Attitudes toward psychiatric drug treatment: the experience of being treated

Background

Effectiveness and tolerability of psychiatric medications are not only determined by the drug’s pharmacological profile but through the interaction of different factors, including patients’ attitudes toward their prescribed medications. Increased knowledge about those attitudes may help prescribers to improve patient concordance and thereby the effectiveness of the pharmacological therapy.

Objective

The goal of this study was to assess stable psychiatric outpatients’ attitudes toward psychiatric drug treatment and to what extent patients and public opinions on this subject diverge as a consequence of being on this type of medication.

Methods

Two anonymous self-reported questionnaires [Drug Attitude Inventory (DAI)-10 and an abridge version of Beliefs about Medicines Questionnaire (BMQ)] were administered to 270 stable psychiatric outpatients under treatment and 292 citizens naïve to psychotropic medication.

Results

Psychiatric patients showed a more positive attitude toward medication (DAI score 3.6 vs. ?0.7; range ?10 to +10; negative to positive). Up to 77% of patients showed positive scores compared with only 36% in the general population. Multiple regression analysis showed that none of the variables in the analysis have a predictive value with regard to the attitude toward psychiatric drugs used.

Conclusion

The continuous use of psychotropic medication shapes the opinion of the users toward a more beneficial perception of medications, but the opinion on the general population, where stigmatizing attitudes are born, is more negative toward them. For psychiatrists and their patients, trying to achieve a better understanding of each other’s expectations and reaching concordance is mandatory.

     

Healthcare providers’ experiences with adverse drug reactions and adherence challenges in antiretroviral therapy of HIV patients in the Eastern Cape Province, South Africa

Purpose

To gain insight into the experiences and handling of adverse drug reactions (ADRs) by the staffs of public primary healthcare (PHC) clinics in Eastern Cape Province, South Africa, as well as their perceptions of related adherence challenges in the treatment and follow-up of human immunodeficiency virus (HIV)-positive patients.

Methods

Healthcare providers working at the PHC level in the public sector in the study area were approached and asked to participate in focus group discussions (FGDs). Seven FGDs were conducted with 32 healthcare providers (9 nurses, 23 auxiliary staff). Questions introduced by the moderator of each FGD were freely discussed by the participants. Discussions were audio-recorded and subjected to thematic content analysis.

Results

Several challenges in the treatment and follow-up of patients on ART were identified. These include: (1) lack of training of healthcare providers in PHC clinics to confidently identify, manage and treat the ADRs HIV-positive patients receiving ART; (2) patients’ difficulty in communicating information on ADRS; (3) insufficient pharmacovigilance; (4) role of poverty.

Conclusion

Both nurses and auxiliary staff expressed lack of knowledge and confidence regarding ADRs in HIV patients and management of this. More emphasis is warranted on training the healthcare providers to identify ADRs and provide adequate advice for continued treatment of patients experiencing potential drug related problems.     

The role of excipients in the control of dehydroepiandrosterone inclusion complex delivery

Aim

The aim of this study was to develop systems containing dehydroepiandrosterone (DHEA), in the form of an inclusion complex with α-cyclodestrin (c-DHEA), which are able to change the release profile of the hormone according to time and excipient composition.

Method

Twenty-five formulations were prepared containing DHEA (prasterone) in the chemical form of an inclusion complex with α-cyclodextrin (57.3% w/w). The drug was mixed with three different excipient systems: the first ‘fast’ one was a mixture of two disintegrants (microcrystalline cellulose and sodium carboxymethyl starch at prefixed 4.15 weight ratio); the second ‘gelling’ excipient contained two gel-forming agents (high viscosity hydroxypropyl methylcellulose and cross-linked polyvinyl pyrrolidone) at three weight ratios: 0.31, 1.00, and 2.45; and the third type of ‘binary’ mixture was prepared by combining ‘fast’ and ‘gelling’ systems at three weight ratios: 1:2, 1:1, and 2:1. Tablets were prepared by direct compression or after wet granulation of these formulations.

Results

’Fast’ tablets induced a rapid release of the drug while ‘gelling’ tablets were found to modify the release, according to composition. A profile, characterized by an initial phase of rapid drug release, followed by a period of slower release is achieved with series 1:1 tablets. Series 1:2 tablets provide linear release of the drug; while an undifferentiated profile was found for series 2:1 tablets.

Conclusion

Different release mechanisms and the control of drug release were obtained by using DHEA in its inclusion complex and varying the weight ratios of the excipients.     

Development of a Bionic System for the Simultaneous Prediction of the Release/Absorption Characteristics of Enteric-Coated Formulations

Purpose

To develop a new bionic system from an existing drug dissolution/absorption simulating system (DDASS) to simultaneously predict the release and absorption of enteric-coated formulations.

Methods

In accordance with the pH-dependent characteristics of enteric-coated formulations, the modified DDASS was designed to effectively imitate the pH change process of the formulations' transfer from stomach to intestine in vivo. Omeprazole enteric-coated tablets were chosen as the model drug to verify the rationality and feasibility of the modified DDASS. The correlations between USP I system release and beagle dog absorption, as well as between modified DDASS elution/permeation and beagle dog absorption, were investigated by linear and nonlinear regression analyses, respectively.

Results

In vitro-in vivo correlation between the modified DDASS elution/permeation method and beagle dog absorption was higher than between the USP I system release and beagle dog absorption in both analytical methods. The ratio of first-order permeation rate constant to first-order release rate constant was consistent with that from modified DDASS.

Conclusions

The modified DDASS provided more information than the USP I system did in the evaluation of enteric-coated formulations. The proposed bionic system model could serve as a new method for improving drug effectiveness.     

Electrospun Formulations Containing Crystalline Active Pharmaceutical Ingredients

Purpose

To investigate the use of electrospinning for forming solid dispersions containing crystalline active pharmaceutical ingredients (API) and understand the relevant properties of the resulting materials.

Method

Free surface electrospinning was used to prepare nanofiber mats of poly(vinyl pyrrolidone) (PVP) and crystalline albendazole (ABZ) or famotidine (FAM) from a suspension of the drug crystals in a polymer solution. SEM and DSC were used to characterize the dispersion, XRD was used to determine the crystalline polymorph, and dissolution studies were performed to determine the influence of the preparation method on the dissolution rate.

Results

The electrospun fibers contained 31 wt% ABZ and 26 wt% FAM for the 1:2 ABZ:PVP and 1:2 FAM:PVP formulations, respectively, and both APIs retained their crystalline polymorphs throughout processing. The crystals had an average size of about 10 μm and were well-dispersed throughout the fibers, resulting in a higher dissolution rate for electrospun tablets than for powder tablets.

Conclusions

Previously used to produce amorphous formulations, electrospinning has now been demonstrated to be a viable option for producing fibers containing crystalline API. Due to the dispersion of the crystals in the polymer, tablets made from the fiber mats may also exhibit improved dissolution properties over traditional powder compression.     

Functionalized Calcium Carbonate as a Novel Pharmaceutical Excipient for the Preparation of Orally Dispersible Tablets

Purpose

To overcome the limitation of insufficient hardness during the production of rapidly disintegrating orally dispersible tablets (ODTs). Furthermore, we investigated the properties and usefulness of functionalized calcium carbonate (FCC) as a new pharmaceutical excipient for the production of ODTs.

Methods

A highly sensitive tensiometer-based method was developed to measure kinetics of weight loss during tablet disintegration. With this method we were able to determine the residence time of tablets placed on a basket immersed into a test medium. The shapes of tensiometer plots allowed us to categorize substances into four different types of disintegration.

Results

At the same volume and hardness, the tablet formulations with FCC showed a significantly higher porosity (over 60%) than all other formulations. Residence time depended mainly on the tablet composition rather than on porosity. When combined with disintegrants, FCC formulations exhibited favorable disintegration properties, comparable to those of the marketed drug risperidone oro (disintegration time ca. 10 s).

Conclusions

Oral dosage forms - based on the new pharmaceutical excipient FCC - can be designed to have a short disintegration time combined with good mechanical strength. Due to these properties, FCC can be used for the preparation of ODTs.     

Clinical pharmacokinetics of once-daily molsidomine

Background

Molsidomine is a direct nitric oxide donor routinely used in the oral treatment of stable angina pectoris. It was initially available as 4mg immediate-release tablets to be taken three to four times a day. New galenic formulations have been developed: prolonged-release molsidomine 8mg to be administered twice daily and, more recently, prolonged-release molsidomine 16mg to be taken once daily, the latter being based on the patented and US FDA-approved Geomatrix® technology.

Objectives

This study has four objectives: (i) to compare and differentiate the pharmacokinetics of the different molsidomine formulations after single- and repeated-dose administrations; (ii) to put the new formulations in perspective with the literature and the critical minimal efficacy plasma molsidomine concentration of 5 µg/L; (iii) to demonstrate a possible bioequivalence between 8mg twice-daily and 16mg once-daily tablets when used at their recommended therapeutic dosage regimen; and (iv) to assess the effect of food and age on the absorption, distribution, and elimination of the new once-daily formulation.

Methods

Different dosages of various formulations of molsidomine were administered to young and elderly healthy volunteers and plasma concentrations of molsidomine and its active metabolite, linsidomine (SIN-1), were determined. Plasma concentrations were determined using solid-phase extraction and enrichment of the extracts on a short column followed by elution of the analytes by liquid Chromatographic mobile phase and ultraviolet detection.

Results

Compared with previous formulations, molsidomine 16mg once daily showed an increased time to maximum plasma concentration and a tendency to a lower mean maximum plasma concentration. Plasma molsidomine concentrations were always above the efficacy threshold of 5 µg/L during the whole 24-hour cycle and the concentration at trough was still in the therapeutic range. No drug accumulation was observed after repeated administration. Bioequivalence between molsidomine 16mg once daily and molsidomine 8mg twice daily could not be demonstrated after 1 and 5 days of treatment, the relative bioavailability being significantly larger with the latter regimen. Pharmacokinetics of molsidomine 16mg once daily was not significantly affected by either concomitant food ingestion (no major effect of a high-fat meal) or aging (no major difference between young and elderly healthy volunteers).

Conclusions

Molsidomine 16mg once daily allowed the maintenance of a therapeutically active plasma concentration over 24 hours after single or repeated oral administration. The bioavailability of molsidomine from the once-daily preparation is apparently not affected by concomitant administration of food or age of the recipient.     

Use of In Vitro�CIn Vivo Correlation to Predict the Pharmacokinetics of Several Products Containing a BCS Class 1 Drug in Extended Release Matrices

Purpose

To determine if an IVIVC model can predict PK profiles of varying formulations of a BCS Class 1 drug that is a salt of a weak base.

Method

An IVIVC model (Level A) was created by correlating deconvoluted in vivo absorption data obtained from oral administration of 50?mg, 100?mg, and 200?mg fast and slow extended release formulations with in vitro percent dissolved using residual regression analysis. The model was then used to predict the in vivo profile of five test products that varied in formulation characteristics.

Results

The model passed internal validation for predicted Cmax and AUC. For external validation, in vitro data of five different test formulations was utilized. The model passed external validation for two test formulations that were different but belonging to the same release mechanism as that of the reference formulation. Three formulations failed external validation because they belonged to either a mixed or different release mechanism. The model and results were further confirmed using GatstroPlus? simulation software.

Conclusions

These observations indicate that an IVIVC model for a BCS class I drug may be applicable to varying formulations if the principle of the drug release is similar.     

Adherence with levodopa/carbidopa/entacapone versus levodopa/carbidopa and entacapone as separate tablets in patients with Parkinson’s disease

Abstract

Background:

Observational studies suggest that single-tablet formulations are associated with improved adherence versus the same components taken as separate tablets. The objective of this study was to compare adherence in patients with Parkinson’s disease (PD) receiving levodopa therapy as levodopa/carbidopa/entacapone tablets (LCE) versus levodopa/carbidopa (LC) tablets and entacapone (E) as separate tablets (LC and E).     

Synthesis and anti-proliferative activity evaluation of N3-acyl-N5-aryl-3,5-diaminoindazole analogues as anti-head and neck cancer agent

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells. Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.     

Ingestion of a denture cleanser: Did it cause gastric perforation?

Introduction

Human ingestion of denture cleansers leading to gastric perforation has not previously been described.

Case Report

A 27-year-old male ingested three denture cleanser tablets in water over two days in an attempt to cause a false-negative result on a workplace urine drug screen. Seven days later he presented to an emergency department with a perforated gastric ulcer.

Discussion

A literature review of cases and the chemistry of the components of his ingestion was conducted to determine the possible relationship between these events. Ingestion of intact fragments of the tablets would be likely to result in significant gastric toxicity, but ingestion of dissolved tablets would be unlikely to have caused his illness.     

Knowledge,attitudes and beliefs of patients and carers regarding medication adherence: a review of qualitative literature

Purpose

The aim of this review is to cohere evidence on the knowledge, attitudes and beliefs of patients and carers regarding medication adherence. Medication adherence refers to “the extent to which the patient’s action matches the agreed recommendations”. Medication adherence is vital in preventing, managing and curing illnesses and, hence, is linked with positive health outcomes.

Methods

A search was conducted using the following databases: CINAHL, Embase, PubMed and Web of Knowledge from inception to November 2013. Titles and abstracts were screened for inclusion in the review according to pre-defined inclusion and exclusion criteria. Studies were assessed for quality, and data were extracted into a data extraction form. Results were analysed thematically.

Results

The final results included 34 articles. Eight analytical themes were identified: (i) beliefs and experiences of medicines, (ii) family support and culture, (iii) role of and relationship with health-care practitioners, (iv) factors related to the disease, (v) self-regulation, (vi) communication, (vii) cost and (viii) access. The theme, “beliefs and experiences of medicines”, was present in 33 studies, with many discussing the influence that side effects have on medication adherence.

Conclusions

There are a number of variables that impact upon the knowledge, attitudes and beliefs of patients and carers regarding medication adherence. This review presents an overview of the analytical themes which offers the opportunity to examine interventions and their relative efficacies to increase medication adherence.     

Linear Delivery of Verapamil via Nanofibrous Sheet-Based System

Purpose

To achieve linear delivery of a highly water-soluble oral drug, verapamil, with a nanofibrous sheet-based system.

Methods

The nanofibrous sheets made of poly (lactic-co-glycolic acid) were used as a diffusion barrier to cap a tablet containing verapamil. For controlled drug delivery, we varied the sheet thickness to 20???m, 50???m and 80???m to give the capped drug tablets, 20CT, 50CT and 80CT, respectively.

Results

Drug release was more sustained as the sheet thickness increased. Thus, the periods for almost complete drug release could be extended up to 14?h with the 80???m-thick sheets. As we assessed the linear least square fits to the in vitro drug release data from the capped tablets, 20CT and 50CT showed a fairly good correlation with linear release. The periods of linear release were 6?h and 8?h for 20CT and 50CT, respectively, both releasing more than 85% drug during this period.

Conclusion

We conclude that a drug tablet capped with nanofibrous sheets is a promising system for linear delivery of a highly water-soluble oral drug.     

Persistence with pharmacological treatment in the specialist mental healthcare of patients with severe mental disorders

Purpose

The aim of this study was to measure persistence with pharmacological treatment in the specialist mental healthcare of patients with schizophrenia, bipolar disorder, and unipolar depression in Lombardy, a region of 10 million inhabitants located in the northernmost part of Italy.

Methods

The data concerning psychiatric care used in this study were retrieved from the regional Psychiatric Information System, while information on drug treatment was retrieved from the regional administrative database. Time to lack of persistence with initial pharmacological treatment was the outcome measure.

Results

A total of 11,797 patients, followed in the specialist mental healthcare system, started a new pharmacological treatment for depression, schizophrenia, or bipolar disorder during 2007. Overall, 8,500 patients (72.1%) discontinued treatment during the 12?month follow-up, with a median duration of 101?days. Very similar discontinuation rates were observed in patients with unipolar depression, schizophrenia, and bipolar disorder. In the multivariate analysis, operational definitions of continuity and intensity of care were the most robust determinants of persistence with drug treatment in each of the three cohorts of psychiatric diagnoses.

Conclusions

High rates of treatment discontinuation were found in a population of patients with severe mental disorders followed in the specialist mental healthcare system of an Italian region, with no differences among patients with unipolar major depression, schizophrenia, and bipolar disorder. These findings corroborate the notion that the problem of treatment discontinuation in psychiatric disorders is a factor related to the capacity of the mental health system to assure and maintain continuity and intensity of care.     

A new synthetic varacin analogue, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), decreased hereditary catalepsy and increased the BDNF gene expression in the hippocampus in mice

Rationale

The creation of effective psychotropic drugs is the key problem of psychopharmacology. Natural compounds and their synthetic analogues attract particular attention.

Objectives

The effect of a new synthetic analogue of varacin, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), on the behavior and the expression of the genes coding BDNF (Brain-Derived Neurotrophic Factor, Bdnf) and CREB (cAMP response element-binding protein, Creb) implicated in the mechanism of psychotropic drug action as well as gp130 (Il6st) implicated in the mechanism of hereditary catalepsy in the brain of mice of ASC (Antidepressant Sensitive Catalepsy) strain was studied.

Results

Acute per os administration of 20 or 40?mg/kg, but not 10?mg/kg of TC-2153 significantly decreased catalepsy. At the same time, in the open field test, 10 or 20?mg/kg of TC-2153 did not influence the locomotor activity, grooming or time spent in the center, while the highest dose of the drug (40?mg/kg) significantly reduced time in the center without any effect on locomotion and grooming. Chronic TC-2153 treatment (10?mg/kg for 12?C16?days) did not influence the behavior in the open field but significantly attenuated catalepsy, increased Bdnf mRNA and decreased Il6st mRNA levels in the hippocampus.

Conclusions

The results suggest: 1) TC-2153 as a new drug with potential psychotropic and anticataleptic activities and 2) the involvement of BDNF and gp130 in the molecular mechanism of TC-2153 action.