Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy.

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia. Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy. Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023. Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers. Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios. Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations. Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Cost-effectiveness analysis of HLA-B*15:02 screening before treatment of epilepsy in Indonesia.

INTRODUCTION: Adverse skin reactions due to drugs such as Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) occur in 3% of people receiving anti epileptic drugs (AED). Although SJS/TEN has a low incidence, the mortality and morbidity rates are high. Indonesia has not adopted HLA-B*1502 screening prior to administration of carbamazepine (CBZ), although previous studies found a relationship between HLA-B*1502 and SJS/TEN. METHODS: A hybrid decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed focal epilepsy: CBZ direct therapy, levetiracetam (LEV) direct therapy, and therapy based on HLA-B*15:02 test results. From a societal perspective, base case and sensitivity analyses were carried out over a lifetime. RESULTS: Direct administration of CBZ appears to have a slightly lower average cost than the HLA-B*15:02 allele screening strategy. The increase in quality-adjusted life year (QALY) in HLA-B*15:02 screening before treatment related to the cost difference reached 0.519 with an incremental cost-effectiveness ratio (ICER) of around USD 984 per unit of QALY acquisition. Direct treatment of LEV increased treatment costs by almost USD 2000 on average compared to the standard CBZ strategy. The increase in QALY is 0.834 in direct levetiracetam treatment, with an ICER of around USD 2230 for each QALY processing. CONCLUSION: Calculation of the cost-effectiveness of lifetime epilepsy therapy in this study found that the initial screening strategy with the HLA-B*15:02 test was the most cost-effective.

Cost-effectiveness of screening for HLA-B*1502 prior to initiation of carbamazepine in epilepsy patients of Asian ancestry in the United States.

OBJECTIVE: Carbamazepine, widely used in the treatment of partial and generalized tonic-clonic seizures, has been associated with life-threatening Stevens-Johnson syndrome/toxic epidermal necrolysis among some Asians. The HLA-B*1502 genotype that occurs with varying frequency among Asians is recommended for screening prior to starting carbamazepine. Our goal is to explore the cost-effectiveness of screening for the presence of this genetic allele. METHODS: We constructed a Markov model in a hypothetical cohort of adult Asian patients with epilepsy in the United States being considered for carbamazepine to investigate the cost-effectiveness of two alternative strategies: (1) no HLA-B*1502 gene allele screening and using carbamazepine and (2) HLA-B*1502 gene allele screening and starting levetiracetam in the case of a positive screen. RESULTS: For the lifetime horizon, HLA-B*1502 gene screening was the cost-effective choice compared to no gene screening, with an incremental cost-effectiveness ratio of $27 058 per quality-adjusted life-year (QALY), below the $50 000/QALY threshold in 99.69% of probabilistic sensitivity analyses. Although gene screening strategy was more expensive than a no screening strategy, it was more effective, yielding more QALYs, across all Asian ethnic groups. SIGNIFICANCE: Our analysis confirms the 2007 US Food and Drug Administration recommendation to screen for HLA-B*1502 allele before starting treatment with carbamazepine in patients of Asian ancestry in the United States.

Cost-utility analysis of competing treatment strategies for drug-resistant epilepsy in children with Tuberous Sclerosis Complex.

BACKGROUND: The management of drug-resistant epilepsy in children with Tuberous Sclerosis Complex (TSC) is challenging because of the multitude of treatment options, wide range of associated costs, and uncertainty of seizure outcomes. The most cost-effective approach for children whose epilepsy has failed to improve with first-line medical therapy is uncertain. METHODS: A review of MEDLINE from 1990 to 2015 was conducted. A cost-utility analysis, from a third-party payer perspective, was performed for children with drug-resistant epilepsy that had failed to improve with 2 antiseizure drugs (ASDs) and that was amenable to resective epilepsy surgery, across a time-horizon of 5years. Four strategies were included: (1) resective epilepsy surgery, (2) vagus nerve stimulator (VNS) implantation, (3) ketogenic diet, and (4) addition of a third ASD (specifically, carbamazepine). The incremental cost per quality-adjusted life year (QALY) gained was analyzed. RESULTS: Given a willingness-to-pay (WTP) of $100,000 per QALY, the addition of a third ASD ($6600 for a gain of 4.14 QALYs) was the most cost-effective treatment strategy. In a secondary analysis, if the child whose epilepsy had failed to improve with 3 ASDs, ketogenic diet, addition of a fourth ASD, and resective epilepsy surgery were incrementally cost-effective treatment strategies. Vagus nerve stimulator implantation was more expensive yet less effective than alternative strategies and should not be prioritized. CONCLUSIONS: The addition of a third ASD is a universally cost-effective treatment option in the management of children with drug-resistant epilepsy that has failed to improve with 2 ASDs. For children whose epilepsy has failed to improve with 3 ASDs, the most cost-effective treatment depends on the health-care resources available reflected by the WTP.

Cost-effectiveness of screening for HLA-A*31:01 prior to initiation of carbamazepine in epilepsy.

OBJECTIVE: Carbamazepine causes severe cutaneous adverse drug reactions that may be predicted by the presence of the HLA-A*31:01 allele in northern European populations. There is uncertainty as to whether routine testing of patients with epilepsy is cost-effective. We conducted an economic evaluation of HLA-A*31:01 testing from the perspective of the National Health Service (NHS) in the United Kingdom. METHODS: A short-term, decision analytic model was developed to estimate the outcomes and costs associated with a policy of routine testing (with lamotrigine prescribed for patients who test positive) versus the current standard of care, which is carbamazepine prescribed without testing. A Markov model was used to estimate total costs and quality-adjusted life-years (QALYs) over a lifetime to account for differences in drug effectiveness and the long-term consequences of adverse drug reactions. RESULTS: Testing reduced the expected rate of cutaneous adverse drug reactions from 780 to 700 per 10,000 patients. The incremental cost-effectiveness ratio for pharmacogenetic testing versus standard care was £12,808 per QALY gained. The probability of testing being cost-effective at a threshold of £20,000 per QALY was 0.80, but the results were sensitive to estimated remission rates for alternative antiepileptic drugs (AEDs). SIGNIFICANCE: Routine testing for HLA-A*31:01 in order to reduce the incidence of cutaneous adverse drug reactions in patients being prescribed carbamazepine for epilepsy is likely to represent a cost-effective use of health care resources.

Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital.

BACKGROUND: Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. METHODS: This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. RESULTS: Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a treatment retention rate of 100%. The effectiveness of AED in terms of reduction of seizure frequency was highest for PHT (100%) and PHB (98%) followed by CBZ (96%) and VPA (95%). PHB and PHT were the cheapest of all AEDs (42 I$ and 56 I$/ year respectively). The costs of VPA and CBZ were two times and LTG and TOP were six to eight times higher. Adverse drug reaction (ADR) were observed among 140 (24.5%) of those with monotherapy. PHT (64%) was the most common drug to cause ADR, CBZ was at the bottom of the list to cause adverse effect (11.6%). VPA and PHB caused weight gain commonly. Adjustment of drug dose or withdrawal due to ADRs was necessary in 39% with PHT and 26% with PHB. CONCLUSION: Though PHT and PHB are cheapest and efficacious among all, CBZ and VPA are less costly, effective and well tolerated drug for seizure control in context of Bangladesh.

Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing.

Human leukocyte antigen B (HLA-B) is a gene that encodes a cell surface protein involved in presenting antigens to the immune system. The variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in response to carbamazepine treatment. We summarize evidence from the published literature supporting this association and provide recommendations for the use of carbamazepine based on HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this article is to provide information to allow the interpretation of clinical HLA-B*15:02 genotype tests so that the results can be used to guide the use of carbamazepine. The guideline provides recommendations for the use of carbamazepine when HLA-B*15:02 genotype results are available. Detailed guidelines regarding the selection of alternative therapies, the use of phenotypic tests, when to conduct genotype testing, and cost-effectiveness analyses are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on the PharmGKB website at (http://www.pharmgkb.org).

Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore.

OBJECTIVE: Asians who carry the HLA-B*1502 allele have an elevated risk of developing Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) when treated with the antiepileptic drugs (AEDs) carbamazepine (CBZ) and phenytoin (PHT). With a focus on Singapore, this analysis identifies circumstances in which genotyping and targeted treatment with alternative AEDs that do not induce SJS/TEN is likely to be more cost-effective than 1) treatment with CBZ or PHT without genotyping or 2) providing a more expensive drug that does not induce SJS/TEN to all patients without genotyping. METHODS: A decision tree model was developed in TreeAge. The model takes into account costs of epilepsy treatments and genotyping, reductions in quality of life and increased costs resulting from SJS/TEN complications, the prevalence of the risk allele, the positive predictive value (PPV) of genotyping, life expectancy, and other factors. RESULTS: Compared with no genotyping and providing CBZ to all, genotyping results in an incremental cost-effectiveness ratio of $37,030/quality-adjusted life year (QALY) for Chinese patients, $7,930/QALY for Malays, and $136,630/QALY for Indians in Singapore. CONCLUSIONS: Because of the different population allele frequencies of HLA-B*1502 among different ethnic groups, genotyping for HLA-B*1502 and providing alternate AEDs to those who test positive is cost-effective for Singaporean Chinese and Malays, but not for Singaporean Indians. Population frequency of HLA-B*1502, PPV, duration of treatment relative to life expectancy, and costs of alternative drugs are the key drivers influencing cost-effectiveness.

Prevalence, utilization, and costs of antiepileptic drugs for epilepsy in Germany--a nationwide population-based study in children and adults.

Nationwide analyses of drug use can provide a prevalence estimate of the underlying disease and can help in understanding the characteristics of treatment. This study aimed for such analyses regarding the utilization of antiepileptic drugs (AED) for epilepsy in Germany. In 2009, all 4,115,705 AED prescriptions of all German patients with statutory health insurance (70,011,508 persons) were retrospectively analyzed. The IMS(®) LRx database served as data source, which accesses nationwide pharmacy data centers processing all German prescription data. To establish the age and sex-specific percentage of patients taking AED because of epilepsy, we used a second database, Disease Analyzer(®), which covered a representative sample of the German population (7.2 million patients) and contained ICD10 codes alongside with prescription data. The period prevalence of patients taking AED because of epilepsy was 9.1/1,000 (children/adolescents: 5.2/1,000; elderly: 12.5/1,000). Of the patients, 83.1 % took at least one of four AED: valproate (29.8 %), carbamazepine (26.4 %), lamotrigine (21.4 %), and levetiracetam (16.9 %). Oxcarbazepine and sultiame were popular with pediatricians. Elderly patients frequently received phenytoin and primidone. More than half of the patients were treated by family physicians; 68 % took AED in monotherapy and 7.9 % received >2 AED (children/adolescents: 12.5 %). The costs for AED prescribed for epilepsy amounted to €285.1 Mio (median AED costs/patient: €158/a). The German 2009 prevalence of epileptic patients taking AED was 9.1/1,000. Family physicians cared for the majority of patients. Prevalence and prescribing patterns changed with age. Costs of AED against epilepsy added up to 1 % of total medication costs in Germany.

Economic evaluation of anti-epileptic drug therapies with specific focus on teratogenic outcomes.

BACKGROUND: Anti-epileptic drugs are known to be teratogenic, yet many women do need to continue the anti-epileptic drug use during pregnancy. OBJECTIVES: To perform an economic evaluation of the anti-epileptic drug choice in young women who potentially wish to become pregnant. In particular, to estimate the impact of teratogenicity on the costs per quality adjusted life year (QALY). METHODS: A decision-tree model is used to calculate the costs per QALY, taking into account the malformation risk in offspring due to the exposure to carbamazepine, lamotrigine or valproic acid, based on the European birth cohort of 2007. Probabilistic sensitivity analyses were performed using Monte Carlo simulation. RESULTS: Valproic acid is dominated by carbamazepine after rank ordering on costs. The incremental cost-effectiveness of lamotrigine vs carbamazepine was estimated at €175,534 per QALY. Although valproic acid was dominated by carbamazepine in terms of costs and related effects, it is clinically relevant to compare lamotrigine with valproic acid. In particular, treatment options are dependent on several individual and clinical characteristics and these agents are therefore not always considered as interchangeable for all specified populations. The incremental cost-effectiveness for lamotrigine vs valproic acid was estimated at €13,370 per QALY. With assuming a willingness to pay threshold of €50,000 per QALY, results from the probabilistic analysis resulted in an acceptance level for lamotrigine vs carbamazepine and lamotrigine vs valproic acid of 4% and 99%, respectively. CONCLUSION: Based on epidemiological data it is advised to whenever possible avoid valproic acid during pregnancy. Both carbamazepine and lamotrigine are estimated to be cost-effective treatment options vs valproic acid if focused on teratogenicity.

Randomised controlled study-efficacy of clonidine versus carbamazepine in children with ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorder with a prevalence of 8-12%. Even though psychostimulants remain the treatment of choice, its cost and availability in developing countries limits the usage of the drug. In view of free availability and low cost, a Randomized controlled study was carried out using two second line drugs (clonidine and carbamazepine) in a tertiary care hospital, Pondicherry, South India. OBJECTIVE: To compare the efficacy of clonidine and carbamazepine in children with ADHD. METHOD: With approval of ethics committee, a prospective, Double-blind, Randomized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD (age group 4-12 years), over a period of 2 years (2005-07) in a tertiary care hospital, Pondicherry, South India. RESULTS: Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine. Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions. CONCLUSION: Clonidine can be a safer and cheaper alternative in treatment of children with ADHD, with a predominant effect on their hyperactivity and impulsivity symptoms.

The effect of adjunctive mood stabilizers on antipsychotic utilization pattern and health resource utilization for Medicaid enrollees with schizophrenia.

BACKGROUND: Prescribing adjunctive mood stabilizers to manage schizophrenia is prevalent, despite the lack of substantial evidence to support the long-term use of this treatment regimen. OBJECTIVE: The objective of this study was to assess the impact of using adjunctive mood stabilizers on antipsychotic utilization, total health expenditures, inpatient hospitalizations, long-term care stays, and emergency room (ER) visits for patients with schizophrenia. METHODS: Georgia Medicaid claims from 1999 through 2001 were analyzed to identify recipients diagnosed with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 295. XX). The treatment groups consisted of subjects who received combination therapy of mood stabilizers and antipsychotics (including both atypical and typical medications), while the comparison group consisted of subjects who were on antipsychotic medications without exposure to the mood stabilizers under investigation. Four treatment groups (valproate, lithium, carbamazepine, and combination mood stabilizer therapy) were formed based on the mood stabilizers patient received. Differences in annual health care use and expenditures were estimated between propensity score matched treatment and comparison groups controlling for comorbidity, prior utilization, demographic, and health provider specialty. RESULTS: During the 1-year observation period, subjects in treatment groups filled an average of 200-days supply of adjunctive mood stabilizers. These adjunctive mood stabilizer recipients had significantly longer antipsychotic treatment durations than the subjects who did not have exposure to mood stabilizers (valproate + antipsychotic vs. antipsychotic only, net difference: 56.47 days, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: 90.25 days, p < 0.0001; carbamazepine + antipsychotic vs. antipsychotic only, net difference: 41.27 days, p = 0.0439; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net difference: 83.14 days, p < 0.0001). The intensive pharmacotherapy associated with treatment groups resulted in $900-$1300 higher pharmacy costs than the comparison groups (valproate + antipsychotic vs. antipsychotic only, net difference: $1218.43, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: $985.79, p = 0.0015; carbamazepine + antipsychotic vs. antipsychotic only, net difference: $911.63, p = 0.0497; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net difference: $1281.91, p < 0.0047). However, there were no statistically significant differences for total health expenditures, hospitalizations, emergency room visits, and nursing home admissions between propensity-matched treatment and control groups. CONCLUSIONS: There were no differences in health care costs or utilization of ER, long-term care, and inpatient services between schizophrenia patients who did and did not receive adjunctive mood stabilizer; however, longer antipsychotic treatment durations were observed in patients receiving adjunctive mood stabilizers. Interpretation of these results is limited by the unknown selection bias between the treatment and the comparison groups and the relatively small number of patients in some treatment groups. The development of a better-controlled study to further evaluate this treatment regimen is warranted.

A cost-effectiveness decision model for antiepileptic drug treatment in newly diagnosed epilepsy patients.

OBJECTIVE: To establish cost-effectiveness of antiepileptic drug (AED) treatment strategies of newly diagnosed patients with epilepsy. METHODS: A decision analysis was carried out comparing effectiveness and treatment cost of six treatment strategies comprising carbamazepine (CBZ), lamotrigine (LTG), and valproate (VPA) as first-line and second-line drugs. Three outcome groups were defined: complete success, partial success, and failure. Data on seizure control and failure due to adverse effects were derived from the literature. Data on resource use and costs were collected for each outcome group by means of a patient survey. RESULTS: Cost data were obtained from 71 patients. Cost increased from complete success to failure outcome groups. The probability of obtaining complete success varied from 64% (VPA-CBZ strategy) to 74% (LTG-VPA strategy). The strategy LTG-VPA was more effective than the least expensive strategy CBZ-VPA, but at higher costs per additional effectively treated patient. Probabilistic sensitivity analysis confirmed these findings to be robust. Subsequent analysis showed that changing inclusion criteria used in the selection of the studies from the literature had a major effect on cost-effectiveness ratios of the various strategies. The probability that LTG first-line therapy is the most cost-effective option remains small, even defining a high cost-effectiveness threshold. Nevertheless, LTG second-line strategies can be cost-effective depending on the willingness to pay for patient improvement. CONCLUSIONS: Only a few studies satisfied our inclusion criteria for employment in our decision model. Our model supports the use of conventional AEDs as first-line options for patients with newly diagnosed epilepsy. LTG second-line therapy is likely to be the most cost-effective option in case society is willing to pay more than Euro 6000 for an additional successfully treated patient. This study also illustrates that, with the data presently available, the outcome of decision analysis for AED treatment choice depends on the inclusion criteria used to select trials. Prospective real-life studies are needed in which first- and second-line treatment strategies are compared with respect to both effectiveness and costs.

Choosing a first drug treatment for epilepsy after SANAD: randomized controlled trials, systematic reviews, guidelines and treating patients.

The ILAE treatment guidelines for initial monotherapy emphasise the poor quality of information available to inform everyday clinical practice. Industry sponsored studies comparing antiepileptic drugs answer restricted licensing questions, rather than those relevant to the clinical community (patients, health professionals and founders of health care). The SANAD study, a pragmatic randomized clinical trial, offers a methodology to address some of these questions. It identifies lamotrigine as a cost-effective alternative to carbamazepine for the treatment of focal epilepsies, but confirms valproate as the most effective drug for the treatment of generalized or unclassified epilepsy.

Economic evaluation of oral treatments for neuropathic pain.

UNLABELLED: The effectiveness of amitriptyline, carbamazepine, gabapentin, and tramadol for the treatment of neuropathic pain has been demonstrated, but it is unknown which one is the most cost-effective. We designed a cost-utility analysis of a hypothetical cohort with neuropathic pain of postherpetic or diabetic origin. The perspective of the economic evaluation was that of a third-party payor. For effectiveness and safety estimates, we performed a systematic review of the literature. For direct cost estimates, we used average wholesale prices, and the American Medicare and Clinical Laboratory Fee Schedules. For utilities of health states, we used the Health Utilities Index. We modeled 1 month of therapy. For comparisons among treatments, we estimated incremental cost per utility gained. To allow for uncertainty from variations in drug effectiveness, safety, and amount of medication needed, we conducted a probabilistic Monte Carlo simulation. Amitriptyline was the cheapest strategy, followed by carbamazepine, and both were equally beneficial. Gabapentin was the most expensive as well as the least beneficial. A multivariable probabilistic simulation produced similar results to the base-case scenario. In summary, amitriptyline and carbamazepine are more cost-effective than tramadol and gabapentin and should be considered as first-line treatment for neuropathic pain in patients free of renal or cardiovascular disease. PERSPECTIVE: Prescription practices should be based on the best available evidence, which includes the evaluation of the medication's cost-effectiveness. This does not mean that the cheapest or the most expensive, but rather the most cost-effective medication should be chosen-the one whose benefits are worth the harms and costs. We report a cost-effectiveness evaluation of treatments for neuropathic pain.

A pharmacoeconomic comparison of monotherapy with Tegretol, Finlepsin and Trileptal (preliminary data).

AIM: Pharmacoeconomics comprises a system of relatively new methods that inform policy makers about the costs and benefits of different therapies so that limited health care resources may be allocated efficiently. The purpose of this study was to perform a pharmacoeconomic comparison of three of the most widely used antiepileptic drugs in Bulgaria: carbamazepine (two different products: Tegretol and Finlepsin) and oxcarbazepine (Trileptal). PATIENTS AND METHODS: The inclusion criteria for entering the study were: women or men of age with newly detected and clinically diagnosed epilepsy,monotherapy treatment with the studied drugs, ability to keep personal records. The follow-up visits were conducted in three-month periods, each visit including a thorough evaluation of effectiveness, costs and quality of life. Effectiveness was assessed as seizure reduction percentage and time till new seizure. Costs included direct and indirect medical and nonmedical costs, related to epilepsy or its treatment. The quality of life of the patient was assessed with Quality of Life in Epilepsy Inventory 31 (QOLIE)--an evaluation instrument accepted for use in clinical practice. The statistical methods used included: descriptive analysis, Pearson correlation and Kaplan-Meyer analyses. RESULTS: The mean seizure reduction was 86.05% for Finlepsin, 83.31% for Tegretol and 66.67% for Trileptal. There were no seizure-free patients on Trileptal, while almost 60% of Tegretol and nearly 50% in Finlepsin patients remained seizure-free for a period of one year. CONCLUSIONS: The quality of life of all patients was high, indicating good efficacy and safety as assessed by patients. There was a significant difference in terms of costs in the Trileptal group compared with the other two groups --it incurred higher annual costs as well as higher cost-per-QALY value.

A cost comparison of alternative regimens for treatment-refractory partial seizure disorder: an econometric analysis.

BACKGROUND: Partial seizure disorder is typically treated by monotherapy with antiepileptic drugs (AEDs). However, when the condition is refractory to the initial treatment regimen, patients may be switched to monotherapy with another AED or to combination therapy with the initial AED plus a second AED. OBJECTIVES: The purpose of this study was to examine the economic costs associated with treatment-refractory partial seizure disorder and to compare the costs of 2 alternative approaches: a switch to oxcarbazepine (OXC) monotherapy or the addition to the regimen of another AED (AED add-on). METHODS: Adult patients with a diagnosis of partial seizure disorder who received initial AED monotherapy between January 1, 2000, and March 31, 2003, were identified from the PharMetrics Patient-Centric Database, a health plan administrative claims database. The medical and pharmacy history of these patients was analyzed from 6 months before a change to either OXC monotherapy or AED add-on therapy through 12 months after the change in treatment. Total health care resource utilization and the associated costs were compared within each cohort before and after the change, as well as between cohorts, with statistical differences tested using Wilcoxon rank sum tests. Multivariate econometric analyses were performed to examine the impact of age, sex, geographic location, Charlson Comorbidity Index, and the presence of specific comorbidities. RESULTS: Demographic and clinical characteristics 102 were similar between the OXC monotherapy cohort (n = 259) and the AED add-on cohort (n = 795). Annual direct treatment costs increased in both groups in the period after the failure of initial monotherapy, increasing from 10,462 US dollars to 11,360 US dollars in the OXC cohort and from 10,137 US dollars to 12,201 US dollars in the AED add on cohort (P < 0.01). Increased pharmacy costs were the primary driver behind cost increases in both cohorts. Patients in the AED add-on cohort were significantly more likely to have an emergency department visit during the period after the failure of initial monotherapy compared with the OXC monotherapy cohort (odds ratio = 1.52; P < 0.05). CONCLUSION: Despite limitations, the results of retrospective analysis of claims data suggest that the care of patients with treatment-refractory partial seizure disorder is costly and may vary significantly based on the pattern of care.

The use of lamotrigine and other antiepileptic drugs in paediatric patients at a Malaysian hospital.

OBJECTIVE: (1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs). METHOD: A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang. MAIN OUTCOME MEASURE: Seizure frequency, cost of drug and types of AED prescribed. RESULTS: A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00). CONCLUSION: The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

Patterns of care, outcomes, and direct health plan costs of antiepileptic therapy: a pharmacoeconomic analysis of the available carbamazepine formulations.

BACKGROUND: Although generic formulations of immediate-release carbamazepine (IR-CBZ) are available, extended-release delivery systems may offer important advantages, including the convenience of less-frequent administration and smaller peak-to-trough serum carbamazepine (CBZ) fluctuations. OBJECTIVE: The aim of this study was to compare the patterns of pharmacotherapy, rates of adverse events, and the utilization costs among patients treated with the available CBZ formulations (ie, generic and branded IR-CBZ, and extended-release CBZ (ER-CBZ) capsules [Carbatrol, Shire US Inc., Wayne, Pennsylvania] and tablets [Tegretol-XR, Novartis Pharmaccuticals Corporation, East Hanover, New Jersey]). METHODS: Data were retrieved from the PharMetrics patient-centric database (which contains integrated claims data for almost 36 million unique patients from 61 US health plans) for patients who were diagnosed with epilepsy and initiated CBZ between July 1999 and June 2001. Patient demographic and clinical characteristics, adverse events, discontinuations, CBZ therapy switches, and utilization and costs for related care subsequent to treatment initiation were recorded. Annual rates of adverse events and discontinuations were calculated, and the risks of these events were compared across treatment groups. RESULTS: Data were gathered for 1737 patients. The branded CBZ group was demographically and clinically different than the other groups (ie, migraine and cerebral palsy prevalence) and therefore was excluded from event-risk analyses. Results of the proportional hazards regression analysis indicated that Tegretol-XR patients were more likely to experience common central nervous system (CNS)-related adverse events relative to Carbatrol (hazard ratio, 1.67; P = 0.043). A lower percentage of subjects switched off ER-CBZ relative to IR-CBZ (Carbatrol, 5.2%; Tegretol-XR, 5.7%; generic IR-CBZ, 13.0%; branded IR-CBZ, 16.7%). Differences in mean payments for epilepsy-related health care services at 1 year among Carbatrol, Tegretol-XR, and branded or generic CBZ did not reach statistical significance. CONCLUSIONS: Among the available CBZ formulations, Carbatrol was associated with a lower incidence of common CNS adverse events. ER-CBZ formulations were also associated with reduced likelihood of therapy discontinuation or switching CBZ medications, relative to patients taking generic IR-CBZ, in this retrospective data analysis.

Effectiveness and medical costs of divalproex versus lithium in the treatment of bipolar disorder: results of a naturalistic clinical trial.

OBJECTIVE: The clinical, quality of life (QOL), and medical cost outcomes of treatment with divalproex were compared with lithium in patients with bipolar I disorder over 1 year. METHODS: In a pragmatic, randomized clinical trial, 201 adults hospitalized with bipolar I manic or mixed episodes were randomized to divalproex or lithium, in addition to usual psychiatric care, and followed for 1 year. All subsequent treatment of bipolar disorder was managed by the patient's psychiatrist. Symptoms of mania and depression were evaluated at baseline and at hospital discharge. Assessments at the start of maintenance therapy and after 1, 3, 6, 9 and 12 months included manic and depressive symptoms, disability days and QOL. Medical resource use data were also collected monthly and costs were estimated using national sources. RESULTS: Divalproex-treated patients (12%) were less likely to discontinue study medications for lack of efficacy or adverse effects than lithium-treated patients (23%). No statistically significant differences between the treatment groups were observed over the 1-year maintenance phase for clinical symptoms, QOL outcomes, or disability days. Mean estimated total medical costs were USD 28,911 for the divalproex group compared with USD 30,666 for the lithium treatment group. Patients continuing mood stabilizer therapy at 3 months had slightly better health outcomes and substantially lower total medical costs than those who discontinued therapy ( USD 10,091 versus USD 34,432, respectively). CONCLUSIONS: Divalproex maintenance treatment for bipolar disorder resulted in comparable medical costs, clinical and QOL outcomes compared with lithium. Patients remaining on mood stabilizer therapy had substantially lower total medical costs and better health outcomes compared with those who discontinued therapy.