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Patients with resistant epilepsy are often coprescribed multiple medications and are more likely to experience drug-drug interactions and adverse events (AEs). A new generation of antiepileptic drugs (AEDs) has been developed with improved safety/tolerability profiles. To evaluate the unmet treatment needs in epilepsy, a comprehensive search of the English-language literature was conducted on Medline and other databases using the terms "partial epilepsy" and "focal seizure," focusing on newer AEDs. Sixty-nine articles were identified. Most patients experienced AEs, which were generally mild-moderate in severity. Drug-drug interactions existed for 6 of 11 AEDs for which data were available. There is evidence for depressive symptoms being associated with zonisamide, and mood-stabilizing effects were shown for lamotrigine and pregabalin. Levetiracetam and eslicarbazepine improved cognitive function. Vigabatrin may increase the risk of developing psychosis. Health-related quality of life (HRQoL) was inversely correlated with seizure frequency. Discontinuation rates were often high, although treatment retention improved with slower dose titration. Adjunctive therapy with newer AEDs has the potential to enhance HRQoL and treatment continuation in patients with partial epilepsy. There remains room for improvement in the management of epilepsy, and better treatments and longer-term trials are needed to meet the special requirements of refractory patients.

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BACKGROUND: The direct cost burden of epilepsy in the US from a third-party payer perspective has not been evaluated. Furthermore, no study has quantified the indirect (work-loss) cost burden of epilepsy from an employer perspective in the US. OBJECTIVE: To assess the annual direct costs for privately insured US patients diagnosed with epilepsy, and indirect costs for a subset of employees from an employer perspective. METHODS: A retrospective analysis of a claims database for the privately insured, including employee disability claims from 1999 through 2005 and comprising 17 US companies, was conducted. A total of 4323 patients aged 16-64 years (including 1886 employees) with at least one epilepsy diagnosis (International Classification of Diseases, 9th edition, Clinical Modification [ICD-9-CM] code 345.x) over the period 1999-2004 were included. The control group was a demographically matched cohort of randomly chosen beneficiaries without an epilepsy diagnosis. All had continuous health coverage during 2004 (baseline) and 2005 (study period). Main outcome measures included annual direct (medical and pharmaceutical) costs and, for employees, indirect (disability and medically related absenteeism) and total costs for the study period. Wilcoxon rank-sum tests were used for univariate comparisons of annual direct costs, indirect costs (costs for the subset of employees with these data), and total (direct and indirect) costs during the study period. Two-part multivariate models that adjusted for patient characteristics were also used to compare costs between the study and control groups. RESULTS: Patients with epilepsy were an average age of 43 years and 57% were female. They had more co-morbidities than controls. On average, direct annual costs were significantly higher per patient with epilepsy than per control ($US10 258 vs $US3862, respectively; p < 0.0001) [year 2005 values], with an annual per-patient difference of $US6396. Epilepsy-related costs ($US2057) accounted for 20% of direct costs for patients with epilepsy. Annual indirect costs were significantly higher for employees with epilepsy than for employed controls ($US3192 vs $US1242, respectively; p < 0.0001), with a difference of $US1950. Total direct plus indirect costs for employees with epilepsy were also higher than those for employed controls ($US13 595 vs $US5338, respectively; p < 0.0001), with a difference of $US8257. CONCLUSIONS: Epilepsy was associated with significant economic burden. The excess direct costs in patients with epilepsy are underestimated when only epilepsy-related costs are considered.

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PURPOSE: Compare annual direct and indirect costs between privately insured U.S. patients with epileptic partial onset seizures (POS) and matched controls. METHODS: One thousand eight hundred fifty-nine patients (including a subset of 758 employees) with >or=1 (POS) diagnosis (ICD-9-CM: 345.4.x-345.7.x), 1999-2004, ages 16-64 years, were identified from a privately insured claims database. Control group was an age- and gender-matched cohort of randomly chosen beneficiaries without epilepsy (ICD-9-CM: 345.x). All were required to have continuous health coverage during 2004 (baseline) and 2005 (study period). Chi-square tests were used to compare baseline comorbidities. Univariate and multivariate analyses were used for comparisons of annual direct (medical and pharmaceutical) and indirect costs during the study period. RESULTS: Patients with POS were on average 42 years of age, and 57% were women. Patients with POS had significantly higher rates of mental health disorders, migraine, and other neurologic disorders, and higher Charlson comorbidity index (CCI) compared with controls. On average, direct annual costs were significantly higher for POS patients ($11,276) compared with controls ($4,087), p < 0.001; difference of $7,190. Epilepsy-related costs (i.e., costs for antiepileptic drugs, claims with epilepsy or convulsions diagnoses) accounted for $3,290 (29% of direct costs). Employees with POS had substantial and significantly higher indirect (disability- and medically related absenteeism) costs compared with controls ($3,431 vs. $1,511, p < 0.001). Multivariate analyses supported the matched-control univariate findings. CONCLUSION: Patients with POS had significantly higher costs compared with matched controls. Epilepsy-related costs underestimate the excess costs of patients with partial onset seizures.

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Schizophrenia is a chronic disease characterized by periods of relative stability interrupted by acute episodes (or relapses). The course of the disease may vary considerably between patients. Patient histories show considerable inter- and even intra-individual variability. We provide a critical assessment of the advantages and disadvantages of three modelling techniques that have been used in schizophrenia: decision trees, (cohort and micro-simulation) Markov models and discrete event simulation models. These modelling techniques are compared in terms of building time, data requirements, medico-scientific experience, simulation time, clinical representation, and their ability to deal with patient heterogeneity, the timing of events, prior events, patient interaction, interaction between co-variates and variability (first-order uncertainty). We note that, depending on the research question, the optimal modelling approach should be selected based on the expected differences between the comparators, the number of co-variates, the number of patient subgroups, the interactions between co-variates, and simulation time. Finally, it is argued that in case micro-simulation is required for the cost-effectiveness analysis of schizophrenia treatments, a discrete event simulation model is best suited to accurately capture all of the relevant interdependencies in this chronic, highly heterogeneous disease with limited long-term follow-up data.

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BACKGROUND: In 2002, the National Institute for Health and Clinical Excellence (NICE), recommended atypical antipsychotics over conventional ones for first-line schizophrenia treatment, based on their lower risk of extrapyramidal symptoms. OBJECTIVE: To estimate the incremental cost-effectiveness of atypical relative to conventional antipsychotics for the treatment of schizophrenia in the UK. METHODS: A discrete event simulation (DES) model was adopted to reflect the treatment of schizophrenia in the UK. The model estimates symptoms (using the Positive and Negative Symptom Score [PANSS]), psychiatrist visits, pharmacological treatment and treatment location, number and duration of psychotic relapses, level of compliance, quality-adjusted life-years (QALYs), and side effects over a 5-year time period. Probabilistic sensitivity analyses were carried out. Following NICE's "atypical" recommendation, the cost-effectiveness of atypical versus conventional antipsychotics was estimated in a scenario analysis, assuming both groups differ only in side-effect profile. RESULTS: When comparing conventional and atypical antipsychotics, the model predicts that the latter would decrease 5-year costs by 1633 Pound per patient and result in a QALY gain of 0.101. The probabilistic sensitivity analysis suggests these results are robust. The sensitivity analyses indicate that incremental costs and effects are most sensitive to the differential efficacy of atypicals and conventionals, as measured by PANSS. When it is assumed that the only differences between atypicals and conventionals are found in side-effect profiles, the incremental cost-effectiveness ratio of the atypicals is 45,000 Pound per QALY gained. CONCLUSION: According to this DES model for schizophrenia, atypical antipsychotics are cost-effective compared to the conventional antipsychotics. The assumptions used in the model need further validation through large naturalistic based studies with reasonable follow-up to determine the real-life differences between atypicals and conventional antipsychotics.

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BACKGROUND: Published methods for assessing remission in schizophrenia are variable and none have been definitively validated or standardized. Andreasen et al (2005) suggest systematic operational criteria using eight PANSS items for which patients must score < or = 3 (mild) for at least six months. METHODS: Using data from a one year, multi-site clinical trial (n = 675) remission criteria were compared to total PANSS scores and other endpoints and demonstrate excellent agreement with overall clinical status. RESULTS: Compared to total PANSS score of 60 points and other criteria, at time points > 6 months (8 and 12 months) the specificity of the remission criteria was 85%, i.e. of the patients who had a total score >60, 85% were classified as "not in remission." Sensitivity was also very high; 75% of patients with scores of <60 were classified as "in remission."Patients who dropped out of the trial were more likely not to be in remission prior to dropping out. CONCLUSION: These findings indicate that the remission criteria are both sensitive and specific indicators of clinical status. Additional analyses are required to determine if remission status predicts other outcomes, such as employment, independent living, and prognosis.

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Patients with schizophrenia suffer numerous relapses and rehospitalizations that are associated with high direct and indirect medical expense. Suboptimal therapeutic efficacy and, in particular, problems with compliance are major factors leading to relapse. Atypical antipsychotic agents offer improved efficacy and a lower rate of extrapyramidal adverse effects compared with conventional antipsychotic drugs. Long-acting intramuscular risperidone combines these benefits with improvements in compliance associated with depot injections. To assist decision making regarding the place of long-acting risperidone in therapy, a cost-effectiveness analysis of strategies involving first-line treatment with long-acting risperidone, oral olanzapine or depot haloperidol was performed from the perspective of the Belgian healthcare system. A decision tree model was created to compare the cost effectiveness of three first-line treatment strategies in a sample of young schizophrenic patients who had been treated for 1 year and whose disease had not been diagnosed for longer than 5 years. The model used a time horizon of 2 years, with health state transition probabilities, resource use and cost estimates derived from clinical trials, expert opinion and published prices. The four health states in the model were derived from an analysis of the literature. The principal efficacy measure was the proportion of patients successfully treated, defined as those who responded to initial treatment and who had none to two episodes of clinical deterioration without needing a change of treatment over the 2-year period. Comprehensive sensitivity analysis was carried out to test the robustness of the model. A greater proportion of patients were successfully treated with long-acting risperidone (82.7%) for 2 years, compared with those treated with olanzapine (74.8%) or haloperidol (57.3%). Total mean costs per patient over 2 years were 16,406 Euro with long-acting risperidone, 17,074 Euro with olanzapine and 21,779 Euro with haloperidol (year of costing 2003). The mean cost-effectiveness ratios were 19,839 Euro, 22,826 Euro and 38,008 Euro per successfully treated patient for long-acting risperidone, olanzapine and haloperidol, respectively. Results of the sensitivity analysis confirmed that the results were robust to a wide variation of different input variables (effectiveness, dosing distribution, patient status according to healthcare system). Long-acting risperidone was the dominant strategy, being both more effective and less costly than either oral olanzapine or depot haloperidol. Long-acting risperidone appears to represent a favourable first-line strategy for patients with schizophrenia requiring long-term maintenance treatment.

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BACKGROUND: BPD is a serious mental illness in which psychotherapy has been shown to improve patient outcomes and reduce the use of health services. In most studies of psychotherapy, lower use of health services has been taken to imply lower health service costs. However, the costs of psychotherapy can offset any cost savings due to reduced use of other health services. AIMS OF THE STUDY: To estimate the net costs of health service use in a group of BPD patients receiving intensive psychotherapy. METHODS: Data on use of inpatient hospital, emergency hospital, ambulatory care, diagnostic tests and medications were collected for the twelve months before psychotherapy and the twelve months after the completion of treatment. Cost estimates were developed using standardised unit costs. RESULTS: There was a saving of approximately $670,000 in health service use over the thirty patients compared to a cost of $130,000 for psychotherapy, giving a net cost saving of $18,000 per patient. Most of this was due to reduced hospital admissions. Cost saving was higher in those patients who were high users of hospital services. Sensitivity analyses were performed; overall, the findings consistently show a reduction in the cost of health services used. DISCUSSION: The group studied consisted of 30 patients and comprised a before/after design. Therefore it does not overcome criticisms of other work in this area, that is of observational studies and small sample sizes. Nonetheless, the results were based on detailed costing of service use, using conservative assumptions and subject to sensitivity analysis. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The use of intensive psychotherapy in BPD patients who are high users of health services, particularly those who have had multiple hospital admissions, is probably warranted until more evidence is available. IMPLICATIONS FOR HEALTH POLICIES: There is little rigorous evidence on the effectiveness and cost-effectiveness of psychotherapy. BPD patients appear to generate high service costs so it is important to establish effective and cost-effective modes of treatment. IMPLICATIONS FOR FURTHER RESEARCH: Further research is warranted to establish accurate patterns of service use in BPD patients, and to identify those groups who will most benefit from intensive psychotherapy. erans.