions.

Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.

Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.

Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).

Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.     

Study description and baseline characteristics of the population enrolled in a multinational,observational study of teriparatide in postmenopausal women with osteoporosis: the Asia and Latin America Fracture Observational Study (ALAFOS)

Objective: To describe the study design and baseline patient characteristics of the Asia and Latin America Fracture Observational Study (ALAFOS) to better understand the profile of patients receiving teriparatide during the course of routine clinical practice in Asia, Latin America, the Middle East and Russia.

Methods: Prospective, observational, non-interventional study in postmenopausal women with osteoporosis who are prescribed teriparatide for up to 24?months, according to local medical standards, with a 12?month post-treatment follow-up.

Measures: Demographics, risk factors for osteoporosis and fractures, history of fracture, prior osteoporosis medications, comorbidities, physical function, back pain and quality of life (QoL).

Results: In total 3031 postmenopausal women (mean age 72.5?years) recruited at 152 sites in 20 countries were analyzed; 62.9% had a history of fragility fracture after age 40 (33.0% of patients with spinal, 14.2% with hip fractures). The mean (SD) bone mineral density T-scores at baseline were ?3.06 (1.40) and ?2.60 (1.05) at the lumbar spine and femoral neck, respectively. At entry, 43.7% of patients were naïve to prior osteoporosis treatments; 40.5% of patients reported ≥1 fall in the past year. The median (Q1; Q3) EuroQoL Visual Analog Scale (EQ-VAS) for perceived overall health status was 60 (50; 80). The mean (SD) worst back pain Numeric Rating Scale in the last 24?hours was 4.6 (3.3).

Conclusions: Our data indicates that patients who were prescribed teriparatide in the ALAFOS participant countries had severe osteoporosis, high prevalence of fractures, disabling back pain and poor QoL. The frequency of patients receiving prior osteoporosis medications was lower than in previous observational studies conducted in other locations.     

Treating obesity in patients with cardiovascular disease: the pharmacotherapeutic options

Introduction: Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others.

Areas covered: Herein, the authors review the most commonly used FDA approved medications for the treatment of obesity, describing their mechanism of action, and the efficacy and safety of the medications as seen in recent studies, particularly in patients with CVD.

Expert opinion: In the population of patients with obesity and CVD, the medications orlistat, lorcaserin and liraglutide are considered the most appropriate options for their treatment, in terms of safety. Sympathomimetic medications, such as phentermine, should be avoided in this group. The recent CAMELLIA-TIMI 61 trial supports the safety of lorcaserin in patients with CVD. Until there are more studies, it is reasonable to extrapolate the findings of the LEADER trial, which found improved CV outcomes in subjects with type 2 diabetes taking liraglutide, to the population of nondiabetic patients being treated for obesity. Further cardiovascular outcomes trials (CVOT) are needed to assess the safety of other pharmacotherapeutic options for weight loss.     

Current and emerging drug therapies for the treatment of depression in adults with epilepsy

Introduction: Depression is the most frequent psychiatric comorbidity among people with epilepsy. It can impact on quality of life and increases the risk of morbidity and premature mortality.

Areas covered: The authors review the available data on current and emerging drug treatments for depression in epilepsy. Sources have been identified through Medline/PubMed searches while ongoing clinical trials have been identified through a ClinicalTrials.gov search.

Expert opinion: SSRIs are the drug class with the largest amount of data. Though promising, the level of evidence provided by these studies is still low as the majority have relevant methodological limitations. Antiepileptic drugs under development have the unique opportunity to be of multi-use in the treatment of epilepsy and depression. The serotoninergic system has already been identified as a potential area of interest, but new targets are still needed in epilepsy and depression. For this reason, it is important that basic scientists working on these two conditions develop collaborative projects and integrate findings.     

Development of a list of high-risk perioperative medications for the elderly: a Delphi method

Objectives: There is a lack of direct evidence for the management of perioperative medications in elderly patients. Therefore, the authors aimed to develop a list of high-risk medications for the elderly population in China to provide indicators for clinicians to identify medication-related factors contributing to potential adverse events during the perioperative period.

Methods: The initial list of high-risk perioperative medications was developed by studying all the publications that described specific high-risk medications and their risk profiles in the elderly. Delphi consultations were performed to form a consensus among the group of experts and the list was finalized.

Results: The expert panel consisted of 36 experts from 29 tertiary hospitals and 18 provinces or municipalities. The consensus was reached after two Delphi rounds. Finally, a total of 86 medications of 13 medication classes and 120 screening items were included in the final list, along with perioperative risk profiles and risk aversion recommendations for each drug.

Conclusion: This is the first study to establish a high-risk perioperative medication list in China, which can be used as a reference for intervention and evaluation of perioperative medications for the elderly population.     

Safety of drugs used for the treatment of Crohn’s disease

Introduction: Medications in treating Crohn’s disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn’s disease in adult patients.

Areas covered: The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on ‘trial’ and ‘real-world’ data for the biologic agents. Safety in pregnancy and the elderly are also presented.

Expert opinion: Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated; however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.     

Research on medication use in the neonatal intensive care unit

Introduction: Research on medication use aims at assessing how much of current pharmacotherapy is rational. In neonates, this is hampered by extensive off-label drug use and limited knowledge.

Areas covered: We report on medication use research and have conducted a systematic review of observational studies on medication use to provide an updated overview on characteristics, objectives, methods, and patterns in hospitalized neonates. Moreover, a review on aspects of medication use for opioids, anti-epileptics, gastric acid-related disorders and respiratory stimulants with emphasis on trends and impact of interventions is presented, illustrating how research on medication use can contribute to improved neonatal pharmacotherapy and more focused research. Medication use reports describe patterns and provide signals on irrational use, benchmarking, or can guide research priorities. Moreover, this may generate information on how neonatal health topics and their pharmacotherapy are handled over time or across regions.

Expert opinion: Research on medicine utilization is relevant, since it will inform us on aspects like trends, variability, or about the impact and pattern of implementation of guidelines in neonates. Further progress necessitates to merge datasets on medication use with clinical characteristics, and perinatal drug use remains an area in need of additional research.