Real-world evidence from a European cohort study of patients with treatment resistant depression: Healthcare resource utilization.

BACKGROUND: Treatment resistant depression (TRD) is diagnosed when patients experiencing a major depressive episode fail to respond to ≥2 treatments. Along with substantial indirect costs, patients with TRD have higher healthcare resource utilization (HCRU) than other patients with depression. However, research on the economic impact of this HCRU, and differences according to response to treatment, is lacking. METHODS: This multicenter, observational study documented HCRU among patients with TRD in European clinical practice initiating new antidepressant treatments. Data regarding access to outpatient consultations and other healthcare resources for the first 6 months, collected using a questionnaire, were analyzed qualitatively according to response and remission status. The economic impact of HCRU, estimated using European costing data, was analyzed quantitatively. RESULTS: Among 411 patients, average HCRU was higher in non-responders, attending five times more general practitioner (GP) consultations and spending longer in hospital (1.7 versus 1.1 days) than responders. Greater differences were observed according to remission status, with non-remitters attending seven times more GP consultations and spending approximately three times longer in hospital (1.7 versus 0.6 days) than remitters. Consequently, the estimated economic impacts of non-responders and non-remitters were significantly greater than those of responders and remitters, respectively. LIMITATIONS: Key limitations are small cohort size, absence of control groups and generalizability to different healthcare systems. CONCLUSION: Patients with TRD, particularly those not achieving remission, have considerable HCRU, with associated economic impact. The costs of unmet TRD treatment needs are thus substantial, and treatment success is fundamental to reduce individual needs and societal costs.

Self-reported burden of caregiver of adults with depression: a cross-sectional study in five Western European countries.

BACKGROUND: Caregiving in depression imposes a complex health and economic burden. Moreover, there is a paucity of studies examining the impact of caregiving for adult relatives with unipolar depression (CG-UD). This study assessed the burden among CG-UD in five western European (EUR5) countries (France, Germany, Italy, Spain and the United Kingdom) compared with caregivers of adults with other chronic comorbidities (CG-OD) and general non-caregiving (non-CG) population. METHODS: A retrospective observational study was conducted using the 2016 National Health and Wellness Survey (NHWS) in EUR5. Differences in humanistic burden (health status and health-related quality of life [HRQoL]) and economic burden (work productivity and activity impairments, health care resource utilization [HRU]) were assessed between CG-UD and CG-OD respondents. Caregiver-specific burden (caregiving responsibilities and caregiver reaction assessment [CRA]) was assessed between caregiver groups. Generalized linear models were used to compare between the groups on the outcomes after adjusting for potential confounders. RESULTS: Of the 77,418 survey respondents examined, 1380 identified as CG-UD, 6470 as CG-OD and 69,334 as non-CG. Compared to CG-OD and non-CG, CG-UD, reported significantly lower health status (e.g., EuroQoL-5 Dimensions-5 Levels [EQ-5D-5L]: CG-UD = 0.63, CG-OD = 0.67, and non-CG = 0.73, p < 0.001) and HRQoL (e.g., mental component score: CG-UD = 35.0, CG-OD = 37.8, and non-CG = 40.7, p < 0.001). Although effect sizes were small (d < 0.2), minimal clinically important differences (MCID) were apparent for HRQoL and health status. Increased economic-related burden was observed for work and activity impairment (e.g., absenteeism: CG-UD = 32.6%, CG-OD = 26.5%, and non-CG = 14.8%, p < 0.001) and HRU (e.g., healthcare provider [HCP; mean, past 6 months]: CG-UD = 10.5, CG-OD = 8.6, and non-CG = 6.8, p < 0.001). Caregiving-specific burden was associated with experiencing a greater lack of family support (CG-UD: 2.9 vs CG-OD: 2.8, p < 0.01), impact on finances (CG-UD: 3.0 vs CG-OD: 2.9, p = 0.036), and on the caregiver's schedule (CG-UD: 3.1 vs CG-OD: 3.0, p = 0.048). CONCLUSION: Caregivers of persons with chronic disease experience an excess humanistic and economic burden compared to the general population, with a greater burden confronting caregiver for adults with depression. These findings illustrate the far-reaching burden of depression on both the patient and the relatives who care for them.

Pharmacotherapeutic strategies for patients treated for depression in UK primary care: a database analysis.

OBJECTIVE: To investigate long-term patterns of antidepressant treatment in patients in primary care in the UK, and to assess their healthcare resource use and disease outcomes. RESEARCH DESIGN AND METHODS: A retrospective longitudinal cohort study was conducted using the Clinical Practice Research Datalink. The study population comprised patients aged ≥18 years with depression receiving a prescription for antidepressant monotherapy between 1 January 2006 and 31 December 2011 with no antidepressants within the preceding 6 months. Recovery was defined by timing of antidepressant prescriptions (≥6 months without treatment). Treatment lines and strategies (switching, combining, augmenting and resuming medication) were analyzed. Healthcare resource use for the different treatment strategies and periods of no therapy was assessed. RESULTS: Data from 123,662 patients (287,564 treatment lines) were analyzed. Switching and resumption of treatment were more frequent than other strategies. Recovery was highest with first-line monotherapy (45% of patients), while as a second-line strategy switching was more successful (43%) than combination or augmentation. In subsequent lines of treatment, switching was associated with successively lower rates of recovery (31% in the third line and 24% from the fourth line onwards). Similar rates were observed for resumption. Healthcare resource use was greater during antidepressant use than treatment-free periods. Augmentation was associated with the highest proportions of patients with a psychiatrist referral, psychologist referral and psychiatric hospitalization. CONCLUSIONS: This study provides extensive real-world information on the prescribing patterns and treatment outcomes for a large cohort of patients treated for depression with antidepressants in primary care. Switching is more frequently used than augmentation or combination treatment, with decreasing effectiveness across successive lines. Key limitations of the study were: (i) risk of selection bias due to the use of inclusion criteria based on depression diagnoses recorded by the practitioner; and (ii) reliance on prescribing patterns as proxies for clinical outcomes, such as recovery.

Cost-effectiveness of memantine in moderate and severe Alzheimer's disease in Norway.

BACKGROUND: The cost-effectiveness of memantine for the treatment of moderate and severe Alzheimer's disease has been assessed in several European countries. Objective of the study was to assess it in Norwegian settings. METHODS: This cost-utility analysis used a Markov modelling approach to simulate the evolution of patients until their need for full-time care (FTC) over a 5-year period. FTC was defined as a patient becoming either dependent or institutionalised. Transition probabilities were estimated using a newly developed predictive equation of time to FTC. Health resource use and utilities were obtained from the Scandinavian Study of Cost and Quality of Life in Alzheimer's Disease study, and mortality was obtained from the Oslo study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine with its alternative in this population, that is no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. The model underwent extensive sensitivity analyses. RESULTS: In Norway, memantine was found to delay the need for FTC by 4.4 weeks compared with standard care and was associated with increased quality-adjusted life years. Memantine was the dominant strategy with cost savings of €3739 (30 041 NOK) per patient. The probability of being the dominant strategy was 98.8%. This result was confirmed across multiple sensitivity analyses. CONCLUSIONS: The model suggests that memantine prolongs time to FTC for no additional cost to the healthcare system and society. It can be regarded as a cost-effective choice in the management of moderate and severe Alzheimer's disease.

Cost effectiveness of memantine in Alzheimer's disease in the UK.

OBJECTIVE: This analysis assesses the cost-effectiveness of memantine for the treatment of moderate-to-severe Alzheimer's disease (AD) in the UK. METHODS: This cost-utility analysis was based on a Markov model. The model simulated 5-year progress of patients with AD until they need full-time care (FTC), defined as a patient becoming either dependent or institutionalised. Transition probabilities were based on a predictive equation, derived from the London and South-East Region epidemiological study. Resource use, utilities and mortality were obtained from the same study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine to its alternative in the UK, i.e. no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. RESULTS: Memantine was found to delay the need to FTC by 6 weeks compared with current practice in the UK. It was associated with increased quality-adjusted life-years and cost savings to the healthcare system (probability of this outcome was 96%). The projections were made assuming that benefits from the 6-month treatment were sustained over time, which is regarded as the main limitation. The model underwent extensive sensitivity analyses, which confirmed the base-case findings. CONCLUSIONS: The model suggests that memantine delays the need for FTC and decreases cost. It can be regarded as a cost-effective choice in the management of moderate and severe AD.

Predicting time to full-time care in AD: a new model.

OBJECTIVE: To develop a model to predict the length of time before patients with Alzheimer's disease (AD) of varying severity require full-time care (FTC). METHODS: A predictive model (equation) of time to FTC (defined as being institutionalised or dependent) was developed based on the London and South-East Region (LASER-AD) epidemiological study using a discrete time representation of the Cox continuous time proportional hazards model and complementary log-log specification. RESULTS: Of the 117 pre-FTC patients, 68 (58.1%) patients progressed to FTC during the 54-month follow-up period. Analysis of potential predictors showed that baseline cognitive state, impairment of activities of daily living (ADL) and neuropsychiatric symptoms were strong predictors of time to FTC. In addition, the rate of cognitive and ADL decline predicted time to FTC. The final model predicted 88.2% of observations. CONCLUSION: The model simulates and predicts progression of pre-FTC AD patients until the need for FTC based on assessments for cognitive, functional and behavioural domains. The main application of the model is to assess the cost effectiveness of AD therapies as potential adjuncts to a background AD treatment including disease-modifying treatments. The applicability of the predictive model to a specific setting should be carefully assessed, i.e. the patient population being examined should have similar characteristics as patients in the LASER-AD cohort.

A dependency model for patients with Alzheimer's disease: its validation and relationship to the costs of care--the LASER-AD Study.

BACKGROUND: Loss of independence becomes more marked as Alzheimer's disease (AD) progresses and contributes significantly to its societal and economic burden. Existing measures of functional disability focus either on basic or on instrumental activities of daily living (ADL). It would be more appropriate to combine these but, using existing assessment tools, this would involve considerable quantitative analysis. Recently, a qualitative and pragmatic system of classifying AD patients according to levels of dependency has been developed in a Belgian cohort. OBJECTIVES: To validate independently, in a UK community setting, a functional classification model of AD patients and to explore the relationship between dependency and costs of care using this model. RESEARCH DESIGN AND METHODS: Longitudinal epidemiological study of 224 AD patients. Data were collected at baseline and at 6 months on ADL, global state, cognition, behavioural dimensions, depression, quality of life and resource utilisation using validated instruments. An automatic classification algorithm was performed to allow identification of dependency clusters. The scheme was tested for validity against other simultaneously collected data including health and social care costs. The relationship between dependency and costs of care was explored using ANOVA models. RESULTS: Analysis of the ADL assessment instruments produced three ADL sub-scores by which patients could be classified into one of three disability clusters: ('non-dependent', 'non-dependent with instrumental functional disability', and 'dependent'). Good external validity of the classification scheme was demonstrated by correlation with simultaneously collected data. After a backward selection process on ANOVA model (at a 5% level), institutionalisation and the most dependent status were the most significant cost drivers. CONCLUSIONS: Qualitative classification of AD patients using dependency levels is a simple and validated approach. Applying this approach showed that institutionalisation and the most 'dependent' status were independently and significantly associated with high care cost.

A new approach to the qualitative evaluation of functional disability in dementia.

BACKGROUND: Dementia patients suffer from the progressive deterioration of cognitive and functional abilities. Instrumental disabilities usually appear in the earlier stages of the disease while basic disabilities appear in the more advanced stages. In order to differentiate between mild, moderate and severe patients both instrumental and basic functional disabilities should be taken into account simultaneously. OBJECTIVES: The objective of this study was to find a new method for classifying dementia patients based on their disabilities by using a basic and an instrumental Activities of Daily Living (ADL) scale. METHODS: Functional disability was assessed in a Belgian cohort of dementia patients using the Katz and Lawton Instrumental Activities of Daily Living (IADL) scales. A k-means derived clustering method allocated patients to disability clusters according to their Katz and Lawton scores. In order to validate the classification, we compared socio-demographic, clinical and costs parameters between the groups. RESULTS: The clustering method allocated patients between three clusters: dependent, non-dependent with instrumental functional disability (ND-IFD) and non-dependent. Dependence, as defined by these clusters, significantly correlates with age, residential setting, MMSE, patient's quality of life and costs. CONCLUSION: This new classification of patients suffering from dementia will provide better understanding of functional disabilities and will complement the evaluation of disease severity based on cognitive function.