Real-world hospitalization risk in patients with epilepsy treated with perampanel.

AIM: The aim of this study was to evaluate the risk of hospitalization and emergency department admission following initiation of perampanel treatment in patients with epilepsy. METHODS: This study is a retrospective longitudinal cohort study (Optum® Clinformatics® Datamart). Patients 4 to 11 years of age with a diagnosis of partial onset seizures or ≥12 years of age with primary generalized tonic-clonic seizures who had ≥1 perampanel prescription between 1/1/2014 and 3/31/2018 were eligible for the study. Additionally, patients were required to have 12-months of continuous enrollment before (pre-) and after (post-) the date of the first perampanel prescription (index-date). One-year relative-risks of all-cause and epilepsy-related hospitalizations and emergency department (ED) visits were estimated following initiation of perampanel treatment. Outcomes were also evaluated among a subsets of patients who were adherent to perampanel treatment, defined as a Medication Possession Ratio (MPR) ≥80%. RESULTS: A total of 320 patients were included in the study, mean age 38.2 ±â€¯19 years, 56.6% female. In the overall population, the relative risks of hospitalizations or ED visits after perampanel initiation were not significantly different. Among the 145 patients who had an MPR ≥80%, initiation of perampanel treatment resulted in a significantly lower risk of epilepsy-related hospitalization (relative risk [RR] = 0.68, confidence interval [CI] [0.47, 0.98]), all-cause ED visits (RR = 0.80, CI [0.66, 0.98]), and epilepsy-related ED visits (RR = 0.74, CI [0.57, 0.95]) in the follow-up period. CONCLUSIONS: Adherence to perampanel treatment was associated with significant reductions in one-year hospitalizations and ED visit risk in real world settings.

Association Between State Medicaid Eligibility Thresholds and Deaths Due to Substance Use Disorders.

Importance: The United States is currently facing an epidemic of deaths related to substance use disorder (SUD), with totals exceeding those due to motor vehicle crashes and gun violence. The epidemic has led to decreased life expectancy in some populations. In recent years, Medicaid eligibility has expanded in some states, and the association of this expansion with SUD-related deaths is yet to be examined. Objective: To examine the association between eligibility thresholds for state Medicaid coverage and SUD-related deaths. Design, Setting, and Participants: Economic evaluation study using a retrospective analysis of state-level data between 2002 and 2015 to determine the association between the Medicaid eligibility threshold and SUD-related deaths, controlling for other relevant policies, state socioeconomic characteristics, fixed effects, and a time trend. Policy variables were lagged by 1 year to allow time for associations to materialize. Data were collected and analyzed from 2016 to 2017. Exposures: The policy of interest was the state Medicaid eligibility threshold, ie, the highest allowed income that qualifies a person for Medicaid, expressed as a percentage of the federal poverty level. State policies related to mental health, overdose treatment, and law enforcement of drug crimes were included as controls. Main Outcomes and Measures: The primary outcome was number of SUD-related deaths, obtained from data provided by the Centers for Disease Control and Prevention. Results: Across 700 state-year observations, the mean (SD) number of SUD-related deaths was 21.15 (6.05) per 100 000 population. Between 2002 and 2015, the national SUD-related death rate increased from 16.0 to 27.5 per 100 000, while the average Medicaid eligibility threshold increased from 87.2% to 97.1% of the federal poverty level. Over this period, every 100-percentage point increase in the Medicaid eligibility threshold (eg, from 50% to 150% of the federal poverty level) was associated with 1.373 (95% CI, -2.732 to -0.014) fewer SUD-related deaths per 100 000 residents, a reduction of 6.50%. In the 22 states with net contractions in eligibility thresholds between 2005 and 2015, an estimated increase of 570 SUD-related deaths (95% CI, -143 to 1283) occurred. In the 28 states that increased eligibility thresholds, an estimated 1045 SUD-related deaths (95% CI, -209 to 2299) may have been prevented. Conclusions and Relevance: These findings suggest that the overall increase in SUD-related deaths between 2002 and 2015 may have been greater had the average eligibility threshold for Medicaid not increased over this period. Broader eligibility for Medicaid coverage may be one tool to help reduce SUD-related deaths.

Treatment Patterns, Healthcare Resource Utilization and Costs Among Schizophrenia Patients Treated with Long-Acting Injectable Versus Oral Antipsychotics.

INTRODUCTION: Long-acting injectable (LAI) antipsychotic use may reduce healthcare resource utilization compared with oral antipsychotic use by improving adherence and reducing dosing frequency. Our goal was to examine treatment patterns, healthcare utilization, and costs among recently diagnosed schizophrenia patients receiving oral versus LAI antipsychotics. METHODS: The MarketScan Multi-state Medicaid database was used to identify schizophrenia patients aged ≥ 18 years who received an LAI or oral antipsychotic between January 1, 2011 and December 31, 2014. Primary outcomes included treatment patterns such as adherence (measured as proportion of days covered-PDC), persistence, discontinuation, switching, and healthcare resource utilization and costs. Propensity score matching (PSM) was used to control for differences in baseline characteristics between the cohorts. Outcomes were assessed over a 12-month post-index period and compared between treatment cohorts. RESULTS: After PSM, 2302 patients were included in each of the LAI and oral antipsychotics cohorts. There were no differences in PDC or therapy switching between the two cohorts. Compared with the oral cohort, patients receiving LAIs had lower discontinuation rates (46.1 vs. 61.6%, p < 0.001), fewer inpatient admissions (0.5 vs. 0.9, p < 0.001), hospital days (3.9 vs. 6.5, p < 0.001), and ER visits (2.4 vs. 2.9, p = 0.007), and a higher number of prescription fills (29.5 vs. 25.3, p < 0.001). Patients prescribed LAIs had lower monthly inpatient ($US4007 vs. 8769, p < 0.001) and ER visits costs ($682 vs. 891, p < 0.001) but higher monthly medication costs ($10,713 vs. $655, p < 0.001) compared with the oral cohort over the 12-month post-index period. Overall, both cohorts had similar total medical costs (LAI vs. oral: $24,988 vs. 23,887, p = 0.354) during the follow-up period. CONCLUSION: Patients receiving LAIs were more likely to remain on medication compared with the oral group, which may account for reduced inpatient admissions. Hospitalization cost reductions offset the higher costs of LAI medications, resulting in no increase in total healthcare costs relative to oral antipsychotic use. FUNDING: Alkermes Inc.

Healthcare utilization and costs associated with treatment for opioid dependence.

OBJECTIVE: Opioid use disorder (OUD) can be managed with medication assisted therapy (MAT) (methadone [MET], buprenorphine [BUP], or extended-release naltrexone [XR-NTX]) or counseling alone (non-pharmacological therapy [NPT]). The objective of this study was to evaluate healthcare resource utilization and costs associated with XR-NTX compared with alternative treatments for opioid dependence. METHODS: Adults with a diagnosis of opioid dependence who initiated treatment with XR-NTX, BUP, MET, or NPT between January 1, 2011 and December 31, 2014 were identified in the Truven Health MarketScan Commercial administrative claims database. Healthcare resource utilization, costs (inpatient [IP], emergency department [ED], outpatient [OP], and pharmacy) and adherence were evaluated for each cohort during 12-month baseline and follow-up periods. RESULTS: A total of 29,235 patients were included in the analysis; 1,041, 20,566, 745, and 6,883 received XR-NTX, BUP, MET, and NPT, respectively. Patients in the XR-NTX cohort were significantly younger and had more comorbidities compared with the other cohorts. Patients in the XR-NTX group had the largest percentage decrease in IP and ED utilization and costs from baseline to follow-up. OP and pharmacy costs increased significantly from baseline to follow-up for all cohorts. Overall, there was no significant change in total healthcare costs for the XR-NTX group, whereas the costs increased significantly for other groups (BUP = +43%, MET = +47.7%, NPT = +38.8%). CONCLUSIONS: Healthcare resource utilization and costs increased from baseline to follow-up in BUP, MET, and NPT patients, whereas patients receiving XR-NTX experienced no such increase. This analysis suggests there may be economic value in the use of XR-NTX for OUD.

Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings.

OBJECTIVE: To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). METHODS: The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. RESULTS: Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. CONCLUSIONS: Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.

Therapy switching, augmentation, and discontinuation in patients with osteoarthritis and chronic low back pain.

BACKGROUND: Recommended pain treatments for osteoarthritis (OA) and chronic low back pain (CLBP) are suboptimal, and limited information is available regarding patterns of pharmacotherapy among patients with these conditions. AIMS: Evaluate patterns of therapy switching, augmentation, and discontinuation after treatment initiation with select pain medications in patients with OA and CLBP. METHODS: Using the U.K. The Health Improvement Network (THIN) database, OA and CLBP patients newly prescribed (index-event) nonselective nonsteroidal anti-inflammatory drugs (NS-NSAIDs), cyclooxygenase-2 inhibitors (Cox-2s), acetaminophen, tramadol and weak or strong opioids were selected. Descriptive statistics, Kaplan-Meier analyses, and COX proportional hazards models were used to evaluate patterns of changes in pharmacotherapy during the 12-month postindex period. RESULTS: Rates of therapy switching, augmentation, and discontinuation, respectively, were significantly different (all P values<0.0001) across the evaluated medication cohorts for both OA and CLBP patients. Discontinuation rates in OA patients were 91.9% (NS-NSAIDs), 86.9% (Cox-2s), 91.4% (acetaminophen), 89.7% (tramadol), 93.2% (weak opioids), and 84.3% (strong opioids); and in CLBP patients were 97.2% (NS-NSAIDs), 94.0% (Cox-2s), 95.0% (acetaminophen), 92.8% (tramadol), 97.0% (weak opioids), and 86.8% (strong opioids). The rates of switching (range 30.0% to 59.6%) and augmentation (range 7.5% to 15.2%) were lower. Estimated probability evaluations suggested that two-thirds of patients who switched, augmented, or discontinued therapy did so within the first couple of months, and a majority did so within 6-months of treatment initiation. CONCLUSIONS: This study demonstrates that therapy switching and discontinuation of select pain medications were common among OA and CLBP patients in the U.K. and may result from inadequate pain relief or undesirable side effects.

Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants.

OBJECTIVE: To examine treatment patterns and costs among patients with fibromyalgia prescribed pregabalin or tricyclic antidepressants (TCAs). METHODS: Using the LifeLink™ Health Plan Claims Database, patients with fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed (index date) TCAs (n = 898) were identified and propensity score-matched (PSM) with patients newly prescribed pregabalin (n = 898). Pain-related pharmacotherapy, comorbidities, and healthcare resource use/costs were examined during the 12 months, pre-index, and follow-up periods. RESULTS: Both patient groups reported multiple comorbidities and received pain medications in the pre-index and follow-up periods. Among patients prescribed pregabalin, use of non-selective non-steroidal anti-inflammatory drugs (43.3% vs 39.8%), other anticonvulsants (28.6% vs 23.3%), and tetracyclic/miscellaneous antidepressants (28.5% vs 25.8%) significantly decreased, and cyclooxygenase 2 (COX-2) inhibitors (7.7% vs 10.4%), TCAs (4.8% vs 7.9%), and topical agents (10.8% vs 15.1%) increased in the follow-up period (p < 0.05). Among patients prescribed TCAs, there were significant decreases in muscle relaxants (42.0% vs 38.4%) and sedative hypnotics (27.4% vs 23.9%), and increases in COX-2 inhibitors (5.8% vs 7.9%) and anticonvulsants (25.1% vs 33.7%; p < 0.05). There were increases (p < 0.0001) in pharmacy costs in both cohorts and total healthcare costs in the pregabalin cohort from pre-index to follow-up. Median total costs were higher (p < 0.05) in the pregabalin group vs TCAs in the pre-index ($9935 vs $8771) and follow-up ($10,689 vs $8379) periods. LIMITATIONS: Despite attempts to address bias through PSM, the higher pre-index costs in the pregabalin cohort suggest a channeling of patients with more severe fibromyalgia to pregabalin. CONCLUSIONS: Patients with fibromyalgia prescribed pregabalin or TCAs had multiple comorbidities and a sizeable pain medication burden, which increased in the follow-up period for both cohorts. Only 5% of pregabalin initiators had been treated with concomitant TCAs at baseline, suggesting that TCAs were inappropriate for these patients owing to their contraindications.

Clinical comorbidities, treatment patterns, and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care.

OBJECTIVE: To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings. METHODS: Using the LifeLink™ Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n = 826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods. RESULTS: Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p < 0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p < 0.0001). There were significant increases (p < 0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p = 0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods. LIMITATIONS: Limitations of this study are typical of those associated with retrospective database analyses. CONCLUSIONS: Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups.

The burden of chronic low back pain: clinical comorbidities, treatment patterns, and health care costs in usual care settings.

STUDY DESIGN: Retrospective analysis of an insurance claims database. OBJECTIVE: To examine the comorbidities, treatment patterns, health care resource utilization, and direct medical costs of patients with chronic low back pain (CLBP) in clinical practice. SUMMARY OF BACKGROUND DATA: Although the socioeconomic impact of CLBP is substantial, characterization of comorbidities, pain-related pharmacotherapy, and health care resource use/costs of patients with CLBP relative to non-CLBP controls have been infrequently documented. METHODS: Using the LifeLink Health Plan Claims Database (IMS Health Inc., Watertown, MA), patients with CLBP, defined using the International Classification of Diseases, Ninth Revision, Clinical Modification, were identified and matched (age, sex, and region) with non-CLBP individuals. Comorbidities, pain-related pharmacotherapy, and health care service use/costs (pharmacy, outpatient, inpatient, total) were compared for the 2 groups during 2008. RESULTS: A total of 101,294 patients with CLBP and controls were identified (55% women; mean age was 47.2 ± 11.6 years). Relative to controls, patients with CLBP had a greater comorbidity burden including a significantly higher (P < 0.0001) frequency of musculoskeletal and neuropathic pain conditions and common sequelae of pain such as depression (13.0% vs. 6.1%), anxiety (8.0% vs. 3.4%), and sleep disorders (10.0% vs. 3.4%). Pain-related pharmacotherapy was significantly greater (P < 0.0001) among patients with CLBP including opioids (37.0% vs. 14.8%; P < 0.0001), nonsteroidal anti-inflammatory drugs (26.2% vs. 9.6%; P < 0.0001), and tramadol (8.2% vs. 1.2%; P < 0.0001). Prescribing of "adjunctive" medications for treating conditions associated with pain (i.e., depression, anxiety, and insomnia) was also significantly greater (P < 0.0001) among patients with CLBP; 36.3% of patients received combination therapy. Health care costs were significantly higher in the CLBP cohort (P < 0.0001), reflecting greater resource utilization. Total direct medical costs were estimated at $8386 ± $17,507 in the CLBP group and $3607 ± $10,845 in the control group; P < 0.0001). CONCLUSION: Patients with CLBP are characterized by greater comorbidity and economic burdens compared with those without CLBP. This economic burden can be attributed to greater prescribing of pain-related medications and increased health resource utilization.

Patterns of therapy switching, augmentation, and discontinuation after initiation of treatment with select medications in patients with osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a debilitating condition characterized by chronic pain. Several pain medications are recommended, and patients frequently alternate among these medications. OBJECTIVES: The purpose of this study was to examine the use of pain medications in clinical practice with respect to recommended guidelines. This objective was accomplished by evaluating patterns of switching, augmentation, and discontinuation after treatment initiation with select medications in patients with OA. METHODS: The LifeLink Health Plan Claims Database was used to select patients with OA (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 715.XX) who were newly prescribed (index event) nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 inhibitors, acetaminophen, tramadol, weak opioids, and strong opioids. Descriptive statistics, Kaplan-Meier analyses, and the COX proportional hazards model were used to assess therapy switching, augmentation, and discontinuation during the 12-month postindex period. Patterns of intraarticular injections and joint replacement surgeries among the cohorts were also evaluated. RESULTS: Substantial proportions of OA patients switched, augmented, or discontinued therapy during the postindex period. Rates of therapy switching, augmentation, and discontinuation, respectively, were significantly different (all P < 0.0001 for overall effects using log-rank tests) across the evaluated medication cohorts: NSAIDs, 22.3%, 6.7%, 93.2%; COX-2 inhibitors, 27.5%, 10%, 87.4%; acetaminophen, 46.0%, 6.5%, 98.7%; tramadol, 44.5%, 8.4%, 95.6%; weak opioids, 27.2%, 4.1%, 98.3%; and strong opioids, 41.1%, 3.3%, 97%. Therapy switching, augmentation, and discontinuation occurred within 2 months after treatment initiation in two thirds of patients and within 6 months in >90% of patients. The patterns of intraarticular injections were significantly different across treatment cohorts, as were the patterns of joint replacement surgeries (both P < 0.0001 for overall effects using log-rank tests), with average times to surgery that appeared longer with acetaminophen, NSAIDs, and COX-2 inhibitor initiators (416-447 days) than with tramadol and opioids (354-385 days). CONCLUSIONS: Results indicate that therapy switching and discontinuation were frequent among OA patients initiating treatment with the currently recommended medication classes and might suggest suboptimal pain relief or potentially intolerable therapy-related side effects.

Clinical comorbidities, treatment patterns, and direct medical costs of patients with osteoarthritis in usual care: a retrospective claims database analysis.

OBJECTIVE: Comorbidities and resource utilization among patients with osteoarthritis (OA) in clinical practice have been infrequently characterized. The purpose of this study was to examine comorbidities, pain-related pharmacotherapy, and direct medical costs of patients with OA in clinical practice. METHOD: This retrospective cohort analysis used medical and pharmacy claims data from the LifeLink™ Database. OA patients (ICD-9-CM codes 715.XX) were matched (age, gender, and region) with individuals without OA. Comorbidities, pain-related pharmacotherapy, and direct medical costs (pharmacy, outpatient, inpatient, total) were examined for the calendar year 2008. RESULTS: The sample consisted of 112,951 OA patients and 112,951 controls (mean age: 56.9 [SD=9.5] years; 62% female). Relative to controls, OA patients were significantly more likely (p<0.0001) to have comorbidities, including musculoskeletal (84.3 vs. 37.1%) and neuropathic pain (22.0 vs. 6.1%) conditions, depression (12.4 vs. 6.4%), anxiety (6.6 vs. 3.5%), and sleep disorders (11.9 vs. 4.2%). OA patients were significantly more likely (p<0.0001) to receive pain-related medications, including opioids (40.7 vs. 17.1%), NSAIDs (37.1 vs. 11.5%), tramadol (9.8 vs. 1.8%), and adjunctive medications for treating depression, anxiety, and insomnia. Mean [SD] total direct medical costs were more than two times higher among OA patients ($12,905 [$21,884] vs. $5099 [$13,855]; p<0.001) and median costs were more than three times higher ($6188 vs. $1879; p<0.0001). Study limitations include potential errors in coding and recording; overestimation of the comorbidity burden; inability to link condition of interest, OA, with prescribed medications; and possible underestimation of the true costs of OA, because indirect costs were not considered and the direct costs were from a third party payer (commercial insurance) perspective. CONCLUSION: The patient burden of OA was characterized by a high prevalence of comorbidities. The payer burden was also substantial, with significantly greater use of pain-related and adjunctive medications, and higher direct medical costs.

Clinical characteristics, pharmacotherapy, and healthcare resource use among patients with diabetic neuropathy newly prescribed pregabalin or gabapentin.

OBJECTIVE: To characterize comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with painful diabetic peripheral neuropathy (pDPN) newly prescribed pregabalin or gabapentin in clinical practice. METHODS: Using the LifeLink(™) Health Plan Claims Database, patients with pDPN (ICD-9-CM codes 357.2 or 250.6) newly prescribed (index event) gabapentin (n = 1,178; 56.9 ± 10.3 years old) were identified and propensity score-matched with patients initiated on pregabalin (n = 1,178; 56.4 ± 9.8 years old). Comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods. RESULTS: Both cohorts were characterized by multiple comorbidities and substantial use of pain-related and adjunctive medications. In the pregabalin cohort, the use of tricyclic antidepressants significantly decreased (16.0% vs. 13.2%) and nonsteroidal anti-inflammatory drugs (30.8% vs. 34.8%), muscle relaxants (19.2% vs. 22.9%), anticonvulsants (14.4% vs. 18.1%), benzodiazepines (22.3% vs. 25.0%), and topical agents (7.0% vs. 9.8%) increased (P < 0.05) in the follow-up period. In the gabapentin cohort, there were significant increases (P < 0.05) in the use of short-acting (55.4% vs. 61.2%) and long-acting (9.4% to 12.8%) opioids, serotonin-norepinephrine re-uptake inhibitors (14.2% vs. 16.7%), anticonvulsants (7.1% vs. 19.2%), benzodiazepines (19.1% vs. 24.3%), sedative/hypnotics (14.9% vs. 18.0%), and tramadol (13.3% vs. 16.8%). There were significant increases (P < 0.05) in pharmacy, outpatient, and total costs in both cohorts and in costs of physician office visits in the gabapentin cohort. There was no difference in postindex median total costs between the pregabalin and gabapentin cohorts ($16,137 vs. $15,766). CONCLUSIONS: Patients with pDPN prescribed pregabalin and gabapentin had a substantial comorbidity and pain medication burden. Although healthcare costs increased in both groups, the increase in pain medication burden was higher in the gabapentin group. Direct medical costs were similar for both groups. Given the human and economic burden of pDPN, future research may benefit from a focus on efficacy parameters to further differentiate treatment options.

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.

Initial use of pregabalin, patterns of pain-related pharmacotherapy, and healthcare resource use among older patients with fibromyalgia.

OBJECTIVE: To characterize the comorbidities, pain-related pharmacotherapy, and healthcare resource use among older patients with fibromyalgia (FM) newly prescribed pregabalin in clinical practice. METHODS: Using the PharMetrics database, patients with FM aged 65 or more years (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) who were newly prescribed pregabalin (index event) on or after July 1, 2007, were identified (N = 98, mean age 72.4 +/- 6.4 years; 81.6% female). Prevalence of comorbidities, pharmacotherapy, and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 6-month preindex and postindex periods. RESULTS: Patients had a variety of comorbidities including various disorders generally associated with an older population, such as hypertension (41.8%), diabetes (22.5%), and coronary artery disease (15.3%). On average, patients received 3.3 +/- 2.3 pregabalin prescriptions; the average number of days of therapy was 121 +/- 88.9. Patients had a high medication burden in both the pre- and postindex periods; opioids were the most commonly prescribed medications (54.1% vs 59.2%); combination therapy was also common, with opioids and antidepressants the most frequent (35% in both periods). Except for the use of selective serotonin reuptake inhibitors, which decreased significantly in the postindex period (24.5% vs 19.4%, P = .0253), there were no changes in use of any of the other medications, including nonsteroidal anti-inflammatory drugs (36.7% vs 32.7%), tramadol (17.4% vs 24.5%), muscle relaxants (18.4% vs 21.4%), tricyclic antidepressants (21.4% vs 18.4%), serotonin and norepinephrine reuptake inhibitors (10.2% vs 12.2%), and anticonvulsants (17.4% vs 21.4%) after initiation of pregabalin therapy. There were decreases in the number of physician office visits and total outpatient visits (both P <.01) and in the proportion of patients with visits to physical therapists (21.4% vs 12.2%, P = .0201); however, there were no changes in healthcare costs (pharmacy, outpatient, inpatient, or total) from the pre- to postindex period. CONCLUSIONS: These results suggest a substantial medication and comorbidity burden in older patients with FM. Although it is not possible to establish cause-and-effect relationships in claims database studies, results also suggest that the initiation of pregabalin was cost-neutral. Further evaluation is warranted to characterize FM and determine appropriate management strategies in this fragile population.

Clinical characteristics, pharmacotherapy and healthcare resource use among patients with fibromyalgia newly prescribed gabapentin or pregabalin.

OBJECTIVE: To characterize comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or gabapentin in clinical practice. METHODS AND DESIGN: Using the PharMetrics Database, FM patients (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed pregabalin (n = 1,606; mean age 49.9 +/- 9.6 years; 87.9% female) and gabapentin (n = 930; mean age 49.5 +/- 9.6 years; 86.6% female) on/after July 1, 2007 were identified. Prevalence of comorbidities, pharmacotherapy, and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 6 months preceding (preindex) and following (postindex) the date of their first pregabalin or gabapentin (index) prescription. RESULTS: Patients in both cohorts had a variety of comorbidities and used multiple medications. There were significant decreases (P values < 0.05) in the use of nonsteroidal anti-inflammatory drugs (32.1% vs. 29.5%), anticonvulsants (27.0% vs. 22.0%), and combination therapies in the pregabalin cohort in the postindex period. There were significant increases (all P values < 0.05) in use of short-acting opioids (58.8% vs. 63.7%), any opioids (61.5% vs. 65.6%), serotonin-norepinephrine reuptake inhibitors (22.5% vs. 24.5%), anticonvulsants (16.3% vs. 26.2%), benzodiazepines (33.2% vs. 36.6%), topical agents (6.6% vs. 9.0%), and combination therapies in the gabapentin cohort. Although there were no changes in units of healthcare resources used, there were increases in the postindex period in hospitalization, medications, and total costs for pregabalin, and office visits and medication costs for gabapentin (all P values < 0.05). CONCLUSIONS: Results suggest a high comorbidity and medication use burden in FM patients in this study. Further evaluation is warranted to clarify differences in resource utilization/costs observed with these two anticonvulsants.

Selecting an appropriate medication for treating neuropathic pain in patients with diabetes: a study using the U.K. and Germany Mediplus databases.

OBJECTIVE: To evaluate the appropriateness of prescribing select neuropathic pain medications to diabetes patients based on the potential for drug-drug interactions with medications diabetes patients were prescribed continuously for > or =3 months (chronic use). METHODS: Medical records of patients with a diagnosis of diabetes or use of antidiabetic medications between January 1, 2002 and September 30, 2005 in the U.K. and Germany Mediplus databases were obtained. PATIENTS: Medication use profiles were evaluated between April 2004 and September 2005. The metabolic pathways associated with medications that were prescribed chronically to at least 10% of study patients were compared with the metabolic pathways of neuropathic pain medications to identify potential drug-drug interactions. RESULTS: A total of 40,448 patients in the U.K. (63.6 +/- 16.6 years, 51% male) and 31,930 patients in Germany (68.9 +/- 12.7 years, 46% male) were identified. Frequently prescribed medications in the U.K. included aspirin (33.7%), metformin (32.7%), simvastatin (25.5%), atorvastatin (19.4%), atenolol (18.1%), and in Germany hydrochlorothiazide (35.8%), aspirin (25.2%), metformin (21.6%), metoprolol (20.3%), and simvastatin (18.3%). Several neuropathic pain medications have potential for drug-drug interactions with medications prescribed to diabetes patients. Examples include (neuropathic pain medications vs. diabetes medications): duloxetine, paroxetine, and methadone (CYP2D6 inhibitors) and oxycodone HCL, hydrocodone (CYP2D6 substrates) vs. metoprolol and bisoprolol (CYP2D6 substrates); and carbamazepine (CYP3A4 inducer) vs. simvastatin, and atorvastatin (CYP3A4 substrates). CONCLUSIONS/INTERPRETATION: Our findings underscore the need for medical vigilance when selecting medications for treating neuropathic pain in diabetes patients.

A retrospective evaluation of the use of gabapentin and pregabalin in patients with postherpetic neuralgia in usual-care settings.

BACKGROUND: Both gabapentin and pregabalin are approved for the management of postherpetic neuralgia (PHN), although dosing and pharmacokinetic differences between these medications may affect their use in actual practice. OBJECTIVES: This study was conducted to characterize the use of gabapentin and pregabalin in the management of PHN in clinical practice, with a specific focus on the doses actually prescribed and changes in the use of other neuropathic pain-related medications after the initiation of gabapentin or pregabalin. METHODS: The PharMetrics Patient-Centric Database was used to identify patients with PHN who were newly prescribed gabapentin or pregabalin between September 1, 2005, and March 31, 2006. The out-comes of interest were the prevalence of comorbidities, exposure to neuropathic pain-related medications (ie, the proportions of patients receiving >or=1 prescription for these medications in the 6-month periods before and after the date of the first gabapentin or pregabalin prescription), and attainment of therapeutic dose levels (gabapentin, >or=1800 mg/d; pregabalin, >or=150 mg/d). RESULTS: The database search identified 151 patients with PHN who were newly prescribed gabapentin (57.0% female; mean [SD] age, 55.8 [11.3] years) and 100 patients who were newly prescribed pregabalin (62.0% female; mean age, 52.8 [9.4] years). The prevalence of comorbidities did not differ significantly between recipients of prescriptions for gabapentin or pregabalin, with the exception of hyperlipidemia, which was more prevalent in those prescribed gabapentin (33.8% vs 22.0%, respectively; P = 0.044), and depression, which was more prevalent in those prescribed pregabalin (12.0% vs 4.6%, respectively; P = 0.031). In the pretreatment period, those who were prescribed pregabalin had significantly greater use of long-acting opioids (P = 0.005), anticonvulsants (P < 0.001), selective norepinephrine reuptake inhibitors (P < 0.001), and the lidocaine 5% patch (P = 0.005) compared with those prescribed gabapentin. Use of any opioid increased from pretreatment to follow-up in those prescribed gabapentin, significantly so in those who received >or=2 opioid prescriptions (P = 0.016). Use of any opioid decreased significantly from pre-treatment to follow-up in those prescribed pregabalin (P = 0.005), particularly in those who received >or=2 opioid prescriptions (P = 0.004). Tramadol use decreased significantly in those prescribed gabapentin (P = 0.045), and anticonvulsant use decreased significantly in those prescribed pregabalin (P = 0.004). Among patients prescribed gabapentin or pregabalin who received 1 prescription, 2 consecutive prescriptions, and >or=3 consecutive prescriptions, a greater proportion of those prescribed pregabalin attained therapeutic dose levels by their first, second, and third consecutive prescriptions compared with those prescribed gabapentin (69.0% vs 3.5%, respectively [P < 0.001]; 71.4% vs 21.7% [P < 0.001]; and 89.3% vs 46.2% [P < 0.001], respectively). CONCLUSIONS: In these patients with PHN in the usual-care setting, opioid use increased after the initiation of gabapentin and decreased after the initiation of pregabalin. Few of those prescribed gabapentin received a prescription for a therapeutic dose, whereas a greater proportion of patients who were prescribed pregabalin received a prescription for a therapeutic dose.

Clinical characteristics and pain management among patients with painful peripheral neuropathic disorders in general practice settings.

Alleviating chronic pain is a global healthcare priority. Understanding the medical profile and current treatment patterns in patients with painful neuropathic disorders (PNDs) is crucial to the development of effective pain management strategies. Thus, our objective was to describe the demographic and clinical characteristics of persons with PNDs and their use of pain medications. Using the general practice research database, we categorized PNDs in two ways: Pure PNDs (which include diabetic neuropathy, postherpetic neuralgia, etc.; N=16,690) and Mixed PNDs (which include back/neck pain with neuropathic involvement; N=14,309). On average, PND patients were 55 years old (Pure, 55.4 [SD=16.9] years; Mixed, 54.3 [SD=16.4] years). Over a third had other chronic pain-related (Pure, 37.5%; Mixed, 37.1%) and nearly a quarter had non-pain related (Pure, 28.1%; Mixed, 24.1%) comorbidities. Use of medications with clinically demonstrated efficacy in PNDs was higher among patients with Pure PNDs (tricyclic antidepressants [Pure, 16.6%; Mixed, 10.1%]; 2nd generation antidepressants [Pure, 11.0%; Mixed, 9.7%]; and antiepileptics [Pure, 12.2%; Mixed, 2.6%]), whereas use of NSAIDs (Pure, 43.1%; Mixed, 65.2%) and opioids (Pure, 8.5%; Mixed, 14.3%) was higher among patients with Mixed PNDs. Average daily doses of select neuropathic pain-related medications among PND patients (Pure and Mixed) were lower than those recommended for neuropathic pain. Among both Pure and Mixed PND patients, use and doses of evidenced-based neuropathic pain-related medications was low, and lower than the use of NSAIDs (a medication class with no proven efficacy for PNDs) in each group, suggesting possible sub-optimal neuropathic pain management among these patients.

Burden of illness in painful diabetic peripheral neuropathy: the patients' perspectives.

UNLABELLED: Our goal was to assess the patient-level burden among subjects with painful diabetic peripheral neuropathy (DPN). Community-based physicians recruited patients with painful DPN (N = 255) between April and October 2003. Patients completed a survey on pain experience (Brief Pain Inventory-DPN [BPI-DPN]), health status (EuroQoL [EQ-5D]), healthcare utilization (consults, prescription [Rx], and over-the-counter [OTC] medications), and work productivity/functioning. Patients were 61 +/- 12.8 years old and had diabetes for 12 +/- 10.3 years and painful DPN for 6.4 +/- 6.4 years; 25.5 and 62.7% had other neuropathic and musculoskeletal pain conditions. Average and worst pain scores (BPI-DPN, 0-10 scales) were 5.0 +/- 2.5 and 5.6 +/- 2.8. The mean EQ-5D utility was .5 +/- .3 (range = -.594-1). A majority (87.4%) took pain medications (Rx/OTC) in the preceding week: an average of 3.8 +/- 3.9 Rx and 2.1 +/- 1.3 OTC medications. Nearly half (46.7%) received NSAIDs. Other frequently reported medications were short/long-acting opioids (43.1%), anticonvulsants (27.1%), selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors (18%), and tricyclic antidepressants (11.4%). During the preceding 3 months, 59.6% had >or=2 health professional consults; 59% reported decreased home productivity; 85.5% reported activity limitations; and 64.4% of patients who worked (N = 73) reported missing work/decreased work productivity due to painful DPN. Our results underscore a substantial patient-level burden among subjects with painful DPN. PERSPECTIVE: Information on the patient-level burden among painful DPN sufferers in the U.S. was previously lacking. Our results suggest that this burden is significant, evidenced by moderate-to-high pain levels, polypharmacy, health resource use, and work/activity limitations. Results also suggest suboptimal pain management and low levels of satisfaction with treatments.

Prevalence of contraindicated medical conditions and use of precluded medications in patients with painful neuropathic disorders prescribed amitriptyline.

Amitriptyline is a tricyclic antidepressant that is historically indicated and used to manage depression. More recently, due to clinical evidence demonstrating efficacy, it is often prescribed in the management of painful neuropathic disorders (PNDs). However, the amitriptyline label contains numerous preclusions (contraindications, warnings/precautions, drug interactions). Our objective was to measure the frequency of amitriptyline prescriptions in PND patients using the U.K. General Practice Research Database and assess whether any prescriptions were given to patients with preclusions listed in the product label. We identified a total of 13,546 patients (mean age 59 +/- 16.2 years; 66.7% female) who had a diagnosis of a PND and received > or =1 prescription for amitriptyline between July 1998 and June 2001. Nearly half (46.7%) of PND patients prescribed amitriptyline had > or =1 preclusion for its use; 3.5% had > or =1 contraindication; 22% had > or =1 warning/precaution; and 33% received > or =1 medication with a potential for drug interactions with amitriptyline. Preclusions were more likely in women than in men (48.3% vs. 43.4%, P < 0.0001); their incidence increased with age (42.8%, 50.4%, 55.1%, and 52.3% among those ages <65, 65-74, 75-84, and 85+ years, P < 0.0001), and the number of patients with preclusions was the highest in the phantom limb pain group (67.4%) and lowest in the atypical facial pain group (42.9%), P < 0.001. The average daily amitriptyline doses (starting: 33.6 +/- 32.4 mg; maintenance: 42.1 +/- 39.9 mg) were low compared to those used for the treatment of depression. Results indicate that, in a significant number of cases, the existence of preclusions did not prevent the prescribing of amitriptyline. Our findings raise a potential concern about the way this medication is being used. However, the clinical significance of these data is, as yet, unclear. Although, in theory, adverse outcomes may have been associated with this practice, we could not confirm this with this database analysis.