Lakshmi N.P. Voruganti

Measuring Quality of Life in Patients with Schizophrenia

In 1997, we published a review in Pharmaco Economics 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.

Cannabis induced dopamine release: an in-vivo SPECT study

In a research study aimed at examining the alterations in dopaminergic function in schizophrenia, the authors identified a surreptitious case scenario which provided new insights into the subjective and neurochemical effects of cannabis. A 38-year-old drug-free schizophrenic patient took part in a single photon emission computerized tomographic (SPECT) study of the brain, and smoked cannabis secretively during a pause in the course of an imaging session. Cannabis had an immediate calming effect, followed by a worsening of psychotic symptoms a few hours later. A comparison of the two sets of images, obtained before and immediately after smoking cannabis, indicated a 20% decrease in the striatal dopamine D2 receptor binding ratio, suggestive of increased synaptic dopaminergic activity. This observation offers a plausible biological explanation for the psychotogenic effects of cannabis in vulnerable individuals, and also raises speculations about an interaction between cannabinoid and dopaminergic systems in the brain reward pathways.

Subjective Effects of AMPT-induced Dopamine Depletion in Schizophrenia: Correlation between Dysphoric Responses and Striatal D2 Binding Ratios on SPECT Imaging

Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D2) function with 123IBZM-SPECT imaging. Results showed a wide variability in the occurrence and severity of dysphoric responses, clearly distinguishing a dysphoric group from non-dysphoric responders. Severity of dysphoric responses, measured by standardized rating scales, correlated inversely with changes in D2 receptor binding ratios (r = +0.82, p < .01). These results support the notion that striatal dopaminergic activity is not uniformly elevated in all schizophrenic patients, and the sub-group of individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic blocking drugs.

New generation antipsychotic drugs and compliance behaviour.

Purpose of review Antipsychotic therapy has been eclipsed by high rates of noncompliance; the problem was attributed to a lack of efficacy and the burden of side effects of neuroleptics. This review sought to examine whether the arrival of second generation (atypical) antipsychotic drugs with low side-effect liability and improved efficacy has helped to positively reinforce compliance behaviour among people treated for schizophrenia. Recent findings The number of studies that systematically examined compliance behaviour and its determinants during antipsychotic drug therapy is disappointingly low. A review of relevant clinical trials, drug dispensation databases and observational studies yielded equivocal results. The data have failed to substantiate the notion that novel antipsychotic drug use leads to improved medication compliance and favourable clinical outcomes. Summary A decade of clinical experience and research indicates that compliance behaviour has only marginally improved since the introduction of second generation antipsychotic drugs. Noncompliance in schizophrenia is a complex maladaptive pattern of behaviour determined by personal beliefs, illness-related factors, social attributes and health system variables. The reinforcing value of antipsychotic drugs may be less relevant in enhancing treatment compliance and influencing the natural history of schizophrenia.

The Aims of Antipsychotic Medication

SummaryThe aims of therapy with antipsychotic medications include effecti ve relief of symptoms without the induction of adverse effects, improved quality of life and cost effectiveness, and positive long term outcomes. However, currently available anti psychotics do not meet all of these requirements due to a number of well recognised limitations, such as a marked variability of response, induction of a wide range of adverse effects and a lack of subjective tolerability.A lack of response to antipsychotic medications occurs in up to 30% of patients and poses a particular challenge to clinicians. The reintroduction of clozapine for the treatment of patients with refractory schizophrenia has proven useful in a good number of patients, albeit with some risk of serious agranulocytosis and at a relatively high cost.Despite the extensive use of anti psychotics over the last 4 decades, little attention has been paid to the systematic evaluation of quality of life in patients with schizophrenia who receive medications, and in clinical trials of new agents. Similarly, there is a dearth of studies that have examined the cost effectiveness and cost utility of anti psychotics in terms of quality of life.In general, the aim of anti psychotics of alleviating psychotic symptoms without negatively affecting the functional status of patients has not been adequately, nor consistently, achieved with currently available agents. However, with the recent acceleration in the development of new antipsychotics, it is hoped that new drugs will soon be available which will prove to be more effective in treating more symptoms of schizophrenia and will be associated with fewer, or ideally no, adverse effects.

The Impact of Newer Atypical Antipsychotics on Patient-Reported Outcomes in Schizophrenia

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.