Gamma-aminobutyric Acid Enriched Rice Bran Diet Attenuates Insulin Resistance and Balances Energy Expenditure via Modification of Gut Microbiota and Short-Chain Fatty Acids.

In this study, gamma-aminobutyric acid (GABA) enriched rice bran (ERB) was supplemented to obese rats to investigate the attenuation of metabolic syndromes induced by high-fat diet. ERB-containing diet stimulated butyrate and propionate production by promoting Anaerostipes, Anaerostipes sp., and associated synthesizing enzymes. This altered short-chain fatty acid (SCFA) distribution further enhanced circulatory levels of leptin and glucagon-like peptide-1, controlling food intake by downregulating orexigenic factors. Together with the enhanced fatty acid ß-oxidation highlighted by Prkaa2, Ppara, and Scd1 expression via AMPK signaling pathway and nonalcoholic fatty liver disease pathway, energy expenditure was positively modulated. Serum lipid compositions showed ERB supplement exhibited a more efficient effect on lowering serum sphingolipids, which was closely associated with the status of insulin resistance. Consistently, genes of Ppp2r3b and Prkcg, involved in the function of ceramides in blocking insulin action, were also downregulated following ERB intervention. Enriched GABA and phenolic acids were supposed to be responsible for the health-beneficial effects.

Policies to mitigate nonmedical use of prescription medications: how should emerging evidence of gabapentin misuse be addressed?

INTRODUCTION: Over the past decade, increased prescription supply has facilitated an epidemic of nonmedical use of controlled substances, including predominantly opioids, as well as benzodiazepines, z-hypnotics, and stimulants. Areas covered: More recently, misuse of noncontrolled prescriptions, such as gabapentin, has been detected. Gabapentin misuse has been associated with drug-related harm and increased healthcare service utilization in a few studies, including a recent large-sample analysis of commercially insured enrollees in the United States (U.S.) Responding to this emerging base of evidence, a small number of U.S. states have acted to prevent or detect gabapentin misuse by requiring the inclusion of gabapentin utilization in reporting to local Prescription Drug Monitoring Programs (PDMPs) and/or imposing other restrictions on gabapentin prescribing (e.g., classification as a controlled substance, quantity limits). These efforts may result in unintentional harm by (1) encouraging 'doctor shopping' across state lines to seek lenient regulatory policies and (2) placing the burden for mitigating misuse on individual practitioners. Expert opinion: We call for a unified national approach, comprising federal regulation and enhanced PDMP reporting to address gabapentin misuse, while laying the groundwork for management of new medications of abuse that the healthcare industry may encounter in the future.

An economic method to build a puffing instrument for drug application in vitro.

BACKGROUND: In in vitro electrophysiological studies, a quick application of picoliters of drug within milliseconds is required to avoid the desensitization of membrane receptors. However, conventional gravity-fed drug delivery devices sometime fail to achieve this. Moreover, the high financial cost of the advanced drug delivery system often limits the application of commercial instruments in academic research. NEW METHOD: Taking advantage of the availability of data acquisition system and software in almost every electrophysiology laboratory, a simple puffing device was designed and assembled using low-cost commercially off-the-shelf components to inject picoliter amounts of drugs. RESULTS: An optimal drug delivery with precise timing and volume was achieved using the custom made puffing device. The glutamate-evoked currents of cortical neurons recorded with patch-clamp technique were maintained for a prolonged period of time. Similarly, puffed inhibitory transmitters including GABA and glycine also produced satisfactory currents. COMPARISON WITH EXISTING METHOD(S): Our custom-made puffing system holds the advantage over conventional gravity-fed systems in operating within milliseconds of time. The channel number of the new device can easily be increased by simply adding more identical modules in parallel, and thus offering more flexibility than commercial puffing devices. CONCLUSIONS: This custom-made puffing device can be characterized as reliable, modular and inexpensive system for modern drug delivery research and application.

Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action.

IMPORTANCE: To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure. OBJECTIVE: To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS: Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES: Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations. RESULTS: Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE: The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes.

Impact of a pregabalin step therapy policy among medicare advantage beneficiaries.

BACKGROUND: Managed healthcare organizations often utilize formulary management strategies such as prior authorization and step therapy to guide appropriate medication use and to control medication expenditures. The objective of this study was to examine clinical and economic outcomes associated with implementation of a pregabalin step therapy (ST) policy among Medicare Advantage Prescription Drug (MAPD) members. METHODS: Pharmacy and medical claims data from Humana (restricted cohort; ST policy implemented 01/01/2009) and Thomson Reuters MarketScan(®) (unrestricted cohort) were analyzed for MAPD members aged 65 to 89 years receiving treatment for painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN) or fibromyalgia (FM). Difference-in-differences (DID) was used to examine year-over-year changes in disease-related and all-cause utilization and costs. Regression analyses examined medication utilization and healthcare expenditures after controlling for between-group compositional differences. RESULTS: We identified 13,911 members in the restricted cohort and matched to members from unrestricted health plans. FM (51.0%) and pDPN (41.8%) were the most common diagnoses. Members in the unrestricted cohort were older and had a greater level of comorbidity than members in the restricted cohort. The restricted cohort demonstrated greater year-over-year decrease in pregabalin utilization and increase in year-over-year gabapentin utilization compared with the unrestricted cohort. ST restriction was associated with an increase in disease-related pharmacy costs and a decrease in total medical costs for the restricted cohort compared with the unrestricted cohort. There was no difference between cohorts in total healthcare cost. CONCLUSION: After controlling for differences in age and comorbidity burden between the groups, implementation of a pregabalin ST restriction was associated with increased disease-related pharmacy costs and decreased total medical costs; however, there was no net difference in total healthcare cost or total pharmacy cost.

Efectividad y seguridad de gabapentina y pregabalina como monoterapia de primera línea en adultos con dolor neuropático / Effectiveness and safety of gabapentin and pregabalin as first-line monotherapy in adults with neuropathic pain

Antecedentes: Descripción de la condición de salud de interés: La Asociación Internacional del Estudio del Dolor en el año 2011 definió el dolor neuropático como una afección neurológica crónica causado por una lesión o enfermedad del sistema nervioso. Se debe a una lesión o mal funcionamiento del sistema nervioso, a un daño del nervio en sí (u otra parte del sistema sensorial) y no a una activación anormal de las vías nociceptoras. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. Descripción de las tecnologías: Gabapentina y pregabalina son medicamentos anticonvulsivantes empleados en el tratamiento del dolor neuropático; a ctúan disminuyendo la liberación de neurotransmisores excitadores, lo que reduce la entrada de calcio en las terminaciones nerviosas. Las dos tecnologías tienen registro sanitario INVIMA para la indicación de interés. Evaluación de efectividad y seguridad: Pregunta de evaluación: En adultos con dolor neuropático, ¿cuál es la efectividad y seguridad de gabapentina y pregabalina comparadas con amitriptilina, oxcarbazepina, duloxetina, tramadol (sólo o en combinaciones) o lidocaína en parches, como monoterapia de primera línea para el alivio del dolor? La pregunta de evaluación fue refinada y validada con base en: autorización de mercadeo de \r\nlas tecnologías para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (clasificación ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías y revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), \r\nestudios de carga de enfermedad y consulta con un experto temático (especialista clínico). No se dentificaron otros comparadores relevantes para la evaluación. Población: Adultos con dolor neuropático tipo: Neuropatía diabética periférica; Neuralgia posherpética; Dolor neuropático asociado con lesión de la médula espinal. \r\nLa población se refinó después de revisar la evidencia disponible, considerando además, que los efectos de las tecnologías bajo evaluación podrían diferir entre pacientes con distintos tipos de dolor neuropático. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: En pacientes con neuropatía diabética periférica, gabapentina es una opción con ventajas en efectividad, sin ventajas en seguridad y tolerabilidad. En la misma población, pregabalina sin discriminar por dosis no tiene ventajas en efectividad; en dosis ≥ 300 mg es una opción con ventajas en efectividad, no es segura y no presenta ventajas en tolerabilidad; para dosis ≤ 150 mg la evidencia sobre su efectividad no es concluyente, no presenta ventajas en cuanto a seguridad y tolerabilidad. En pacientes con neuralgia posherpética, la evidencia sobre la efectividad de gabapentina no es concluyente, para el mismo tipo de dolor, pregabalina es una opción desfavorable en términos de efectividad y de seguridad a altas dosis. En pacientes con dolor neuropático asociado con lesión de la médula espinal no se identificó evidencia sobre la efectividad de gabapentina o pregabalina. En la misma población, gabapentina no tiene ventajas en tolerabilidad, por su parte, pregabalina no es segura y no presenta ventajas en tolerabilidad. La calidad de la evidencia para las comparaciones de interés y desenlaces descritos es alta.

Adding pregabalin or gabapentin for the management of community-treated patients with painful diabetic peripheral neuropathy: a comparative cost analysis.

BACKGROUND AND OBJECTIVE: Painful diabetic peripheral neuropathy (pDPN) is a highly prevalent complication of diabetes mellitus, which is associated with substantial costs to society and national health systems. This economic impact varies depending on the therapeutic management provided to patients. The objective of this study was to compare healthcare resource utilization and costs among pDPN patients newly treated with pregabalin or gabapentin in routine medical practice. METHODS: We performed a retrospective medical records study of pDPN patients newly treated with pregabalin or gabapentin as an add-on therapy who are covered by the Badalona Serveis Assistencials (BSA) health plan, a healthcare provider in Spain, from 2006 to 2009. Healthcare resource utilization and days off work were assessed. The societal perspective was used to estimate costs. RESULTS: Three hundred and ninety-five records were eligible for analysis: 227 (57.5%) included pregabalin and 168 (42.5%) gabapentin. Mean (standard deviation) concomitant use of analgesics throughout the study was higher in the gabapentin cohort [3.9 (2.2) vs. 3.1 (2.1); p < 0.05], mainly due to greater use of non-narcotics (78.0 vs. 71.8%; p < 0.05) and opioids (32.7 vs. 28.6%; p < 0.05). Healthcare costs accounted for 59.2% of total costs, of which 71.9% occurred in primary care, with a mean cost per patient of €2,476 (year 2010 values). Adjusted mean (95% CI) total costs were significantly lower in pregabalin-treated patients [€2,003 (1,427-2,579)] than in gabapentin-treated patients [€3,127 (2,463-3,790)] (p = 0.013), mainly due to lower healthcare costs [€1,312 (1,192-1,432) vs. €1,675 (1,537-1,814); p < 0.001]. CONCLUSIONS: Adding pregabalin to existing pDPN therapy resulted in lower total healthcare costs and lower resource utilization than resulted from adding gabapentin.

Assessment of the antinociceptive effects of pregabalin alone or in combination with morphine during acetic acid-induced writhing in mice.

Visceral pain currently represents one of the most important pain treatment challenges in clinical practice, and investigators across the world are continuously designing and conducting numerous studies in search of new analgesics and new combination therapies. The current study assessed the analgesic effects of saline, pregabalin (2, 5, 17, 50, 100, and 200 mg/kg, i.p.) and morphine (0.25, 0.5, 1, 3 and 5 mg/kg) alone or in combination on acetic-acid induced abdominal contractions in mice. The number of writhes and the inhibitory effects (as percentages, %E) were calculated as antinociception indexes. These indexes indicated that both pregabalin (Prg) and morphine (Mrp) produced dose-dependent antinociception. Pregabalin at 5 mg/kg (%E=32.5±4.0) or 2 mg/kg (%E=20.8±4.5) and morphine at 0.25 mg/kg (%E=20.2±7.8) and 0.5 mg/kg (%E=43.6±4.5) exhibited antinociceptive effects, and the combination of pregabalin and morphine produced significantly greater antinociceptive effects (%E=62.4±5.8 for Prg5+Mrp0.25; %E=71.7±4.8 for Prg5+Mrp0.5; and %E=54.1±4.0 for Prg2+Mrp0.25), although this enhancement was not observed when morphine was combined with 17 mg/kg pregabalin. Pre-treatment with 2 mg/kg (i.p.) naloxone did not affect increased analgesia when combined with these drugs. A dose-response curve was established for pregabalin at a fixed morphine dose and revealed that, at low doses, pregabalin dose-dependently enhanced the antinociceptive effects, while the opposite was true at high doses (17 and 25 mg/kg). In conclusion, pregabalin can produce levels of antinociception that are similar to those of morphine in acetic acid-induced viscero-somatic pain. The enhancement of antinociception produced by the co-administration of morphine and pregabalin is termed a supra-additive interaction and occurred at low doses but not at high doses. These findings militate for increased attention and caution in clinical settings.

Cost-utility of pregabalin as add-on to usual care versus usual care alone in the management of peripheral neuropathic pain in Belgium.

BACKGROUND AND OBJECTIVES: The cost effectiveness of pregabalin as an add-on to the standard treatment of Belgian patients with post-herpetic neuralgia (PHN) had been demonstrated in a previously published Markov model. The purpose of this study was to update that model with more recent cost data and clinical evidence, and reevaluate the cost effectiveness from the payer's perspective of add-on pregabalin in a wider set of NeP conditions. METHODS: The model, featuring 4-week cycles and a 1-year time horizon, consisted in four possible health states: mild, moderate or severe pain and withdrawn from therapy. Three versions of the model were developed, using transition probabilities derived from pain scores reported in three placebo-controlled studies. The two treatment arms were 'usual care' or 'usual care + pregabalin'. Resource use and utility data were obtained from a chart review and unit costs from recent published data. The final outcome of the model was the incremental cost per quality-adjusted life-year (QALY) gained when adding pregabalin to standard care. RESULTS: Based on 1000 simulations, two versions of the model showed that pregabalin was dominant respectively in 94.8% and 67.2% of the simulations, while the incremental cost per QALY was below €32,000/QALY in respectively 99.1% and 94.6% of the simulations. The third version did not show cost effectiveness, despite an incremental cost of only €300 after 1 year. However, in the corresponding study, patients seemed less responsive to GABA analogs, since 55% of them had failed to respond to gabapentin before study inclusion. LIMITATIONS: The studies upon which the model is based have a short follow-up time as compared to the model horizon. The endpoints of two studies were only provided at the aggregated level and do not necessarily reflect the real practice. CONCLUSION: Based on this analysis, it can be concluded that from a Belgium payer perspective pregabalin offers a slight increase in quality of life in the studied populations as compared to standard care. Pregabalin is cost effective in the majority of cases except in one published clinical study, despite a low incremental cost per year (€300).

[Potentially addictive drugs on reimbursable prescription for chronic severe pain]. / Potensielt vanedannende legemidler på blåresept ved kroniske sterke smerter.

BACKGROUND: Changes in the Norwegian drug reimbursement system in 2008 included the establishment of a new reimbursement code (-71) which authorises coverage of expenditures for potentially addictive drugs in patients with severe, predominantly non-malignant, chronic pain. This reform has hitherto not been evaluated. MATERIAL AND METHOD: We assessed national data on drug reimbursements in accordance with code -71 for the period 2008-2011, and anonymised copies of all confirmation letters granting reimbursements according to code -71 in Central Norway (three counties) for 2010. Approximately 1300 individual applicants' gender and age, diagnosis, potentially addictive drug applied for, drug dose, and identity and specialty of the prescribing physician, were recorded. RESULTS: From the time of establishment, reimbursement code -71 has been utilised by an increasing number of individuals, encompassing close to 10,000 subjects in 3rd quarter 2011. Almost one-third of the approved applications were for pregabalin, and the rest were for various opioids. The diagnoses were most often derived from the musculoskeletal and nervous systems, and were often nonspecific. A considerable number of treatment regimens were not in accordance with current principles for the management of chronic non-malignant pain, and drug doses were at times remarkably high. INTERPRETATION: Aspects of this drug reimbursement regulation should be closely monitored, and may be in need of changes.

Real-world treatment of post-herpetic neuralgia with gabapentin or pregabalin.

BACKGROUND AND OBJECTIVES: There are limited data examining the real-world use of gabapentin and pregabalin for the treatment of post-herpetic neuralgia (PHN). This study examines dosing patterns, therapy outcomes, healthcare utilization and costs of patients with PHN who initiate treatment with gabapentin or pregabalin. METHODS: This was a retrospective administrative claims data analysis from July 2005 to February 2010. Patients with PHN initiating gabapentin or pregabalin (index therapy) from January 2006 to February 2009 were identified and were observed for 12 months after index therapy initiation. Outcomes were mean daily dosages of the index therapy, attainment of minimally effective dosages of gabapentin (≥ 1,800 mg/day) or pregabalin (≥ 150 and ≥ 300 mg/day) persistence, discontinuation, index therapy switching, addition of neuropathic pain medications to index therapy, and healthcare resource use and costs. RESULTS: 1,645 patients were identified. The mean daily dosage was 826 mg for gabapentin and 187 mg for pregabalin. Only 52.6 % of patients initiating gabapentin and 56.9 % initiating pregabalin obtained a refill during the post-index period. Approximately 14 % of patients treated with gabapentin reached the target dosage (1,800 mg/day). For pregabalin, 87 % reached ≥ 150 mg/day and 27 % reached ≥ 300 mg/day. On average, patients took 10 weeks to reach 1,800 mg/day gabapentin, and 5.0 and 9.2 weeks to reach ≥ 150 mg/day and ≥ 300 mg/day pregabalin, respectively. Approximately one-third of patients in both index therapy cohorts added a pain medication; more than half added opioids. The percentage of patients switching from either drug (57 %) or adding a therapy (34 %) were similar between index therapy cohorts; opioids were the most common therapy patients switched to or added. CONCLUSION: It appears that gabapentin and pregabalin are not used effectively to treat PHN. Suboptimal dosing and discontinuation may be associated with supplementary use of other analgesics, especially opioids.

A cost-utility analysis of pregabalin versus duloxetine for the treatment of painful diabetic neuropathy.

The objective of the current study was to determine the cost-utility of pregabalin versus duloxetine for treating painful diabetic neuropathy (PDN) using a decision tree analysis. Literature searches identified clinical trials and real-world studies reporting the efficacy, tolerability, safety, adherence, opioid usage, health care utilization, and costs of pregabalin and duloxetine. The proportions of patients reported in the included studies were used to determine probabilities in the decision tree model. The base-case model included the Food and Drug Administration (FDA)-approved doses of pregabalin (300 mg/day) and duloxetine (60 mg/day), whereas "real-world" sensitivity analyses explored the effects over a range of doses (pregabalin 75-600 mg/day, duloxetine 20-120 mg/day). A 6-month time horizon and a US third-party payer perspective were chosen for the study. Outcomes from the model were expressed as cost per quality-adjusted life-year (QALY). In the base-case model, duloxetine cost less and was more effective than pregabalin (incremental cost -$187, incremental effectiveness 0.011 QALYs). Results from two real-world sensitivity analyses indicated that duloxetine cost $16,300 and $20,667 more per additional QALY than pregabalin. Using a decision tree model that incorporated both clinical trial and real-world data, duloxetine was a more cost-effective option than pregabalin in the treatment of PDN from the perspective of third-party payers.

The cost-effectiveness of pregabalin in the treatment of fibromyalgia: US perspective.

OBJECTIVE: To evaluate the cost-effectiveness of pregabalin in the treatment of fibromyalgia in a US patient population. METHODS: A decision-analytic model was developed comparing pregabalin 150 mg twice a day (BID) and pregabalin 225 mg BID to placebo, duloxetine, gabapentin, tramadol, milnacipran, and amitriptyline in patients with severe fibromyalgia (Fibromyalgia Impact Questionnaire score >59; pain score >6.5). The model estimated response rates for all treatments at 12 weeks based on three randomized trials with pregabalin and a systematic review of published randomized controlled trials. Response was categorized as ≥30% improvement in baseline pain score plus global impression of change rating of much improved or very much improved. After 12 weeks of treatment, responders to treatment entered a treatment Markov model in which response was maintained, lost, or treatment discontinued. The cost-effectiveness end-points were cost per responder at 12 weeks and 1 year. Resource use was estimated from published studies and costs were estimated from the societal perspective. RESULTS: Over 12 weeks, total cost per patient was $229 higher with pregabalin 150 mg BID than placebo, whereas pregabalin 225 mg BID was $866 less costly than placebo. At 1 year, pregabalin was cost saving and more effective than placebo, duloxetine, tramadol, milnacipran, and gabapentin. Compared with amitriptyline, pregabalin was not cost-effective at both dosages, although when excluding old and methodologically weak studies of clinical effectiveness of amitriptyline, pregabalin 225 mg BID became cost saving and pregabalin 150 mg BID was cost-effective. LIMITATIONS: Comparisons between pregabalin and other active agents are based on indirect comparisons, not head-to-head trials, and so should be interpreted with caution. Limitations for comparators include an inability to access sub-group data, inconsistency of response definitions, inclusion of older trials, and absence of long-term studies. CONCLUSIONS: This model found pregabalin to be cost-effective in treating patients with severe fibromyalgia.

Medication dosing patterns associated with duloxetine and pregabalin among patients with fibromyalgia.

OBJECTIVE: To examine medication dosing patterns of duloxetine and pregabalin among patients with fibromyalgia. METHODS: From a large US administrative claims database, commercially insured fibromyalgia patients aged 18-64 who initiated duloxetine or pregabalin in 2006 were selected. Initiation was defined as a 90-day medication gap, with the dispense date of the first initiation as the index date. All patients selected had continuous enrollment over the 12-month pre- and post-index periods, and were classified into the duloxetine or pregabalin cohorts based on their index agent. Initial daily dose, average daily dose over the 12-month post-index period, mean and median daily doses and daily costs of each of the first 12 prescriptions were examined for both the duloxetine and pregabalin cohorts. RESULTS: Both the duloxetine (n = 3773) and pregabalin (n = 4189) cohorts had a mean age of 50 years (median age: 52 vs. 53). The average initial daily dose was 55.7 mg for duloxetine and 161.5 mg for pregabalin. Over the 12-month post-index period, the average daily dose per patient was 55.6 mg for duloxetine and 195.7 mg for pregabalin. The average daily doses for the first 12 duloxetine prescriptions ranged 55.7-60.3 mg, with the mean daily costs between $3.77 and $4.59. For the first 12 pregabalin prescriptions, the average daily dose increased from 161.5 mg to 282.4 mg, while the average daily costs ranged between $4.30-4.61. CONCLUSIONS: Among patients with fibromyalgia, duloxetine and pregabalin initiators had different dosing patterns. The average daily dose for duloxetine was relatively stable over time, while pregabalin patients had significant dose increase over the 12-month post-index period.

Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia.

OBJECTIVE: The purpose of this study was to compare the cost effectiveness of a new 8% capsaicin patch, compared to the current treatments for postherpetic neuralgia (PHN), including tricyclic antidepressants (TCAs), topical lidocaine patches, duloxetine, gabapentin, and pregabalin. METHODS: A 1-year Markov model was constructed for PHN with monthly cycles, including dose titration and management of adverse events. The perspective of the analysis was from a payer perspective, managed-care organization. Clinical trials were used to determine the proportion of patients achieving at least a 30% improvement in PHN pain, the efficacy parameter. The outcome was cost per quality-adjusted life-year (QALY); second-order probabilistic sensitivity analyses were conducted. RESULTS: The effectiveness results indicated that 8% capsaicin patch and topical lidocaine patch were significantly more effective than the oral PHN products. TCAs were least costly and significantly less costly than duloxetine, pregabalin, topical lidocaine patch, 8% capsaicin patch, but not gabapentin. The incremental cost-effectiveness ratio for the 8% capsaicin patch overlapped with the topical lidocaine patch and was within the accepted threshold of cost per QALY gained compared to TCAs, duloxetine, gabapentin, and pregablin. The frequency of the 8% capsaicin patch retreatment assumption significantly impacts its cost-effectiveness results. There are several limitations to this analysis. Since no head-to-head studies were identified, this model used inputs from multiple clinical trials. Also, a last observation carried forward process was assumed to have continued for the duration of the model. Additionally, the trials with duloxetine may have over-predicted its efficacy in PHN. Although a 30% improvement in pain is often an endpoint in clinical trials, some patients may require greater or less improvement in pain to be considered a clinical success. CONCLUSIONS: The effectiveness results demonstrated that 8% capsaicin and topical lidocaine patches had significantly higher effectiveness rates than the oral agents used to treat PHN. In addition, this cost-effectiveness analysis found that the 8% capsaicin patch was similar to topical lidocaine patch and within an accepted cost per QALY gained threshold compared to the oral products.

Retrospective evaluation of clinical characteristics, pharmacotherapy and healthcare resource use among patients prescribed pregabalin or duloxetine for diabetic peripheral neuropathy in usual care.

OBJECTIVE: To evaluate treatment patterns and costs among patients with painful diabetic peripheral neuropathy (pDPN) newly prescribed pregabalin or duloxetine in usual care settings. METHODS: Using the PharMetrics® Database, patients with pDPN (ICD-9-CM codes 357.2 or 250.6x) newly prescribed pregabalin or duloxetine were identified. Patients initiated on duloxetine (n=713; mean age 55.4 ± 9.5 years) were propensity score-matched with patients initiated on pregabalin (n=713; mean age 56.3 ± 9.3 years). Prevalence of comorbidities, pain-related pharmacotherapy and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 12 months preceding (pre-index) and following (follow-up) the date of the first pregabalin or duloxetine prescription. RESULTS: Both cohorts had multiple comorbidities and a substantial pain medication burden. Among pregabalin patients, use of other anticonvulsants (35.6% vs. 24.7%) and tricyclic antidepressants significantly decreased (18.2% vs. 13.7%) and serotonin-norepinephrine reuptake inhibitors (SNRIs) increased (7.9 % vs. 12.9%) in the follow-up period; all P values <0.05. Among duloxetine patients, use of other SNRIs (8.7% vs. 5.2%) and selective serotonin reuptake inhibitors decreased significantly (32.1% vs. 18.9%) in the follow-up period, but there were increases for anticonvulsants (42.1% vs. 48.4%), benzodiazepines (25.5% vs. 32%), and sedative/hypnotics (22.6% vs. 25.8%); all P values <0.05. Among pregabalin and duloxetine patients there were increases (P<0.05) in pharmacy, outpatient, and total healthcare costs from the pre-index to the follow-up period. Total medication costs in the follow-up period were significantly higher for duloxetine (median $6,763 [IQR $3,970-$10,914]) relative to pregabalin (median $6,059 [IQR $3,277-$9,865]); P=0.0017. CONCLUSIONS: Patients with pDPN prescribed pregabalin and duloxetine were characterized by a substantial comorbidity and pain medication burden. Although there were no differences in total healthcare costs, medication costs were significantly higher in the duloxetine cohort relative to the pregabalin cohort.

Modeling dropout from adverse event data: impact of dosing regimens across pregabalin trials in the treatment of generalized anxiety disorder.

Dizziness represents a major determinant of dropout in the treatment of generalized anxiety disorder with pregabalin. Titration (dose escalation) regimens based on clinical judgment were implemented to mitigate this adverse event and reduce patient dropout across clinical trials. Dropout is an important treatment failure endpoint, which can be analyzed using time-to-event models that incorporate daily dosing or other time-varying information. A parametric discrete-time dropout model with daily dizziness severity score as a covariate afforded a systematic, model-based assessment of titration dosing strategies, with model predictions evaluated against corresponding nonparametric estimates. A Gompertz hazard function adequately described the decreasing dropout hazard over time for individuals with severe or moderate dizziness and a lower, constant hazard for individuals reporting no dizziness or mild dizziness. Predictive performance of the model was adequate based on external validation with an independent trial and other goodness-of-fit criteria. Prospective simulations highlight the utility of this approach in reducing dropout based on examination of untested titration scenarios for future generalized anxiety disorder or other trials.

Pregabalin and gabapentin in matched patients with peripheral neuropathic pain in routine medical practice in a primary care setting: Findings from a cost-consequences analysis in a nested case-control study.

BACKGROUND: Pregabalin and gabapentin are marketed to treat peripheral neuropathic pain, but head-to-head comparison is lacking. OBJECTIVES: The aims of this work were to compare the effects of pregabalin and gabapentin on different patient-reported health outcomes and to analyze health care and nonhealth-care resource consumption and their related costs among patients treated for peripheral neuropathic pain in primary medical care. METHODS: A cost-consequences comparison in subjects with refractory (suboptimal response to > or =1 previous analgesic treatment for >6 months) chronic peripheral neuropathic pain was carried out using data extracted from two 12-week, observational, prospective studies in primary medical care. Patients were eligible if they were aged > or =18 years, had a score of > or =4 on the Douleur Neuropathique 4 questionnaire, and were able to complete health questionnaires written in Spanish. A nested-paired case-control design was chosen to perform the comparison with 2 controls (pregabalin) per case (gabapentin) matched by age, sex, peripheral neuropathic pain condition, time since diagnosis, number of previous treatments, pain intensity, depressive and anxiety symptom scores, and health state. Adult subjects with refractory chronic pain because of diabetic neuropathy, postherpetic or trigeminal neuralgias, or cervical or lumbosacral radiculopathies were included. Epidemiologic statistical methods were applied for comparing health effects (pain intensity, sleep, anxiety and depressive symptoms, disability, and health state), resources utilization, and related cost variations after 12 weeks. Indirect costs were measured by means of lost-workday equivalent calculations multiplied by the mean national daily salary. RESULTS: Analysis included 44 patients treated with gabapentin (cases) and 88 patients treated with pregabalin (controls) who were matched for age, sex, and other parameters. The mean (SD) gabapentin and pregabalin doses were 1263 (540) and 202 (119) mg/d, respectively. Although there was a greater reduction in last-week mean pain intensity with pregabalin (visual analog scale: 39.1 [22.5] vs 28.0 [22.2] mm; P = 0.008), as well as more patients with a > or =50% reduction in pain rate (60.9% vs 40.5%; P = 0.029), there were no significant differences between groups for sensory, affective, total, or present pain intensity. The significantly higher drug cost associated with pregabalin was offset by a greater reduction in productivity costs compared with gabapentin, yielding similar cost reduction (-euro1254 [1479] vs -euro1384 [2874], respectively; P = NS). CONCLUSION: Pregabalin appeared to be associated with greater reduction in mean weekly intensity of pain, but there were no significant differences in cost.

Comparing healthcare costs of Medicaid patients with postherpetic neuralgia (PHN) treated with lidocaine patch 5% versus gabapentin or pregabalin.

OBJECTIVE: To compare healthcare resource utilization and costs of postherpetic neuralgia (PHN) patients initiating lidocaine patch 5% (lidocaine patch) or oral gabapentin/pregabalin. METHODS: Patients with PHN diagnosis, or herpes zoster diagnosis and ≥30 days PHN-recommended treatment were selected from de-identified Medicaid claims data from Florida, Iowa, Missouri, and New Jersey, 1999-2007. Patients initiated monotherapy with lidocaine patch or gabapentin/pregabalin after PHN diagnosis, had continuous eligibility 6 months before (baseline) and 6 months after (study period) medication index date, and were ≥18 years old. Lidocaine patch patients were matched to gabapentin/pregabalin patients based on their propensity to initiate treatment. Study period resource utilization and costs from a Medicaid perspective were compared between treatment groups using univariate analysis. RESULTS: Matched patients were on average 61.3 years old, approximately 73% were women, and 55% had other painful conditions during the baseline period. 6-month per patient PHN-related prescription drug costs were similar for matched lidocaine patch (n=312) and gabapentin/pregabalin (n=312) patients ($854 vs. 820, p=0.75), while PHN-related medical costs appeared lower in the lidocaine patch group ($145 vs. 353, p=0.12). Furthermore, there were no statistically significant differences between treatment groups during the observation period in overall resource utilization, total prescription drug costs, and total medical costs per patient. CONCLUSIONS: In spite of higher list prices, PHN patients treated with lidocaine patch cost no more than patients treated with gabapentin or pregabalin in terms of overall healthcare costs over the 6-month study period. The study suggests that PHN-related medical costs may be lower among lidocaine patch patients. LIMITATIONS: Findings are based on a Medicaid sample and may not be generalizable to all PHN patients.