Lakshmi N. P. Voruganti

The Burden of Schizophrenia on Caregivers: A Review

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.

Impact of Atypical Antipsychotics on Quality of Life in Patients with Schizophrenia

Schizophrenia is a long-term disabling illness that affects approximately 1% of the population. Its course is generally chronic with acute psychotic exacerbations that may require frequent hospitalisations. The clinical picture includes a range of symptoms such as delusions, hallucinations, agitation, suspiciousness, hostility, conceptual disorganisation, blunted affect, emotional and social withdrawal, lack of spontaneity, poverty of speech and a wide range of neurocognitive deficits. Over the past 50 years, antipsychotic medications have emerged as the cornerstone of management in concert with other important interventions, such as psychosocial and economic support and rehabilitation efforts. However, the unrivalled role of conventional antipsychotic medications has been continuously challenged by the wide range of adverse effects of these medications and their lack of usefulness in the treatment of neurocognitive deficits as well as deficit and negative symptoms. In addition, the lack of subjective tolerability of these agents and their negative impact on quality of life have complicated management for a large number of patients. Over the last 15 years, several new atypical antipsychotic medications have been introduced, including amisulpride, remoxipride, risperidone, sertindole, olanzapine, zotepine, quetiapine, ziprasidone and aripiprazole. In general, the new antipsychotics have shown themselves to be at least comparable in efficacy to conventional antipsychotics but with superior subjective tolerability and a more favourable adverse effect profile.The majority of quality of life studies involving new antipsychotic agents have evaluated the benefits of risperidone, olanzapine and clozapine; only a few studies have examined the effects of other new antipsychotics. While most of these studies have methodological and design limitations, the weight of evidence from them nevertheless points to a trend towards a more positive impact on quality of life with atypical agents.A number of recommendations can be made. First, more independent well designed and controlled studies are urgently needed to evaluate the effects of antipsychotic therapy on quality of life in patients with schizophrenia. New comparative studies should explore not only the differences between new and old antipsychotics but also identify any potential differences between individual new agents. The role of cost-effectiveness studies such as cost utility approaches in schizophrenia needs to be revisited, notwithstanding the fact that these types of studies have been reported to be feasible in schizophrenia. Finally, quality-of-life-based pharmacoeconomic studies of antipsychotic agents should not concentrate solely on cost reduction or containment, as it is likely that in order to maximise the benefits of new antipsychotic medications, greater expenditure on rehabilitation programmes and other support services will be necessary in the short-term at least.

New Antipsychotics, Compliance, Quality of Life, and Subjective Tolerability—Are Patients Better Off?

Objectives: This overview reviews the impact of second-generation antipsychotics on less frequently researched outcomes such as medication-adherence behaviour, quality of life, and subjective tolerability in patients with schizophrenia. Methods: We selectively reviewed recent literature and considered our own research and experiences in the field. Results: Most published studies about second-generation antipsychotics have dealt with issues related to efficacy and safety. So far, not many studies have focused on effectiveness in terms of such important outcomes as medication-adherence behaviour, quality of life, subjective tolerability, and overall satisfaction with treatment. Although most studies are inconclusive and their results are inconsistent—which has to do with several design and methodological limitations—there seems, on balance, to be a trend indicating superiority of second-generation, compared with first-generation, antipsychotics in improving medication-adherence behaviour and quality of life. The trend toward more favourable subjective tolerability and less frequent neuroleptic dysphoria seems to be relatively stronger. Conclusions: At present, the state of the art can only indicate a more favourable trend for second-generation antipsychotics in regard to improving medication adherence behaviour, quality of life, and subjective tolerability. It is surprising that such important outcomes, which are likely the defining factors in the superiority of second-generation antipsychotics, have not received adequate research attention. Well-designed, controlled, and adequately powered studies are urgently needed before any firm conclusions can be reached.

Subjective and behavioural consequences of striatal dopamine depletion in schizophrenia — Findings from an in vivo SPECT study

Dysphoria is an integral part of the symptomatology of a variety of clinical states, though there is little empirical data available on the qualitative and quantitative aspects of this phenomenon. The purpose of the study was to administer alphamethyl paratyrosine (AMPT), a catecholamine depleting agent as a chemical probe to induce dysphoria, and document the ensuing changes in mental status. AMPT (4-5 g/day) was administered to a group of medication-free schizophrenic patients (n=13) over a 48 hour period, and changes in their mental status were monitored at 12 hour intervals with the Profile of Mood States (POMS), Addiction Research Center Inventory (ARCI), Drug Attitude Inventory (DAI) and other standardized rating scales. All of the subjects experienced dysphoric responses of variable severity. The profile of changes included blunted pleasure responsivity, clouded thinking, loss of motivation and lowered vigilance. Subtle subjective changes were experienced soon after the first dose of AMPT and the dysphoria steadily worsened, resulting in social withdrawal and personal distress. Subjective responses were the earliest to manifest, followed by akathisia, akinesia and rigidity. We conclude that AMPT induced dopamine depletion is a safe, rapid, reliable and reversible method of studying dysphoric states in humans. The technique is helpful in examining the phenomenology of dysphoria, the temporal relationship between subjective and behavioural consequences of dopamine depletion, and the role of dopamine in mediating subtle aspects of pleasure responsivity, which is in turn crucial to the understanding of treatment non-adherence in schizophrenia and the origins of comorbid substance abuse.

Going Beyond: An Adventure- and Recreation-Based Group Intervention Promotes Well-Being and Weight Loss in Schizophrenia:

Objective: To undertake a preliminary study to assess the feasibility of clinical implementation and evaluate the effectiveness of a novel adventure- and recreation-based group intervention in the rehabilitation of individuals with schizophrenia. Methods: In a 2-year, prospective, case–control study, 23 consecutively referred, clinically stabilized schizophrenia patients received the new intervention over an 8-month period; 31 patients on the wait list, considered the control group, received standard clinical care that included some recreational activities. Symptom severity, self-esteem, self-appraised cognitive abilities, and functioning were documented for both groups with standardized rating scales administered at baseline, on completion of treatment, and at 12 months posttreatment. Results: Treatment adherence was 97%, and there were no dropouts. Patients in the study group showed marginal improvement in perceived cognitive abilities and on domain-specific functioning measures but experienced a significant improvement in their self-esteem and global functioning (P < 0.05), as well as a weight loss of over 12 lb. Improvement was sustained over 1 year with further occupational and social gains. Conclusion: In the context of overcoming barriers to providing early intervention for youth and preventing metabolic problems among older adults with schizophrenia, adventure- and recreation-based interventions could play a useful complementary role.

Is neuroleptic dysphoria a variant of drug-induced extrapyramidal side effects?

Objectives: Neuroleptic drugs induce psychological side effects such as dysphoria, cognitive impairment, and loss of motivation. These side effects were largely underrecognized and trivialized in the past as variants of extrapyramidal side effects (EPSEs). We review the recent literature on the subject and clarify the relation between neuroleptic-induced dysphoria and EPSEs. Methods: We critically examined clinical, interventional, neuroimaging, and basic science studies published in the past 10 years, delineating the temporal, phenomenological, biochemical, and neuroanatomical relation between dysphoria and EPSEs. Results: Subjective responses occur within 4 to 6 hours of neuroleptic use, whereas acute dystonia is often observed within 24 hours and parkinsonian syndrome after 5 to 7 days. Neuroleptic-induced dopaminergic blockade mediates both dysphoria and EPSEs. However, impaired dopamine function in the nucleus accumbens seems to give rise to dysphoria, whereas blockade of D2 receptors in the nigrostriatal system is responsible for EPSEs. Conclusion: The earlier notion that neuroleptic dysphoria is a variant of EPSEs was simplistic and speculative. Exploring the differences rather than dwelling on the similarities will likely enhance our understanding of dopamines role in the origin of varied side effects and in their distinctive characteristics.

Insulin, Insulin-Like Growth Factors and Incretins : Neural Homeostatic Regulators and Treatment Opportunities

Mood disorders may be conceptualized as progressive neurodegenerative disorders associated with cognitive decline. Novel treatments capable of preserving and/or enhancing cognitive function represent an area of priority for research in the future.Insulin, insulin-like growth factor (IGF)-1 and incretins may play a critical role in both physiological and pathophysiological processes of the CNS. An emerging paradigm regarding the pathophysiology of mood disorders posits that alterations in biological networks that mediate stress compromise optimal neuronal and glial function. A growing body of evidence indicates that central administration of insulin may enhance cognitive function in both healthy and cognitively impaired individuals.The neuroactive peptides, insulin, IGF-1 and incretins, or agents that facilitate their central effects (e.g. insulin-sensitizing agents), may constitute novel and possibly disease-modifying neurocognitive treatments.

Antipsychotic Medications, Schizophrenia and the Issue of Quality of Life

Schizophrenia as a long term disabling illness generally runs a chronic course with acute psychotic relapses that frequently requires hospitalizations. Antipsychotic medications have emerged as the cornerstone in treatment of the disorder in addition to other important interventions such as rehabilitation, psychosocial and economic support. Unfortunately antipsychotic medications has presented a number of significant limitations in terms of inconveniencing or serious side effects as well as there inability to improve certain symptoms at different stages of the illness. 30{%} to 50{%} of patients on antipsychotic medications develop serious dislike to medication as a result of becoming dysphoric, a situation that lead to compromised adherence to medications and subsequent relapse and compromised quality of~life. ∈dent Reviewing published studies involving both new and old antipsychotic medications reveal a good deal of methodological limitations that make it difficult to reach any definitive conclusion about the impact of antipsychotic medications on quality of life. However, the weight of the evidence so far can only suggest a trend favouring the new antipsychotics in terms of their positive impact on quality of life. On the other hand it is clear that medications by themselves can not directly improve quality of life but certainly can improve the potential for patients to benefit from other important interventions such as rehabilitation and psychosocial support that can have direct impact on quality of life. A number of methodological and conceptual issues are proposed to improve the quality of quality of life studies. Finally, though quality of life by itself is an important outcome it is time for the field to look beyond quality of life measurements. In addition to being an outcome, quality of life improvement can be also construed as mediator of other important outcomes such as decreased relapse rate, re-hospitalization and medical resources utilization. Similarly, improvement in quality of life can enhance strategies for improving adherence to medications and other therapeutic regimens as well as better and longer tenure in the community

Role of Dopamine in Pleasure, Reward and Subjective Responses to Drugs

This chapter will attempt to accomplish a seemingly impossible task of characterizing the concept of quality of life in terms of pleasure centres, neuronal circuits and chemical mechanisms in the brain. The supporting explanations will be presented in three parts: first, identifying three key characteristics of quality of life – first, the central doctrine of subjectivity, the time frame of appraisal, and the relevance of immediate affective tone in determining quality of life ratings; second, a review of the cumulative knowledge on the neuroanatomical and neurochemical mechanisms underlying subjective responses to pleasurable stimuli such as food and drugs. Thirdly, evidence is presented to support that interference with these brain reward mechanisms leads to feelings of lack of pleasure and poor quality of life, citing antipsychotic drug therapy in schizophrenia as an example. Laboratory experiments in animals and neurochemical imaging studies in humans suggest that dopaminergic mechanisms in nucleus accumbens, amygdala, hippocampus and prefrontal cortex are key players in determining the qualitative and quantitative aspects of subjective responses to pleasurable stimuli. Antipsychotic drug induced dopaminergic blockade in these neuronal circuits leads to persistent feelings of dysphoria and pervasive lack of pleasure, leading to subjective distress and compromised quality of life. The nuances of subjective responses to antipsychotic drugs thus have enormous implications for long term care of the mentally ill people