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Cost of disorders of the brain in Europe 2010

Cholinesterase Inhibitors in Alzheimer's Disease

Insomnia as a predictor of mental disorders: A systematic review and meta-analysis.

The basal ganglia (BG) are composed of several nuclei involved in neural processing related to the execution of motor, cognitive and emotional activities. Preclinical and clinical data have implicated a role for these structures in pain processing. Recently neuroimaging has added important information on BG activation in conditions of acute pain, chronic pain and as a result of drug effects. Our current understanding of alterations in cortical and sub-cortical regions in pain suggests that the BG are uniquely involved in thalamo-cortico-BG loops to integrate many aspects of pain. These include the integration of motor, emotional, autonomic and cognitive responses to pain.

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A key role of the basal ganglia in pain and analgesia - insights gained through human functional imaging

Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), which are thought to play a major role in inducing neuronal death. Both TNF-alpha and IL-1beta increase the permeability of the blood-brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca(2+) levels. Additionally, TNF-alpha co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-alpha and IL-1beta in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-alpha and IL-1beta on neuronal life and death in HAD is discussed.

Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia

Background The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. Methods This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. Results The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. Conclusion These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

/pdf/functional-impairment-in-patients-with-major-depressive-3879kyn5kh.pdf

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

RESULTS: Compared with citalopram, escitalopram-treated patients showed significantly higher response rates and increased mean change from baseline in MADRS at weeks 1 and 8. The superiority of escitalopram over citalopram was more pronounced in very severely depressed patients. This superiority was further shown to increase with degree of severity of the depression. The robustness of meta-analysis results was supported by sensitivity analyses. The clinical superiority of escitalopram versus citalopram is consistent with the results of preclinical pharmacological studies. CONCLUSION: Escitalopram was shown to be an effective therapeutic treatment for MDD, presenting significant advantages over citalopram. (Int J Psych Clin Pract 2003; 7: 259/268)

Comparison of escitalopram and citalopram efficacy: A meta-analysis

Background Major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQoL) and everyday functioning. This cohort study investigated the long-term development of HRQoL in patients with MDD and its association with patient characteristics, including depressive symptom severity and cognitive symptoms. Methods The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study was a longitudinal cohort study conducted in 1,159 outpatients aged 18-65 years with MDD in France, Germany, Spain, Sweden, and the UK. The patients were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. HRQoL was assessed using the Medical Outcomes Study Short-Form 12-item Health Survey (SF-12) up to month 12 and the EuroQol Five Dimensions questionnaire up to month 24 (UK only). Depressive symptom severity was assessed up to month 24 by the patient-reported Patient Health Questionnaire and cognitive symptoms by the Perceived Deficit Questionnaire. Multivariate analyses were performed to identify patient characteristics associated with HRQoL. Results Mental HRQoL was severely impaired at baseline versus normative data (mean [SD] SF-12 mental component summary [MCS], 26.5 [9.2]); mean (SD) physical component summary (PCS) total score was 45.2 (12.1). SF-12 MCS improved over 12 months of follow-up (38.7 [11.6] at month 12), while SF-12 PCS remained stable (45.3 [11.1]). At each assessment time point, there was a clear pattern of lower SF-12 MCS and PCS total score in patients experiencing greater cognitive problems. The mean EuroQol Five Dimensions questionnaire utility index score generally decreased (i.e., worsened) with increasing severity of cognitive and depressive symptoms at all time points up to 24 months. Multivariate analyses identified both depression severity and cognitive symptoms as strongly and significantly associated with poor HRQoL. Conclusion These findings highlight the importance of recognizing and managing residual symptoms in patients with MDD, including the cognitive symptoms, to restore long-term psychosocial functioning.

/pdf/long-term-follow-up-on-health-related-quality-of-life-in-4bxw8fsvc6.pdf

Long-term follow-up on health-related quality of life in major depressive disorder: a 2-year European cohort study

Psychometric Validation of Perceived Deficits Questionnaire – Depression (PDQ-D) in Patients with Major Depressive Disorder (MDD)

In patients with moderately severe to severe Alzheimer’s disease, the N-methyl-D-aspartate (NMDA) antagonist memantine has been shown to improve outcomes and to be associated with reductions in resource utilisation and total healthcare costs relative to no pharmacological intervention after 28 weeks in phase III clinical and pharmacoeconomic studies. However, the longer term cost implications of treatment with memantine are not known. To evaluate the effect of treatment with memantine in patients with moderately severe to severe Alzheimer’s disease on resource use and on cost and patient outcomes in Finland over a 5-year time horizon. A Markov model was constructed to simulate a patient’s progression through a finite series of health states with a time horizon of 5 years. The states were defined in terms of physical dependency, place of residency (community or institution), and cognitive function. Each 6-month Markov cycle was repeated ten times. A 5% rate was used to discount costs. Inputs for the model were derived from epidemiological data collected during the Kuopio 75+ Study, a Finnish population-based health survey of dementia and functional capacity among individuals aged ≥75 years. Costs were considered from a societal perspective. Probabilities used in the model, together with cost and resource use differences between treatment with memantine (Ebixa®, Namenda®, Axura®) and no pharmacological intervention, were derived from a randomised, double-blind, placebo-controlled clinical trial that included an economic assessment. This study enrolled 252 patients with moderately severe to severe Alzheimer’s disease. We took a conservative approach that assumed that the effectiveness of treatment with memantine was limited to 12 months’ duration. Monte Carlo simulations were performed to evaluate the effect of treatment with memantine on duration of independence and time to institutionalisation. Sensitivity analyses included memantine efficacy best- (5 years) and worst- (6 months) case scenarios, and an analysis in which 5% discounting was not applied. Memantine therapy was associated with approximately 4 extra months of independence, 1 additional month of residence in the community, and a cost reduction relative to placebo of approximately €1700 per patient over 5 years, despite the limiting of persistence of efficacy to 12 months (year of costing, 2001). Monte Carlo simulations and sensitivity analyses supported the findings. Conclusion: According to the model, over 5 years the additional drug costs of treating patients with moderately severe to severe Alzheimer’s disease with memantine were amply offset by cost savings related chiefly to increased independence and delayed institutionalisation.

B. Rive

Papers

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

Comparison of escitalopram and citalopram efficacy: A meta-analysis

Long-term follow-up on health-related quality of life in major depressive disorder: a 2-year European cohort study

Psychometric Validation of Perceived Deficits Questionnaire – Depression (PDQ-D) in Patients with Major Depressive Disorder (MDD)

Cost effectiveness of memantine in moderately severe to severe Alzheimer's disease : a markov model in Finland.