Assessing and Reporting the Adverse Effects of Antipsychotic Medication: A Systematic Review of Clinical Studies, and Prospective, Retrospective, and Cross-Sectional Research

Objective: Adverse effects (AEs) of antipsychotic medication have important implications for patients and prescribers in terms of wellbeing, treatment adherence and quality of life. This review summarises strategies for collecting and reporting AE data across a representative literature sample to ascertain their rigour and comprehensiveness. Methods: A PsycINFO search, following PRISMA Statement guidelines, was conducted in English-language journals (1980–July 2014) using the following search string: (antipsychotic* OR neuroleptic*) AND (subjective effect OR subjective experience OR subjective response OR subjective mental alterations OR subjective tolerability OR subjective wellbeing OR patient perspective OR self-rated effects OR adverse effects OR side-effects). Of 7,825 articles, 384 were retained that reported quantified results for AEs of typical or atypical antipsychotics amongst transdiagnostic adult, adolescent, and child populations. Information extracted included: types of AEs reported; how AEs were assessed; assessment duration; assessment of the global impact of antipsychotic consumption on wellbeing; and conflict of interest due to industry sponsorship. Results: Neurological, metabolic, and sedation-related cognitive effects were reported most systematically relative to affective, anticholinergic, autonomic, cutaneous, hormonal, miscellaneous, and non-sedative cognitive effects. The impact of AEs on patient wellbeing was poorly assessed. Cross-sectional and prospective research designs yielded more comprehensive data about AE severity and prevalence than clinical or observational retrospective studies. 3 Conclusions: AE detection and classification can be improved through the use of standardised assessment instruments and consideration of subjective patient impact. Observational research can supplement information from clinical trials to improve the ecological validity of AE data.

Medication use in pregnancy: a cross-sectional, multinational web-based study.

OBJECTIVES: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. DESIGN: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. SETTING: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. PARTICIPANTS: Pregnant women and new mothers with children less than 1 year of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. RESULTS: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. CONCLUSIONS: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.

The meaning of multiple medication use in adults: A qualitative study

Over half of prescribed medications are not taken as prescribed, resulting in health and economic consequences. Using constructivist grounded theory, 15 interviews were conducted to develop a theory on understanding the medication adherence choices of individuals, who were between the ages of 40 to 55, were diagnosed with a chronic condition, and taking three or more medications. The results indicate that participants are engaging in self-management strategies, with massive variance in adherence behaviours. Medications are sacrificed for personal and financial reasons, resonating with feelings of fear for the person’s current situation and future. Individuals are struggling with who they have become to who they once were, which becomes related to their medications. Finally, individuals are citing the impact of their physician; citing barriers to communication and Canada’s health care system. Participants’ experiences provided an understanding of the meanings individuals associate with their medications and how this impacts their decision-making.

Monitoring Drug Use Among HIV/AIDS Patients in Brazil: Should we Combine Self-Report and Urinalysis?

Illicit drug use in HIV-infected patients can be linked to impairment of physical and mental health, low health-related quality of life, and suboptimal adherence to HIV treatment. This study aimed to evaluate the correlation of self-report illicit drug use, urinalysis for cocaine and cannabis metabolites, and severity of dependence among HIV-infected patients on antiretroviral therapy (ART) in a treatment center in Brazil. Four hundred and thirty-eight outpatients of an HIV referral center were interviewed and assessed for drug use (lifetime, last year and last month). Urinalysis was performed to detect the presence of cocaine and cannabis metabolites in urine samples. Overall agreement between self-report and urinalysis was almost 68% for cannabis and higher than 85% for cocaine. Positive urinalysis was significantly associated with more than once a week cannabis (p < .0001) and cocaine (p <.0001) use during the last-month. Severity of Dependence Scale (SDS) properly predicted positive cocaine urinalysis results (area under the curve [AUC] = .81, p = .0001). Frequency of cannabis and cocaine use, SDS score degree and positive urinalysis for both drugs were correlated. Our findings suggest that positive self-report is a reliable predictor of positive urine sample both for cannabis and cocaine, but since the agreement was not perfect, there is a role for urine drug screening in the care of patients with HIV-related conditions.

Medication adherence in frail elderly outpatients with dementia

Since drug therapy in the elderly is complex and longterm and aged people commonly present some level of impairment and disability, medication adherence tend to decrease with age. Cognitive function is a key factor associated with medication adherence and professional or caregiver assistance may be necessary to maintain correct drug use. This study aims to analyze frail elderly outpatients aged 80 years or over diagnosed with dementia. The study is cross-sectional and is being conducted at the Ambulatory of Frailty of the University Hospital of the University of São Paulo (AF-UH). It is being based on information collected through an interview conducted with the patient or its caregiver. Medication adherence is assessed by the proportion of the prescribed drugs used in concordance with the prescription. Here it is presented the results of a pilot study. Thirty patients were included in the pilot study of which 23 (76.7%) were female and 7 (23.3%) males. The mean(SD) age, number of dwelling relatives, living children and prescribed drugs was, respectively, 86(5) years, 3(2), 3(2) and 6(3). The AF-UH consultation is the only regular physician encounter for 60.7% of the patients. Out of 30 patients, 5 (16.7%) live alone. Medication is a caregiver responsibility in 22 (73.4%) patients; the others (26.6%) self-administer their medicines. 13 (43.3%) of patients regularly use at least one drug not prescribed. Dementia was present in 8 patients all of which have a caregiver responsible for the management and,or the administration of the medicines; on the other hand, only 4 of the 22 nondemented patients (18.2%) have assistance of a caregiver (p<.001). The mean(SD) number of prescribed drugs was higher in nondemented patients [6.5(2.4)] than in those with dementia[3.5(2.3)] (p=.004). Educational level was similar between caregivers and patients (p=.503) as well as between caregivers of demented and non demented patients (p=.582). Among patients without dementia, those with caregiver assistance pre-presented the same mean(SD) medication adherence [0.93(0.14)] than those without it [0.78(0.28)] (p=.305). When compared to nondemented patients without caregivers, demented patients showed higher medication adherence [1.00(0.00)] (p=.013) since all of them used their drugs as recommended. The lower number of prescribed drugs and caregiver assistance seem to play an important role in the adherence of pharmacotherapy of demented patients in the studied population.

Use of modern and traditional products to self-treat symptoms of sexually transmitted infections in South African women

The objective of the study is to investigate products used by women self-treating symptoms of reproductive tract infections (RTIs), including sexually transmitted infections (STIs), and their methods of administration. A household survey using a multi-stage cluster sample design was undertaken in KwaZulu-Natal, South Africa. Women aged 18-60 years were interviewed (n = 867) and information was collected on demographics, reproductive health and sexual behaviours. A fifth of women reported having RTI/STI symptoms (20.5%), of whom 41.9% were treating these symptoms (mostly discharge [79.1%], ulcers [6.8%] and itching [7.7%]). Only three women were using medication prescribed by a health provider, while the remainder were self-treating using traditional medicines and modern products, including antiseptics, soaps, petroleum jelly, menthol creams and alum. Products were administered in various ways. Although RTI/STI treatment is widely available and free in public health facilities, many women are still self-treating. Potential harm of products for self-treatment requires further investigation and efforts should be made to improve STI service uptake.

Medication errors in a swiss cardiovascular surgery department: a cross-sectional study based on a novel medication error report method

The purpose of this study was (1) to determine frequency and type of medication errors (MEs), (2) to assess the number of MEs prevented by registered nurses, (3) to assess the consequences of ME for patients, and (4) to compare the number of MEs reported by a newly developed medication error self-reporting tool to the number reported by the traditional incident reporting system. We conducted a cross-sectional study on ME in the Cardiovascular Surgery Department of Bern University Hospital in Switzerland. Eligible registered nurses (n = 119) involving in the medication process were included. Data on ME were collected using an investigator-developed medication error self reporting tool (MESRT) that asked about the occurrence and characteristics of ME. Registered nurses were instructed to complete a MESRT at the end of each shift even if there was no ME. All MESRTs were completed anonymously. During the one-month study period, a total of 987 MESRTs were returned. Of the 987 completed MESRTs, 288 (29%) indicated that there had been an ME. Registered nurses reported preventing 49 (5%) MEs. Overall, eight (2.8%) MEs had patient consequences. The high response rate suggests that this new method may be a very effective approach to detect, report, and describe ME in hospitals.

Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients

BACKGROUND: The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound. METHODS: Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA <50 copies/ml over the previous 3 months and who were interviewed about adherence at least once prior to 1 March 2007 were eligible. Adherence was defined in terms of missed doses of cART (0, 1, 2 or >2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound. RESULTS: A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking <95% of doses 4.5% and missing > or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed. CONCLUSIONS: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.

Disparities in bone density measurement history and osteoporosis medication utilisation in Swiss women: results from the Swiss Health Survey 2007

BACKGROUND Although factors associated with the utilisation of bone density measurement (BDM) and osteoporosis treatment have been regularly assessed in the US and Canada, they have not been effectively analysed in European countries. This study assessed factors associated with the utilisation of BDM and osteoporosis medication (OM) in Switzerland. METHODS The Swiss Health Survey 2007 data included self-reported information on BDM and OM for women aged 40 years and older who were living in private households. Multivariable logistic regression analysis was used to identify sociodemographic, socioeconomic, healthcare-related and osteoporosis risk factors associated with BDM and OM utilisation. RESULTS The lifetime prevalence of BDM was 25.6% (95% CI: 24.3-26.9%) for women aged 40 years and older. BDM utilisation was associated with most sociodemographic factors, all the socioeconomic and healthcare-related factors, and with major osteoporosis risk factors analysed. The prevalence of current OM was 7.8% (95% CI: 7.0-8.6%) and it was associated with some sociodemographic and most healthcare-related factors but only with one socioeconomic factor. CONCLUSIONS In Swiss women, ever having had a BDM and current OM were low and utilisation disparities exist according to sociodemographic, socioeconomic and healthcare-related factors. This might foster further health inequalities. The reasons for these findings should be addressed in further studies of the elderly women, including those living in institutions.

A comparison of healthcare access, healthcare utilization and asthma self-management for Hispanic children in border and non-border regions of Texas

The purpose of this culminating experience was to investigate the relationships between healthcare utilization, insurance coverage, and socioeconomic characteristics of children with asthma along the Texas-Mexico Border. A secondary data analysis was conducted on cross-sectional data from the Texas Child Asthma Call-back Survey, a follow-up survey to the random digit dialed Behavior Risk Factor Surveillance Study (BRFSS) conducted between 2006-2009 ( n = 556 adults living in households with a child with asthma).^ The proportion of Hispanic children with asthma in Border areas of Texas was more than twice that of non-Border areas (84.8% vs. 28.8%). Parents in Border areas were less likely to have their own health insurance (OR = 0.251, 95% C.I. = 0.117-0.540) and less likely to complete the survey in English than Spanish (OR = 0.251 95% C.I. = 0.117-0.540) than parents in non-Border areas. No significant socio-economic or health care utilization differences were noted between Hispanic children living in Border areas compared to Hispanic children living in non-Border areas. Children with asthma along the Texas-Mexico Border, regardless of ethnicity and language, have insurance coverage rates, reported cost barriers to care, symptom management, and medication usage patterns similar to those in non-Border areas. When compared to English-speakers, Spanish-speaking parents in Texas as a whole are far less likely to be taught what to do during an asthma attack (50.2% vs. 78.6%).^ Language preference, rather than ethnicity or geographical residence, played a larger role on childhood asthma-related health disparities for children in Texas. Spanish-speaking parents in are less likely to receive adequate asthma self-management education. Investigating the effects of Hispanic acculturation rates and incongruent parent-child health insurance coverage may provide better insight into the health disparities of children along the Texas-Mexico Border.^

Relationships among epilepsy self-management, health outcomes, and socioeconomic status

The purpose of this study was to investigate the association between epilepsy self-management and disease control and socio-economic status. Study participants were adult patients at two epilepsy specialty clinics in Houston, Texas that serve demographically and socioeconomically diverse populations. Self-management behaviors- medication, information, safety, seizure, and lifestyle management were tested against emergency room visits, hospitalizations, and seizure occurrence. Overall self-management score was associated with a greater likelihood of hospitalizations over a prior twelve month time frame, but not for three months, and was not associated with seizure occurrence or emergency room visits, at all. Scores on specific self-management behaviors varied in their relationships to the different disease control indicators, over time. Contrary to expectations based on the findings of previous research, higher information management scores were associated with greater likelihood of emergency room visits and hospitalizations, over the study's twelve months. Higher lifestyle management scores were associated with lower likelihood of any emergency room visits, over the preceding twelve months and emergency room visits for the last three months. The positive associations between overall self-management scores and information management behaviors and disease control are contrary to published research. These findings may indicate that those with worse disease control in a prior period employ stronger self-management efforts to better control their epilepsy. Further research is needed to investigate this hypothesis.^

Predictors of benzodiazepine self -administration behavior in anxious patients

The purpose of this study was to examine factors that may be associated with benzodiazepine (BZ) self-administration and risks of dependence in anxious patients. Preliminary work included examination of psychosocial characteristics and subjective drug response as potential predictors of medication use. Fifty-five M, F patients with generalized anxiety or panic disorder participated in a 3-week outpatient Choice Procedure in which they self-medicated “as needed” with alprazolam (Alz) and placebo. Findings showed that a large amount of variance in alprazolam preference, frequency, and quantity of use could be predicted by measures of anxiety, drug liking, and certain personality characteristics. The primary study extended this work by examining whether individual differences in Alz sensitivity also predict patterns of use. Twenty anxious patients participated in the study, which required 11 weekly clinic visits. Ten of these also participated in a baseline assessment of HPA-axis function that involved 24-hour monitoring of cortisol and ACTH levels and a CRH Stimulation Test. This assessment was conducted on the basis of prior evidence that steroid metabolites exert neuromodulatory effects on the GABA A receptor and that HPA-axis function may be related to BZ sensitivity and long-term disability in anxious patients. Patients were classified as either HIGH or LOW users based on their p.r.n. patterns of Alz use during the first 3 weeks of the study. They then participated in a 4-week dose response trial in which they received prescribed doses of medication (placebo, 0.25, 0.5, and 1.0mg Alz), each taken TID for 1 week. The dose response trial was followed by a second 3-week Choice Procedure. Findings were not indicative of biological differences in Alz sensitivity between the HIGH and LOW users. However, the HIGH users had higher baseline anxiety and greater anxiolytic response to Alz than the LOW users. Anxiolytic benefits of p.r.n. and prescribed dosing were shown to be comparable, and patients' conservative patterns of p.r.n. medication use were not affected by the period of prescribed dosing. Although there was not strong evidence to suggest relationships between HPA-axis function and Alz use or sensitivity, interesting findings emerged about the relationship between HPA-axis function and anxiety. ^

Medication management at home: medication-related risk factors associated with poor health outcomes

Background: some patients may have medication-related risk factors only identified by home visits, but the extent to which those risk factors are associated with poor health outcomes remains unclear. Objective: to determine the association between medication-related risk factors and poor patient health outcomes from observations in the patients' homes. Design: cross-sectional study. Setting: patients' homes. Subjects: 204 general practice patients living in their own homes and at risk of medication-related poor health outcomes. Methods: medications and medication-related risk factors were identified in the patients' homes by community pharmacists and general practitioners (GPs). The medication-related risk factors were examined as determinants of patients' self-reported health related quality of life (SF-36) and their medication use, as well as physicians' impression of patient adverse drug events and health status. Results: key medication-related risk factors associated with poor health outcomes included: Lack of any medication administration routine, therapeutic duplication, hoarding, confusion between generic and trade names, multiple prescribers, discontinued medication repeats retained and multiple storage locations. Older age and female gender were associated with some poorer health outcomes. In addition, expired medication and poor adherence were also associated with poor health outcomes, however, not independently. Conclusion: the findings support the theory that polypharmacy and medication-related risk factors as a result of polypharmacy are correlated to poor health outcomes.

The Aston Medication Adherence Study:mapping the adherence patterns of an inner-city population

Background: The Aston Medication Adherence Study was designed to examine non-adherence to prescribed medicines within an inner-city population using general practice (GP) prescribing data. Objective: To examine non-adherence patterns to prescribed oralmedications within three chronic disease states and to compare differences in adherence levels between various patient groups to assist the routine identification of low adherence amongst patients within the Heart of Birmingham teaching Primary Care Trust (HoBtPCT). Setting: Patients within the area covered by HoBtPCT (England) prescribed medication for dyslipidaemia, type-2 diabetes and hypothyroidism, between 2000 and 2010 inclusively. HoBtPCT's population was disproportionately young,with seventy per cent of residents fromBlack and Minority Ethnic groups. Method: Systematic computational analysis of all medication issue data from 76 GP surgeries dichotomised patients into two groups (adherent and non-adherent) for each pharmacotherapeutic agent within the treatment groups. Dichotomised groupings were further analysed by recorded patient demographics to identify predictors of lower adherence levels. Results were compared to an analysis of a self-reportmeasure of adherence [using the Modified Morisky Scale© (MMAS-8)] and clinical value data (cholesterol values) from GP surgery records. Main outcome: Adherence levels for different patient demographics, for patients within specific longterm treatment groups. Results: Analysis within all three groups showed that for patients with the following characteristics, adherence levels were statistically lower than for others; patients: younger than 60 years of age; whose religion is coded as "Islam"; whose ethnicity is coded as one of the Asian groupings or as "Caribbean", "Other Black" and "African"; whose primary language is coded as "Urdu" or "Bengali"; and whose postcodes indicate that they live within the most socioeconomically deprived areas of HoBtPCT. Statistically significant correlations between adherence status and results from the selfreport measure of adherence and of clinical value data analysis were found. Conclusion: Using data fromGP prescribing systems, a computerised tool to calculate individual adherence levels for oral pharmacotherapy for the treatment of diabetes, dyslipidaemia and hypothyroidism has been developed.The tool has been used to establish nonadherence levels within the three treatment groups and the demographic characteristics indicative of lower adherence levels, which in turn will enable the targeting of interventional support within HoBtPCT. © Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2013.

Potential risk factors for medication non-adherence in patients with chronic obstructive pulmonary disease (COPD)

Aims - To investigate the effect of a range of demographic and psychosocial variables on medication adherence in chronic obstructive pulmonary disease (COPD) patients managed in a secondary care setting. Methods - A total of 173 patients with a confirmed diagnosis of COPD, recruited from an outpatient clinic in Northern Ireland, participated in the study. Data collection was carried out via face-to-face interviews and through review of patients’ medical charts. Social and demographic variables, co-morbidity, self-reported drug adherence (Morisky scale), Hospital Anxiety and Depression (HAD) scale, COPD knowledge, Health Belief Model (HBM) and self-efficacy scales were determined for each patient. Results - Participants were aged 67 ± 9.7 (mean ± SD) years, 56 % female and took a mean (SD) of 8.2 ± 3.4 drugs. Low adherence with medications was present in 29.5 % of the patients. Demographic variables (gender, age, marital status, living arrangements and occupation) were not associated with adherence. A range of clinical and psychosocial variables, on the other hand, were found to be associated with medication adherence, i.e. beliefs regarding medication effectiveness, severity of COPD, smoking status, presence of co-morbid illness, depressed mood, self-efficacy, perceived susceptibility and perceived barriers within the HBM (p < 0.05). Logistic regression analysis showed that perceived ineffectiveness of medication, presence of co-morbid illness, depressed mood and perceived barriers were independently associated with medication non-adherence in the study (P < 0.05). Conclusions - Adherence in COPD patients is influenced more by patients’ perception of their health and medication effectiveness, the presence of depressed mood and co-morbid illness than by demographic factors or disease severity.