Economic burden of treatment-resistant depression among veterans in the United States.

OBJECTIVE: Evidence is limited on the economic burden associated with treatment-resistant depression (TRD) among US veterans. We evaluated the economic burden among patients with major depressive disorder (MDD) with and without TRD, and those without MDD in the Veterans Health Administration (VHA). METHODS: Three cohorts were identified using VHA claims data (01APR2014-31MAR2018). Patients with MDD (aged ≥18) who failed ≥2 antidepressant treatments of adequate dose and duration were defined as having TRD; patients with MDD not meeting this criterion constituted the non-TRD MDD cohort (index: first antidepressant claim). The non-MDD cohort included those without MDD diagnosis (index: randomly assigned). Patients with psychosis, schizophrenia, manic/bipolar disorder, or dementia in the 6-month pre-index period were excluded. Patients with non-TRD MDD and non-MDD were matched 1:1 to patients with TRD based on demographic characteristics (age, gender, race, index year). Health care resource utilization (HRU) and costs were analyzed during the post-index period using a negative binomial model and ordinary least squares regression model, respectively. RESULTS: After 1:1 exact matching, 10,449 patients were included in each cohort (mean age: 48.9 years). Patients with TRD had higher per patient per year (PPPY) HRU than non-TRD MDD (all-cause inpatient visits: incidence rate ratio [IRR]: 1.70 [95% confidence interval: 1.57-1.83]) and non-MDD (IRR: 5.04 [95% confidence interval: 4.51-5.63]), and incurred higher total all-cause health care costs PPPY than non-TRD MDD (mean difference: $5,906) and non-MDD (mean difference: $11,873; all p<.0001). CONCLUSION: Among US veterans, TRD poses a significant incremental economic burden relative to non-TRD MDD and non-MDD.

Treatment persistence and hospitalization rates among patients with schizophrenia: a quasi-experiment to evaluate a patient information program.

OBJECTIVE: The effective treatment of schizophrenia requires continuous antipsychotic maintenance therapy. However, poor persistence with treatment is common among patients with schizophrenia. The objective of this study was to compare persistence and hospitalization rates among patients with schizophrenia treated with long-acting injectable (LAI) antipsychotics (i.e. paliperidone palmitate and risperidone) and enrolled in a patient information program (program cohort) with patients treated with oral antipsychotics (OAs) who were not enrolled in a patient information program (nonprogram cohort). RESEARCH DESIGN AND METHODS: Using a quasi-experimental design, data from chart reviews (for program patients) and Medicaid claims (for nonprogram patients) was analyzed. Patients were eligible if they had ≥12 months of pre-index data, ≥6 months of post-index data, and no hospitalization at index. MAIN OUTCOME MEASURES: Persistence and hospitalization rates were assessed at 6 months post-index. Propensity score matching was used to control for observed differences in demographics and baseline clinical characteristics. Odds ratios (ORs) were calculated using generalized estimating equation models and adjusted for matched pairs and propensity score. RESULTS: A total of 102 program patients were matched to 408 nonprogram patients with similar baseline characteristics. Adjusted ORs indicated that the persistence rate at 6 months was significantly higher for the program cohort (88.2%) versus the nonprogram cohort (43.9%; OR: 9.70; P < .0001). The 6 month post-index hospitalization rate for the program cohort (14.7%) was significantly lower versus the nonprogram cohort after adjustments (22.5%; OR: 0.55; P = 0.0321). LIMITATIONS: The data for the program and nonprogram patients were from two different and independent data sources (healthcare claims and chart reviews, respectively). Results were based on a relatively small number of program LAI patients. CONCLUSION: Program patients treated with LAI antipsychotics had higher persistence rates and significantly lower adjusted hospitalization rates compared with nonprogram patients treated with OAs.

Evaluation of a comprehensive information and assistance program for patients with schizophrenia treated with long-acting injectable antipsychotics.

OBJECTIVE: While atypical long-acting injectable antipsychotics (LAIs) offer the potential for increased adherence, access to medication poses challenges that may hinder their use. Janssen Connect * *Janssen Connect is a registered trade name of Janssen Scientific Affairs, LLC, Titusville, NJ, USA. (JC), a comprehensive information and assistance program, was designed to help patients who received a Janssen LAI initiate and maintain treatment after their health care professional (HCP) determined that the medication was the most clinically appropriate option. We conducted a formative and impact evaluation on early medication adherence of patients enrolled in JC and prescribed paliperidone palmitate. METHODS: Using the program administrative files (December 2010-April 2014), 9354 patients whose HCP ordered paliperidone palmitate were included. Patient demographics, clinical characteristics, and request of JC program offerings were reported overall, and compared between patients requesting the injection center versus those who did not. Medication adherence based on the first 6 months of treatment while in the program and defined as achieving ≥80% proportion of days covered (PDC) was measured for patients receiving ≥2 paliperidone palmitate injections (n = 2659). Logistic models evaluated the association between requests for injection centers on medication adherence. RESULTS: Mean age of program enrollees was 40.6 (standard deviation = 13.9 years), 59.3% were men, and 42.5% were Medicare covered. While in the program, 79.9% did not experience a medication gap of ≥7 weeks and 87.0% achieved adherence. Injection center request was associated with medication adherence (adjusted odds ratio (aOR) ≤5 months: 0.03; 95% confidence interval (CI): 0.02-0.05; ≥6 months: aOR: 4.16; 95% CI: 2.72-6.36). LIMITATIONS: The data sources used were designed for program implementation and not for research purposes. CONCLUSIONS: The high percentage of patients requesting injection center support and medication shipment in addition to other insurance-related program offerings signals the need for and value of a comprehensive support program for patients seeking LAI therapy. Providing patients with the option of alternative and more conveniently located injection centers may help them start and maintain their treatment.

Cost effectiveness of paliperidone palmitate versus oral antipsychotics in patients with schizophrenia and a history of criminal justice involvement.

OBJECTIVE: Conduct a cost effectiveness analysis for the Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) trial. RESEARCH DESIGN AND METHODS: PRIDE was a 15 month, prospective, randomized, open-label study in which once monthly paliperidone palmitate significantly delayed the time to first treatment failure (healthcare or criminal justice system [HC/CJS] events) versus oral antipsychotics in recently incarcerated adults with schizophrenia. The present analysis used a state government perspective and HC/CJS event data that were collected on a resource use questionnaire (RUQ) every 3 months. MAIN OUTCOME MEASURES: Since cost information was not collected in the trial, cost estimates from published literature and an analysis of multistate Medicaid data for CJS and HC events, respectively, were applied to RUQ event data. Effectiveness and costs were adjusted to 456 days (trial duration). Incremental cost effectiveness was calculated as the adjusted cost difference divided by the adjusted effectiveness difference. RESULTS: Adjusted costs (in US dollars) in the paliperidone palmitate group (n = 198) and the oral antipsychotic group (n = 193), respectively, were: non-drug costs $22,331 and $25,027; drug costs $18,592 and $7833; and total costs $40,923 and $32,860. Adjusted effectiveness differences and corresponding incremental cost effectiveness per event avoided (in parentheses) for paliperidone palmitate versus oral antipsychotics were as follows: 0.33 fewer CJS events ($24,409), 0.13 fewer psychiatric hospitalizations ($60,484), 0.46 fewer psychiatric hospitalizations or CJS events combined ($17,391), and 0.30 fewer incarcerations ($26,754). CONCLUSIONS: Costs for HC/CJS events avoided offset 25% of the greater drug cost for the paliperidone palmitate versus oral antipsychotic treatment group in this vulnerable population. Use of a recall-dependent RUQ for event rates and cost estimates instead of actual costs are potential limitations and may make the results conservative from a state government perspective. Indirect costs are likely to be substantial for this population, but were not considered in the analysis.

Medicaid Eligibility and Time to Re-incarceration Among Previously Incarcerated Subjects With Schizophrenia.

Background: Many persons with severe mental illness qualify for Medicaid coverage. However, under federal law, states must either suspend or terminate eligibility once they are incarcerated. We hypothesize that prompt re-acquisition of Medicaid eligibility following release from incarceration lowers the risk of re-incarceration. Objective: To assess the relationship between Medicaid eligibility and risk of re-incarceration among previously incarcerated schizophrenia diagnosed subjects. Methods: Study subjects were selected between January 1, 2006 and September 30, 2011 from a single state Medicaid database that was combined with department of corrections data. Subjects were included if they had a schizophrenia diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD- 9-CM] code 295.xx), were between the ages of 18 and 62, and had been released from incarceration. Covariates included age, race, gender, marital status, and reason for incarceration. Time to Medicaid eligibility after release from incarceration, cumulative days of eligibility, and whether they were eligible on the re-incarceration date were evaluated in independent models. One and three-year Cox Regression models analyses (p<0.05) were used to evaluate the hazard for re-incarceration. Results: The 932 subjects were 26.5% white, 73.7% male and were, on average, 37.6 years old on their index date (i.e., incarceration release date). They were 73.5% single or divorced and 12.7% were incarcerated for a substance abuse violation. In the 1-year follow-up period, 110 subjects (11.8%) were re-incarcerated. In the 3-year follow-up period 209 (22.4%) were re-incarcerated. Age (in years) was the only significant predictor of re-incarceration for the 1-year models (hazard ratio [HR]=0.976; confidence interval [CI]=0.957, 0.994). Eligibility was a significant predictor in the 3-year follow-up models. A longer 'time to first eligibility' (HR=1.046; CI=1.017, 1.075 was associated with a greater hazard for re-incarceration. Being eligible at the time of re-incarceration (HR=0.659; CI=0.498, 0.870) was associated with a lower hazard, and the cumulative number of months of eligibility (HR=0.978; CI=0.958, 0.997) and age were associated with a lower hazard for re-incarceration (HR=0.986; CI=0.973, 0.999). Conclusions: Access to Medicaid health services post-release may reduce the risk of re-incarceration.

Complexity of pain management among patients with nociceptive or neuropathic neck, back, or osteoarthritis diagnoses.

BACKGROUND: Approaches to pain management are diverse, requiring prescribers to evaluate an array of clinical issues and potential solutions. In addition to the difficult task of selecting a treatment option, pain treatment may be further complicated by multiple prescribers, multiple medications, and multiple mechanisms of pain origination. OBJECTIVE: To describe patient demographics (e.g., age, gender); comorbidities; office visits (e.g., physician, chiropractor, physical therapy, psychiatry, allergist); number of different prescribers overall prescription use; pain medications as classified by the World Health Organization's (WHO) pain ladder; adjuvant medications; nonpharmacologic procedures; and potential drug interactions in a broad sample of patients with nociceptive or neuropathic neck or back diagnoses, or osteoarthritis diagnoses, in a commercial population. METHODS: This claims-data analysis used a cross-sectional cohort comparison with a fixed 2-year observation period from September 1, 2006, to August 31, 2008, for patients in the PharMetrics national managed care database. The assigned cohorts were neuropathic-related neck/back diagnoses (NEURO); neuropathic and nociceptive neck/back diagnoses (NEURO/NOCI); nociceptive neck/back diagnoses without a neuropathic-related diagnosis (NOCI); and only osteoarthritis (OA) diagnoses. All analyses were conducted by cohort. The analysis included the following patient-descriptive variables: patient demographics, comorbidities, office visits, most frequent medical providers and number of different prescribers, all medications, pain medications as classified by the WHO pain ladder, adjuvant medications, adjuvant procedures and potential drug interactions. The goal for selecting these variables was to describe a range of data that might provide insight into the complexity of pain management decisions faced by clinicians. RESULTS: The study included 85,014 patients, classified as NEURO (n = 2,375), NEURO/NOCI (n = 37,019), NOCI (n = 39,496), and OA (n = 6,124). The most frequently occurring comorbidities (observed in > 40% of patients) included cardiovascular and neuropathic pain conditions. Considering all types of medication claims observed among all cohorts, the overall mean prescription claim count for the 2-year observation period was 57.9 claims (standard deviation 56.2). Weak opioids (WHO pain relief ladder rung 2) accounted for the majority of pain medication claims across all cohorts. Across cohorts, 25.7% of patients had 10 or more days of overlapping drug availability (for inducers or inhibitors of the cytochrome P450 system concomitantly), a measure of potential for drug interactions. CONCLUSIONS: Choosing the appropriate pain treatment involves assessing currently used medications for existing illnesses and deciding on the appropriate types of pain medications. However, potentially serious drug-drug interactions are a consequence of multiple drug use, and such a potential requires thoughtful consideration by those involved in patient care.

Immediate-release tapentadol or oxycodone for treatment of acute postoperative pain after elective arthroscopic shoulder surgery: a randomized, phase IIIb study.

OBJECTIVE: Arthroscopic shoulder surgery can result in substantial postoperative pain. This study evaluated the efficacy and safety of tapentadol immediate release (IR) or oxycodone IR in this setting for the treatment of acute pain. DESIGN: Subjects received tapentadol IR 50 or 100 mg or oxycodone IR 5 or 10 mg every 4-6 hours as needed for pain up to 7 days after arthroscopic shoulder surgery. Twice daily, subjects recorded pain intensity from 0 (no pain) to 10 (pain as bad as you can imagine) and pain relief from 0 (none) to 5 (complete). Final assessments included patient and clinician global impression of change and subject satisfaction with treatment. The primary efficacy endpoint was the sum of pain intensity differences (SPID) over 3 days. RESULTS: Of 378 subjects (192 tapentadol IR, 186 oxycodone IR) who took study medication, 312 (158 tapentadol IR, 154 oxycodone IR) had pain intensity ≥4 before the first dose and were evaluated for efficacy. Mean SPID scores over 3 days were 32.1 and 41.1 in the tapentadol IR and oxycodone IR groups, respectively (least-squares mean difference [95% confidence interval], 9.0 [-18.9, 36.9]; p = 0.527). Secondary analyses of pain intensity, pain relief, and subject satisfaction were similar between groups. Subjects and clinicians reported significantly better global impression of change for tapentadol IR. Adverse events were consistent with established safety profiles for IR opioids. CONCLUSIONS: Tapentadol IR and oxycodone IR had similar efficacy for pain after arthroscopic shoulder surgery, but subjects and clinicians reported greater overall improvement with tapentadol IR.

Physician management of moderate-to-severe acute pain: results from the Physicians Partnering Against Pain (P³) study.

OBJECTIVE: To evaluate differences among physician specialties in the management of acute pain including prescribing practices and management of opioid-related side effects. DESIGN AND PARTICIPANTS: The Physicians Partnering Against Pain (P³) survey was a nationwide study of US physicians and their patients with severe to moderate acute pain (<3 months). MAIN MEASURES: Physicians were surveyed about volume of patients with moderate-to-severe acute pain in their practice, frequency of prescribing opioid analgesics, percentage of these patients returning for a follow-up visit after treatment, reasons patients discontinue treatment, frequency of recommending or prescribing treatment for opioid-related gastrointestinal (GI) side effects, and frequency of patients taking opioid analgesics that take additional treatments to manage GI side effects. RESULTS: The 5,982 participating physicians represented primary care physicians (PCPs; 52 percent), pain specialists (25 percent), and other specialists (23 percent). PCPs and other specialists were less likely than pain specialists to prescribe opioid analgesics to patients (25.8 percent, 29.5 percent, and 44.8 percent, respectively). The vast majority of pain specialists (78 percent) also indicated that more than three quarters of their patients returned for a follow-up visit compared with only 40 percent of PCPs and 65 percent of other specialists. When ranking the reasons why they think patients discontinue opioid analgesics, pain specialists ranked unacceptable side effects higher than PCPs and other specialists. PCPs and pain specialists were more likely than other specialists to recommend or prescribe treatments to manage opioid-related side effects, such as nausea, vomiting, and constipation (38.3 percent, 38.5 percent, and 23.1 percent, respectively). CONCLUSION: The P(3) Study confirms the challenge of pain management while balancing tolerability of opioid treatments from the physician perspective.

Analgesic treatment for moderate-to-severe acute pain in the United States: patients' perspectives in the Physicians Partnering Against Pain (P3) survey.

OBJECTIVES: To evaluate patients' perceptions of the adequacy of analgesia for moderate-to-severe acute pain and the influence of opioid-related side effects in outpatient pain management. SETTING: The Physicians Partnering Against Pain (P3) survey of analgesic treatment for moderate-to-severe acute pain in the United States. PATIENTS: Adults with moderate-to-severe acute pain at their first analgesic followup visit. MAIN OUTCOME MEASURES: Analgesic level was determined from the World Health Organization'spain ladder (0 = none; 1 = nonopioid; 2 = weak opioid; 3 = strong opioid). Pain intensity was derived from numeric rating scale (NRS) scores (0 = none [NRS = 0]; 1 = mild [NRS = 1-3]; 2 = moderate [NRS = 4-7]; 3 = severe [NRS = 8-10). Pain management index scores were calculated as the analgesic level minus the pain intensity. Opioid recipients responded to questions on the P3 survey regarding side effects and their management. RESULTS: Of the 50,869 patients with complete data for analysis, 22,267 (44 percent) had received potentially inadequate analgesia, including 43, 46, and 52 percent of patients aged < 65, 65-74, and > or = 75 years, respectively. Of the 39,6 75 patients treated with an opioid, 10,925 (28 percent) experienced at least one gastrointestinal side effect (nausea, vomiting or constipation). Many of these patients stopped taking the medication (13 percent) or reduced their dose (16 percent) to manage gastrointestinal side effects. CONCLUSIONS: In the P3 study, one of the largest outpatient surveys conducted in pain management, moderate-to-severe acute pain continued to be widely undertreated in outpatient settings in the United States, particularly among older patients. Opioids with improved tolerability profiles might help to alleviate this undertreatment of moderate-to-severe acute pain.

Adverse event profile of tramadol in recent clinical studies of chronic osteoarthritis pain.

OBJECTIVE: To review the safety profile of tramadol hydrochloride (tramadol) in the treatment of chronic osteoarthritis pain, with specific reference to the incidence of adverse events (AEs) reported in large clinical trials. METHODS: An extensive review of published clinical trials with tramadol was conducted, using literature searches in MEDLINE and EMBASE (since 1997) and the key search terms: tramadol, immediate-release (IR), extended-release (ER), sustained-release (SR), chronic pain, and osteoarthritis. Studies were included based on appropriate study design, appropriately reported safety data, and chronic osteoarthritis as a pain condition. Secondary analyses of previously published pain studies were excluded. RESULTS: Fifteen studies met the inclusion criteria. The most common AEs reported across all tramadol formulations were nausea, dizziness, constipation, vomiting, somnolence, and headache. Most AEs were mild to moderate in severity and occurred more commonly during initial treatment than during maintenance treatment. Differences in the rates of selected gastrointestinal and central nervous system AEs were seen between long-acting and immediate-release tramadol formulations, both within individual studies and across all studies. AEs appeared to be dose-dependent in fixed-dose studies. CONCLUSIONS: This review provides a robust base for descriptive assessment of AEs associated with long-acting tramadol formulations. Although the actions of different tramadol formulations are biologically similar, differences in pharmacokinetics, drug-release patterns, and availability may influence the incidence of AEs associated with tramadol. Because of the limitations of a qualitative safety analysis across studies with different populations and study designs, any observed differences should be interpreted with caution, but these differences may help educate healthcare providers about tramadol treatment in patients with chronic osteoarthritis pain and help them select the optimal dose for specific patients.