In 1997, we published a review in PharmacoEconomics about quality of life (QOL) measurement in patients with schizophrenia. The objective of this article is to provide an update, as well as to ...revisit the development of the construct of QOL and its measurement as applied to schizophrenia. Since our previous article, there has been significant growth in the number of publications about QOL in schizophrenia. Unfortunately, alongside this significant increase in research interest, a number of concerns have also risen about the limitations and lack of impact the concept of QOL has on clinical care and health-policy decision making. A number of concerns previously outlined (such as lack of consensus on a uniform definition of QOL) continue to be an issue. However, we believe that a uniform definition may not be possible, and instead, it may be preferable to have several definitions, which may enrich the concept and broaden its usefulness. Some of the scales we reviewed in 1997 continue to be in use, while others are now rarely or never used. New scales with better psychometrics have been introduced, but most are without theoretical or conceptual foundation. On the other hand, the field of scaling in general has been changing over the past few years and is moving towards a new approach for scale development, based on item response theory, item banks and computer adaptive testing. Unfortunately, this has not extended to QOL in schizophrenia. There continues to be a dearth of theoretical and conceptual models for QOL in schizophrenia, which seems to create the perception that the construct lacks a good theoretical and scientific foundation. One of the major gaps identified in this review is the recognized lack of impact of QOL measurements on clinical management or policy decision making. The majority of publications continue to focus on measurement rather than what to do with the data. The lack of strategies to integrate QOL data in clinical care, as well as the failure to contribute to policy decisions, particularly in cost analysis or resource allocations, has created the perception that the construct of QOL in schizophrenia is not that useful. It is evident that, for QOL in schizophrenia to regain its promise, researchers must take the ultimate next step beyond measurement: to develop credible strategies for integrating QOL data in clinical practice. Additionally, more focused research is needed to demonstrate the role of QOL, not only as an outcome in itself but also as a contributor to other outcomes, such as adherence to medications, more satisfaction, less resource utilization and so on. Since self-appraisal of QOL does not happen in a vacuum but relates to the total human experience in all its biological, psychosocial and environmental aspects, particular attention must also be focused on important neurobiological dimensions such as affect and cognition. Both are significantly affected by the illness itself and its treatment.
Chlorpromazine versus placebo for schizophrenia Adams, Clive E; Awad, George A; Rathbone, John ...
Cochrane database of systematic reviews,
01/2014, Letnik:
2015, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Background
Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.
Objectives
To review the effects of chlorpromazine compared with placebo, for the ...treatment of schizophrenia.
Search methods
We searched the Cochrane Schizophrenia Group’s Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.
Selection criteria
We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non‐affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.
Data collection and analysis
We independently inspected citations and s, ordered papers, re‐inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95% confidence interval (CI) around this. We excluded continuous data if more than 50% of participants were lost to follow‐up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95% confidence interval. We used a fixed‐effect model.
Main results
We inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow‐up (n=512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n=1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early ( n=1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n=1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n=1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n=1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n=165, 5 RCTs, RR 4.92 CI 2.32 to 10.43).
Authors' conclusions
The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well‐established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence‐based decision making by clinicians, carers and patients.
Over the past two decades there has been increasing interest in including patients' self-reports in the management of their illness. Among the many reasons for such recent interest has been a rising ...consumer movement over the past few decades, which has led patients, their caregivers and their families to press for more meaningful sharing with physicians in the clinical decision-making process, with the clear expectations of better therapies and improved outcomes. Patients as consumers of services, their views, attitudes towards healthcare, as well as their level of satisfaction with care, have become increasingly recognized. The recent interest by the US Food and Drug Administration (FDA), as well as other regulatory agencies, in patient-reported outcomes (PROs) in the process of developing and testing new antipsychotics, has also added more impetus. It is clear that including patients in the decision-making process about the management of their psychiatric conditions also broadens the concept of 'recovery', by empowering patients to be active participants and gives a clear message that successful treatment in schizophrenia is more than a symptomatic improvement, but also includes improved functional status. Additionally, the recent interest in personalized medicine puts the patient in the centre of such development. Since 2004, when we published our review about the impact of new antipsychotics on quality of life in CNS Drugs, a number of newer antipsychotics have been introduced and include ziprasidone, aripiprazole, paliperidone, asenapine, iloperidone and lurasidone. The current review is based on 31 selected publications that cover the years 2004-2012, and deals with the impact of such newer antipsychotics on specific domains of PROs, such as subjective tolerability, quality of life, medication preference, satisfaction and social functioning. Most of the available data deal with ziprasidone, aripiprazole and paliperidone. Though the great majority of the studies indicate the newer antipsychotics have favourably impacted on aspects of PROs, such a conclusion can only be considered a trend due to the many design and methodological limitations of many of these studies. It is interesting to note, as the field awaits more rigorous studies, that there seems to be a unifying core that exists among the various subjective outcomes and that tends to generalize from one subjective outcome to other subjective outcomes. The patient who experiences good subjective tolerability to medications tends generally to be more satisfied and has a strong medication preference. The identification of such a unifying core can prove helpful, not only in the development of appropriate scales, but also in informing and guiding the process of development of new antipsychotics.
Although medication adherence and health-related quality of life (HRQoL) are two different outcome measures, it is believed that adherence to medication leads to an improvement in overall HRQoL. The ...study aimed to evaluate the association between medication adherence and HRQoL.
A questionnaire-based cross-sectional study design was undertaken with hypertension patients attending public hospitals in Quetta city, Pakistan. HRQoL was measured by Euroqol EQ-5D. Medication adherence was assessed by the Drug Attitude Inventory. Descriptive statistics was used to tabulate demographic and disease-related information. Spearmans correlation was used to assess the association between the study variables. All analysis was performed using SPSS 17.0.
Among 385 study patients, the mean age (SD) was 39.02 (6.59), with 68.8% of males dominating the entire cohort. The mean (SD) duration of hypertension was 3.010.939years. Forty percent (n=154) had a bachelors degree level of education with 34.8% (n=134) working in the private sector. A negative and weak correlation (0.77) between medication adherence and EQ-5D was reported. In addition, a negative weak correlation (0.120) was observed among medication adherence and EQ-VAS.
Correlations among the study variables were negligible and negative. Hence, there is no apparent relationship between the variables.
Schizophrenia is a long-term psychiatric disorder that impacts important mental functions and requires indefinite treatment, as well as psychosocial and economic support. The introduction of ...chlorpromazine, the first antipsychotic, and the subsequent development of a long list of similar dopamine-blocking antipsychotic medications, has changed the treatment of schizophrenia as medications have become the cornerstone of clinical management. The enthusiasm that greeted the introduction of antipsychotics was soon tempered by the realisation that they induced significant side effects, such as extrapyramidal and autonomic symptoms. A less-recognized side effect at the time was the emergence of subtle subjective side effects that led patients to dislike medications and eventually discontinue them, with serious consequences of frequent relapses requiring hospitalization, poor outcomes and more health costs. The development of our dedicated programme for research into subjective tolerability to medications over the past 30 years has allowed us to establish the validity of the construct of 'subjective tolerability' to antipsychotics, applying research methodologies that are required for any scientific inquiry. We clarified definitions, developed reliable measuring tools, and constructed psychosocial and neurobiological conceptual models. We also documented the serious consequences of negative subjective tolerability to antipsychotics: poor medication adherence behaviour, impaired quality of life, and worse clinical and functional outcomes. More recently, using neuroimaging techniques, we and other international research groups were able to clearly elucidate the neurobiology of dysphoric negative subjective responses, linking it to low dopamine functioning in the striatal region of the brain. Such a discovery for the first time allowed us to also link the development of comorbid drug abuse in schizophrenia, which is a common occurrence, to the development of neuroleptic dysphoria, since both relate to the low dopamine function in the striatum. As an already validated scientific concept that has serious consequences, subjective tolerability to antipsychotics can serve as a model for patient-centered outcomes that really matter. Our long-serving research programme also illustrates the value of clinical observations to the development of important clinical research studies, i.e. from the bedside to the research bench, and back to the bedside.
Abstract The Reasons for Antipsychotic Discontinuation Questionnaire (RAD-Q) was designed to assess clinicians' perceptions of reasons for antipsychotic discontinuation or continuation. The current ...study examined psychometric properties of this instrument and patterns of antipsychotic discontinuation. The sample of 121 patients (81 discontinuation, 40 continuation) with schizophrenia or schizoaffective disorder was 66.9% male, with a mean age of 41.6 years. Treating clinicians reported a mean of 4.1 reasons for discontinuation and 7.5 reasons for continuation. RAD-Q domain scores were derived to quantify the impact of three factors on the decision to discontinue or continue: treatment benefits, adverse events, and distal reasons other than direct effects of the medication. Analysis of inter-rater reliability indicated an acceptable degree of agreement between clinicians (weighted Kappa for discontinuation scores=0.70–0.78). Correlations with symptom measures (Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Positive and Negative Syndrome Scale (PANSS)) supported convergent validity of the benefits domain score ( r =0.28–0.47; all p <0.05). Domain scores discriminated among groups of patients differing in clinician and patient-reported clinical variables. Results suggest that the RAD-Q is a useful detailed measure of reasons for antipsychotic discontinuation and continuation. Findings indicate that clinicians usually report multiple reasons for discontinuation, rather than a single reason for each patient.
Schizophrenia is a disabling, chronic psychiatric disorder that poses numerous challenges in its management and consequences. It extols a significant cost to the patient in terms of personal ...suffering, on the caregiver as a result of the shift of burden of care from hospital to families, and on society at large in terms of significant direct and indirect costs that include frequent hospitalizations and the need for long-term psychosocial and economic support, as well as life-time lost productivity. 'Burden of care' is a complex construct that challenges simple definition, and is frequently criticized for being broad and generally negative. Frequently, burden of care is more defined by its impacts and consequences on caregivers. In addition to the emotional, psychological, physical and economic impact, the concept of 'burden of care' involves subtle but distressing notions such as shame, embarrassment, feelings of guilt and self-blame. The early conceptualization of 'burden of care' into two distinct components (objective and subjective) has guided research efforts until the present time. Objective burden of care is meant to indicate its effects on the household such as taking care of daily tasks, whereas subjective burden indicates the extent to which the caregivers perceive the burden of care. Research contributions in later years (1980s to the present) have added more depth to understanding of the construct of burden of care by exploring important determinants and factors that likely contribute or mediate the caregiver's perception of burden of care. Several studies examined the role of gender, and reported that relatives of male patients with schizophrenia frequently experience more social dysfunction and disabilities than those of female patients. Similarly, a number of other studies documented the contribution of ethnicity and cultural issues to subjective burden of care. Although there is no complete agreement on whether a specific cluster of psychotic symptoms has the most impact on a caregiver's burden of care, there is agreement that the severity of symptoms increases it. An extensive literature concerning family interventions in schizophrenia has demonstrated the positive impact of various family interventions in improving family environment, reducing relapse and easing the burden of care. Although the evidence of such positive impact of family interventions in schizophrenia is well documented, such interventions are neither widely used nor appropriately integrated in care plans, and are frequently underfunded. Although the cost of caregiving is considered to be significant, there are no reliable estimates of the costs associated with such care. The majority of available literature categorized the cost of burden of care among the indirect costs of schizophrenia in general. In recent years, attempts to compare the costs of caregiving in several countries have been reported in the evolving literature on this topic. 'Burden of care' as a complex construct certainly requires the development of appropriate methodology for its costing. In achieving a balance between the patients' and caregivers' perspectives, caregivers have to be included in the care plan and adequate information and support extended to the family and caregivers. Access to better treatment for patients, including medications, psychosocial interventions and rehabilitation services, are important basic elements in easing the burden on caregivers. Other measures such as availability of crisis management, provision of legally mandated community treatment to avert hospitalization, and well informed and balanced advocacy are also important. Although research efforts have been expanded in the last 3 decades, an urgent need exists for enhancing such efforts, particularly in the development and evaluation of effective family interventions strategies. There is also a need for continued improvement in the delivery of psychiatric services to the severely psychiatrically ill and their families. As there is a lack of reliable cost information about the family burden of care specific to schizophrenia, there is an urgent need to develop reliable approaches that can generate data that can inform in policy making and organization of services.
Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; ...this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.
We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.
Fifty RCTs from 1955-2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.
It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.
The recent emphasis of including patient reports in their own care management is reviewed in terms of the factors that contributed to its popularity. The role change of patients as being active ...participants in their own care as a result of the rising consumerism and advocacy has led to increased pressures for including patients in the therapeutic decision-making process. As consumers of clinical services, their perspectives and attitudes towards health and illness acquired more importance. The rising cost of healthcare has added another dimension in cost containment by empowering patients and sharing responsibility in their recovery, which hopefully can improve outcomes. Challenges in the development and implementation of patient-reported outcomes in psychiatry are reviewed and include the still unresolved subjective/objective dichotomy, identification of the most appropriate and relevant patient-reported outcomes. Few outcomes are identified and include: subjective tolerability of medication, self-reported health-related quality of life, preferences, patients' attitudes towards health and illness, satisfaction with medication and overall satisfaction of quality of care, and functional state, with particular focus on social functioning.
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