At baseline patients treated with esketamine have higher burden of disease than other patients with treatment resistant depression: Learnings from a population based study.

INTRODUCTION: It is critical to assess who is being treated with a new marketed drug like esketamine to understand how it is used in the real-world setting and the effects of the medication. METHODS: Retrospective analysis using two large U.S. health care databases that included commercially insured and Medicaid patients. Patients treated with esketamine were identified and their baseline characteristics described and compared with the baseline characteristics of patients with treatment resistant depression (TRD) and with patients undergoing transcranial magnetic stimulation (TMS). To quantify the differences, standardized mean differences were calculated. RESULTS: In the commercially insured database, 418 patients were treated with esketamine and 830,047 patients were in the TRD group. Large differences in baseline characteristics were observed. Patients in the esketamine group were more likely to have severe depression, suicidal thoughts, and prior treatments with TMS or electroconvulsive therapy than the TRD control group. Patients in the esketamine group had more comorbid psychiatric conditions (anxiety disorder, posttraumatic stress disorders, substance use disorders) and higher exposure to antipsychotics, antiepileptics, hypnotics and sedatives. In terms of general health, patients in the esketamine group had many more outpatient visits, were more likely to have chronic pain and higher Charlson comorbidity scores, a predicator of mortality. Results were similar for both the Medicaid and TMS populations. CONCLUSION: Patients treated with esketamine have a higher burden of disease than other patients with TRD. In any real-world comparative effectiveness or safety study these differences need to be understood and accounted for to produce valid results.

Individuals who develop drug-resistant epilepsy within a year after initial diagnosis have higher burden of mental and physical diseases one-year prior to epilepsy diagnosis as compared to those whose seizures were controlled during the same interval.

INTRODUCTION: Epilepsy is a neurological disease characterized by recurrent, unprovoked seizures and its impact on biological, cognitive, psychological, and social outcomes. An unmet need for finding effective treatment options exists. Identifying medical diagnoses present prior to a diagnosis of epilepsy is an important step in increasing our understanding of how people with epilepsy may respond to therapy, help guide clinicians in managing associated comorbid conditions, and inform future research. METHODS: A population-based retrospective comparative cohort study was conducted using administrative claims data to explore differences in medical diagnoses prior to an initial diagnosis of epilepsy between patients with and without drug-resistant epilepsy (DRE) identified within one-year post diagnosis by evaluating standardized mean differences between the groups. RESULTS: A total of 205,183 patients with newly diagnosed epilepsy were identified. Of those, 4.1% (n = 8340) were considered drug resistant one-year post diagnosis. Pain and mood disorders were the common physical and psychiatric diagnoses in both cohorts. Differences between the newly diagnosed epilepsy and DRE cohorts were observed. Patients in the DRE cohort were younger, had more encounters with the healthcare system, and higher burden of disease for both physical (e.g., headache, neuropathy, muscular-skeletal disorders, and traumatic brain injury) and psychiatric diagnoses (e.g., depression, anxiety, bipolar disorder, suicidal thoughts, drug dependency, and sleep disorders). CONCLUSION: Physical and psychiatric diagnoses are common one year prior to first diagnosis of epilepsy in administrative claims data. Compared to patients without DRE, those who develop DRE within one-year post initial diagnosis demonstrated a higher burden of disease.

Treatment patterns of patients diagnosed with major depressive disorder and suicidal ideation or attempt: a U.S. population-based study utilizing real-world data.

BACKGROUND: There is a knowledge gap regarding the treatment patterns of patients with major depressive disorder (MDD) who experience suicidal ideation or a suicide attempt (SI/SA). METHODS: Patients with SI/SA were identified from a large US-based claims database covering 84 million lives, during 1/1/2014-3/31/2020. Patients with MDD were indexed at their first diagnosis for SI/SA and followed up to 365 days. Treatment patterns were captured at the class level and included procedures of electroconvulsive therapy and transcranial magnetic stimulation, and pharmacotherapy including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, antipsychotics, psychostimulants, and lithium. RESULTS: There were 42,204 MDD + SI/SA patients identified. In the year prior to the index event > 40% of individuals received an SSRI and more than one-third received an anxiolytic. Within 1 year following, 84.4% received ≥1 of the treatments of interest. Of those, 70.2% went on to a subsequent class-based regimen, 46.3% received a third, and 28.1% received ≥4. More than three-quarters of patients received multiple treatment classes simultaneously. SSRIs were the most common treatments during follow-up (61.9%), followed by other antidepressants (51.3%), anxiolytics (50.8%) and anticonvulsants (43.6%). CONCLUSIONS: There was a large amount of variability and polypharmacy in the treatments received by MDD patients with SI/SA, and is much more complex than what has been previously observed in the general MDD population. Within one-year, many patients received four or more unique class-based regimens and most patients received treatments from multiple classes simultaneously, indicating the high unmet medical need and therapy refractoriness of this patient population.

Treatment patterns and comorbid burden of patients newly diagnosed with multiple sclerosis in the United States.

BACKGROUND: The treatment landscape for multiple sclerosis (MS) is quickly evolving. Understanding real-world treatment patterns of patients is necessary to identifying potential gaps in care. METHODS: Patients with incident MS were identified from a large national claims database during 1/1/2014-6/30/2019. Patients had ≥2 diagnoses for MS or an inpatient hospitalization with a primary diagnosis of MS. Patients were required to have enrollment in the database ≥1 year prior to and ≥ 1 year following their first MS diagnosis. Treatment sequences were captured for all available disease modifying therapies (DMTs) during all available follow-up. Presence of comorbid conditions were captured during the one year prior to and following (and including) the index date; absolute change in prevalence from the pre- to post-index periods was calculated. RESULTS: We identified 5691 patients with incident MS. Common comorbidities included physical symptoms (e.g., pain, weakness, fatigue), mental health conditions (anxiety, depression), and cardiovascular/metabolic conditions (hypertension, hyperlipidemia, diabetes, obesity). Just 1994 (35.0%) of patients received a DMT at any time during follow-up. Of those receiving a DMT, 28.2% went on to receive a second line of therapy, 5.8% received a third, and just 0.9% went on to a fourth line. Use of more than one DMT concomitantly occurred in just 1.8% of all treated patients. Glatiramer and dimethyl fumarate were by far the most common first-line treatments received accounting for nearly 62% of patients receiving a DMT. CONCLUSION: Approximately two-thirds of patients newly diagnosed with MS did not receive a DMT and the disease is accompanied by a significant comorbid burden.

Oral Opioid Prescribing Trends in the United States, 2002-2018.

OBJECTIVE: To conduct a retrospective analysis of sequential cross-sectional data of opioid prescribing practices in patients with no prior history of opioid use. METHODS: Individuals filling an oral opioid prescription who had 1 year of prior observation were identified from four different administrative claims databases for the period between January 1, 2002, and December 31, 2018: IBM MarketScan® Commercial Database (CCAE), Multi-State Medicaid Database (MDCD), Medicare Supplemental Database (MDCR), and Optum©â€¯De-Identified Clinformatics® Data Mart Database. Outcomes included incidence of new opioid use and characteristics of patients' first opioid prescription, including dispensed morphine milligram equivalent (MME) per day, total MME dispensed, total MME ≥300, and days' supply of prescription for ≤3 or ≥30 days. RESULTS: There were 40,600,696 new opioid users identified. The incidence of new opioid use in the past 17 years ranged from 6% to 11% within the two commercially insured databases. Incidence decreased over time in MDCD and was consistently higher in MDCR. Total MME dispensed decreased in MDCD and increased in CCAE, with no major changes in the other databases. The proportion of patients receiving ≥30-day prescriptions decreased and the proportion of patients receiving ≤3-day prescriptions increased in MDCD, while ≥30-day prescriptions in the Optum database dramatically increased (low of 3.0% in 2003 to peak of 16.9% in 2017). CONCLUSIONS: Opioid prescribing practices varied across different populations of insured individuals during the past 17 years. The most substantial changes in opioid prescriptions over time have occurred in MDCD, with reductions in use across multiple metrics.

Frequency of Early Refills for Opioids in the United States.

OBJECTIVE: Refilling an opioid prescription early is an important risk factor of prescription opioid abuse and misuse; we aimed to understand the scope of this behavior. This study was conducted to quantify the prevalence and distribution of early refills among patients prescribed opioids. METHODS: We conducted a retrospective cohort study utilizing dispensed prescription records. Patients filling one or more prescription opioids were identified and followed for one year. Early refills were defined as having a second prescription filled ≥15% early relative to the days' supply of the previous prescription for the same opioid (according to the National Drug Code [NDC]). The distribution of the number of early refills and patient characteristics were assessed. RESULTS: A total of 60.6 million patients met the study criteria; 28.8% had two or more opioid prescriptions for the same opioid during follow-up. Less than 3% of all patients receiving an opioid had an early refill. Approximately 10% of those with two or more opioid prescriptions for the same drug had an early refill. For patients with multiple fills (N = 1.5 million with extended-release long-acting [ER/LA] opioids; N = 17.1 million with immediate-release short-acting [IR/SA] opioids), early refills were more common among patients with an ER/LA opioid (18.5%) compared with an IR/SA opioid (8.7%). Three-quarters of patients with an early refill had only one (70.9% and 78.4% for ER/LA and IR/SA, respectively). CONCLUSION: Refilling an opioid prescription with the same opioid early is an infrequent behavior within all opioid users, but more common in ER/LA users. Patients who refilled early tended to do so just once.

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

OBJECTIVE: To assess changes in mortality rates in extended-release and long-acting (ER/LA) opioid analgesics after the implementation of the Risk Evaluation and Mitigation Strategy (REMS). SETTING: All drug poisoning deaths in three states: Florida, Oregon, and Washington. Data were obtained through state vital records offices and the Researched Abuse, Diversion and Addiction-Related Surveillance System Medical Examiner Program. METHODS: Using cause-of-death literal text from death certificates, individual opioid active pharmaceutical ingredients (APIs) involved in each death were identified using rules-based natural language processing. Population-adjusted and prescriptions dispensed-adjusted mortality rates were calculated for all ER/LA opioid analgesic and individual opioid APIs. Rates before and after implementation of the REMS were compared. Rate changes were compared with rates from two APIs with little or no inclusion in the REMS: benzodiazepines and hydrocodone. RESULTS: The mean ER/LA opioid analgesic population-adjusted mortality rate significantly decreased in all three states (FL: P = 0.003; OR: P = 0.003; WA: P < 0.001). Mortality rates for benzodiazepines and hydrocodone also decreased and were not statistically different. Significant heterogeneity in mortality rates of individual opioids was observed between the three states. When adjusted for prescription volume, the ER/LA opioid analgesic mortality rate decreased in all three states, but was significant only for Washington (P < 0.001). CONCLUSIONS: The population-adjusted mortality rate of ER/LA opioid analgesics has decreased in three states. Notably, the contributions to mortality rates by individual opioid analgesics were not uniform across the three states in this study. However, these changes were not generally distinct from changes in mortality rates where comparator substances were involved.

Treatment patterns and sequences of pharmacotherapy for patients diagnosed with depression in the United States: 2014 through 2019.

BACKGROUND: Understanding how patients are treated in the real-world is vital to identifying potential gaps in care. We describe the current pharmacologic treatment patterns for the treatment of depression. METHODS: Patients with depression were identified from four large national claims databases during 1/1/2014-1/31/2019. Patients had ≥2 diagnoses for depression or an inpatient hospitalization with a diagnosis of depression. Patients were required to have enrollment in the database ≥1 year prior to and 3 years following their first depression diagnosis. Treatment patterns were captured at the class level and included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, and antipsychotics. Treatment patterns were captured during all available follow-up. RESULTS: We identified 269,668 patients diagnosed with depression. The proportion not receiving any pharmacological treatment during follow-up ranged from 29 to 52%. Of the treated, approximately half received ≥2 different classes of therapy, a quarter received ≥3 classes and more than 10% received 4 or more. SSRIs were the most common first-line treatment; however, many patients received an anxiolytic, hypnotic/sedative, or antipsychotic prior to any antidepressive treatment. Treatment with a combination of classes ranged from approximately 20% of first-line therapies to 40% of fourth-line. CONCLUSIONS: Many patients diagnosed with depression go untreated and many others receive a non-antidepressant medication class as their first treatment. More than half of patients received more than one type of treatment class during the study follow up, suggesting that the first treatment received may not be optimal for most patients.

Treatment resistant depression in women with peripartum depression.

BACKGROUND: Peripartum depression is a leading cause of disease burden for women and yet there is little evidence as to how often peripartum depression does not respond to treatment and becomes treatment resistant depression. We sought to determine the incidence of treatment resistant depression (TRD) in women with peripartum depression. METHODS: Population based retrospective cohort study using a large US claims database. Peripartum depression was defined as having a depression diagnosis during pregnancy or up to 6 months after the end of pregnancy. We included women with prevalent or incident depression. The outcome was the development of TRD within 1 year after the diagnosis of peripartum depression. TRD was defined as having 3 distinct antidepressants or 1 antidepressant and 1 antipsychotic in 1 year. Women with peripartum depression may not be exposed to pharmacological treatments early in pregnancy, therefore we created two groups: 1. women with peripartum depression, and 2. women with peripartum depression diagnosed 3 months before a live birth delivery or within 6 months after that delivery. RESULTS: There were 3,207,684 pregnant women, of whom 2.5% had peripartum depression. Of these women half had incident depression during pregnancy. Five percent of women with peripartum depression developed TRD within 1 year of the depression diagnosis. The risk of developing TRD was 50% higher in women with prevalent depression than in women with incident peripartum depression (P < 0.0001). Results were similar in women with peripartum depression diagnosed later in their pregnancy. Women who went on to develop TRD had more substance use disorders, anxiety, insomnia and painful conditions. CONCLUSIONS: TRD occurs in approximately 5% of women with peripartum depression. The risk of TRD is higher in pregnant women with a history of depression. Women who went on to develop TRD had more psychiatric comorbidities and painful conditions than women who did not.

Finding factors that predict treatment-resistant depression: Results of a cohort study.

BACKGROUND: Treatment for depressive disorders often requires subsequent interventions. Patients who do not respond to antidepressants have treatment-resistant depression (TRD). Predicting who will develop TRD may help healthcare providers make more effective treatment decisions. We sought to identify factors that predict TRD in a real-world setting using claims databases. METHODS: A retrospective cohort study was conducted in a US claims database of adult subjects with newly diagnosed and treated depression with no mania, dementia, and psychosis. The index date was the date of antidepressant dispensing. The outcome was TRD, defined as having at least three distinct antidepressants or one antidepressant and one antipsychotic within 1 year after the index date. Predictors were age, gender, medical conditions, medications, and procedures 1 year before the index date. RESULTS: Of 230,801 included patients, 10.4% developed TRD within 1 year. TRD patients at baseline were younger; 10.87% were between 18 and 19 years old versus 7.64% in the no-TRD group, risk ratio (RR) = 1.42 (95% confidence interval [CI] 1.37-1.48). TRD patients were more likely to have an anxiety disorder at baseline than non-TRD patients, RR = 1.38 (95% CI 1.35-1.14). At 3.68, fatigue had the highest RR (95% CI 3.18-4.25). TRD patients had substance use disorders, psychiatric conditions, insomnia, and pain more often at baseline than non-TRD patients. CONCLUSION: Ten percent of subjects newly diagnosed and treated for depression developed TRD within a year. They were younger and suffered more frequently from fatigue, substance use disorders, anxiety, psychiatric conditions, insomnia, and pain than non-TRD patients.

Finding treatment-resistant depression in real-world data: How a data-driven approach compares with expert-based heuristics.

BACKGROUND: Depression that does not respond to antidepressants is treatment-resistant depression (TRD). TRD definitions include assessments of treatment response, dose and duration, and implementing these definitions in claims databases can be challenging. We built a data-driven TRD definition and evaluated its performance. METHODS: We included adults with depression, ≥1 antidepressant, and no diagnosis of mania, dementia, or psychosis. Subjects were stratified into those with and without proxy for TRD. Proxies for TRD were electroconvulsive therapy, deep brain, or vagus nerve stimulation. The index date for subjects with proxy for TRD was the procedure date, and for subjects without, the date of a randomly selected visit. We used three databases. We fit decision tree predictive models. We included number of distinct antidepressants, with and without adequate doses and duration, number of antipsychotics and psychotherapies, and expert-based definitions, 3, 6, and 12 months before index date. To assess performance, we calculated area under the curve (AUC) and transportability. RESULTS: We analyzed 33,336 subjects with no proxy for TRD, and 3,566 with the proxy. Number of antidepressants and antipsychotics were selected in all periods. The best model was at 12 months with an AUC = 0.81. The rule transported well and states that a subject with ≥1 antipsychotic or ≥3 antidepressants in the last year has TRD. Applying this rule, 15.8% of subjects treated for depression had TRD. CONCLUSION: The definition that best discriminates between subjects with and without TRD considers number of distinct antidepressants (≥3) or antipsychotics (≥1) in the last year.

Microbiome-Gut-Brain Axis: Probiotics and Their Association With Depression.

To assess the association of probiotics with depression, a large population-based cross-sectional study was conducted. National Health and Nutrition Examination Survey adult participants from 2005 through 2012 were included. Exposure was defined as having consumed any probiotic food or supplement on any of the interview days. Subjects were classified as depressed if Patient Health Questionnaire scores were ≥10. Of the 18,019 subjects included, 14.11% consumed probiotics. Unadjusted analysis suggested that subjects who consumed probiotics had lower odds of depression (OR=0.58, 95% CI=0.45-0.75). After adjustment for characteristics associated with depression and probiotic exposure, the effect was attenuated (OR=0.82, 95% CI=0.61-1.1) and no longer significant. Use of probiotics is not associated with lower rates of depression in this national sample.

Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

PURPOSE: An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. METHODS: Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RESULTS: RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. CONCLUSIONS: While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends.

Association of flossing/inter-dental cleaning and periodontitis in adults.

AIM: Assess the association of flossing with periodontitis. MATERIALS AND METHODS: This was a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) years 2011-2014. We used three categories of flossing: 0-1, 2-4 and ≥5 days in the past week and the CDC definition of periodontitis. We calculated odds ratios controlling for age, gender, smoking, drinking, income and dentist visits. RESULTS: A total of 6939 adult subjects were included, 35% flossed ≤1 time a week, and 40% had periodontitis. After adjustment, the odds of periodontitis were 17% lower for subjects who flossed >1 time a week than for subjects who flossed less often (odds ratio=0.83, 95% CI 0.72-0.97). A dose response was not observed. Men were twice as likely as women to have periodontitis. Younger subjects, non-smokers and subjects with the highest incomes had lower odds of having periodontitis. CONCLUSIONS: Flossing was associated with a modestly lower prevalence of periodontitis. Older age, being male, smoking, low income and less frequent dental visits were associated with a higher prevalence of periodontitis. Flossing 2-4 days a week could be as beneficial as flossing more frequently. This is a cross-sectional study so a causal relation between flossing and periodontitis cannot be established.

ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes.

Objective: Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. Methods: The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. Results and Conclusions: The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids.

Doctor shopping for medications used in the treatment of attention deficit hyperactivity disorder: shoppers often pay in cash and cross state lines.

BACKGROUND: Doctor shopping, defined by filling overlapping prescriptions from more than one prescriber at more than two pharmacies, is a way to obtain scheduled medications for diversion or abuse. Little is known about how far attention deficit hyperactivity disorder (ADHD) medication shoppers travel, how often they cross state lines to fill their ADHD prescriptions and how often they pay for their medication in cash, i.e. entirely out of pocket. OBJECTIVE: We sought to describe the pattern of doctor shopping for ADHD medications: how far shoppers travel, how often they cross state lines to fill their prescriptions, and how often they pay in cash. METHODS: Retrospective cohort study using LRx, a large US retail prescription database. We included subjects with any ADHD medication dispensed between 2011 and 2012. Subjects were followed for 18 months. RESULTS: Of a total of 4 402 464 subjects exposed to ADHD medications, 0.4% developed shopping behavior. Women were more likely to become shoppers. Shoppers travelled a median of 91.9 miles and non-shoppers 0.2 miles to fill their ADHD prescriptions. Almost 28% of the shoppers filled prescriptions in >1 state compared with 4.3% of non-shoppers. Of the shoppers, 27.3% paid at least one prescription in cash compared to 14.4% of the non-shoppers. CONCLUSIONS: Shoppers travelled larger distances, visited more states and paid in cash for ADHD medications more often than non-shoppers. Data sharing among prescriptions monitoring programs can improve their effectiveness and drug utilization studies should take account of cash purchases.

Pain qualities and satisfaction with therapy: a survey of subjects with neuropathic pain.

OBJECTIVES: Pain qualities may reflect neurobiological mechanisms and guide therapy. The objective was to assess whether pain qualities were associated with satisfaction with pain relief in subjects with neuropathic pain. METHODS: Subjects responded to a web survey that included current pain qualities, type of medications, and satisfaction with pain relief. RESULTS: A total of 1,502 subjects, primarily with diabetic neuropathy, completed the survey and were grouped into six clusters based on their pain qualities. Subjects in the Broadest spectrum endorsed all pain types (paroxysmal, throbbing, paresthesias, evoked pain, and numbness). Subjects in the Broad spectrum endorsed all types of pain, but to a lesser degree. Subjects in the Sharp paroxysmal and paresthesias endorsed mainly stabbing-like pain, subjects in the throbbing dull pain endorsed throbbing and pressure, subjects in the numbness endorsed mainly numbness, and subjects in the least affected endorsed few symptoms. The degree of satisfaction in each cluster varied with the type of medication. Two clusters were dissatisfied with antidepressants: subjects with paroxysmal pain and paresthesias (odds ratio [OR] = 0.38; 95% confidence interval [CI], 0.19-0.74) and subjects with the broadest spectrum of symptoms (OR = 0.63; 95% CI, 0.41-0.97). Two clusters were dissatisfied with opioids: subjects with throbbing and dull pain (OR = 0.44; 95% CI, 0.26-0.75) and subjects with numbness (OR = 0.48; 95% CI, 0.23-0.99). DISCUSSION: Pain qualities may help guide pain therapy and permit individualization of therapy.

From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results.

BACKGROUND: The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses. PURPOSE: To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis. METHODS: Sherlock(®) identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert. CONCLUSIONS: Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.

Suicide-specific mortality among patients with treatment-resistant major depressive disorder, major depressive disorder with prior suicidal ideation or suicide attempts, or major depressive disorder alone.

BACKGROUND: The impact of treatment-resistant depression (TRD) or prior suicidal ideation/suicide attempt (SI/SA) on mortality by suicide among patients with major depressive disorder (MDD) is not well known. This retrospective, observational, descriptive cohort study characterized real-world rates of suicide-specific mortality among patients with MDD with or without TRD or SI/SA. METHODS: Adult patients with MDD among commercially insured and Medicare enrollees in Optum Research Database were included and assigned to three cohorts: those with treatment-resistant MDD (TRD), those with MDD and SI/SA (MDD+SI/SA), and those with MDD without TRD or SI/SA (MDD alone). Suicide-specific mortality was obtained from the National Death Index. The effects of demographic characteristics and SI/SA in the year prior to the end of observation on suicide-specific mortality were assessed. RESULTS: For the 139,753 TRD, 85,602 MDD+SI/SA, and 572,098 MDD alone cohort patients, mean age ranged from 55 to 59 years and the majority were female. At baseline, anxiety disorders were present in 53.92%, 44.11%, and 21.72% of patients with TRD, MDD+SI/SA, and MDD alone, respectively. Suicide-mortality rates in the three cohorts were 0.14/100 person-years for TRD, 0.27/100 person-years for MDD+SI/SA, and 0.04/100 person-years for MDD alone. SI/SA during the year prior to the end of observation, younger age, and male sex were associated with increased suicide risk. CONCLUSIONS: Patients with TRD and MDD+SI/SA have a heightened risk of mortality by suicide compared with patients with MDD alone. Suicide rates were higher in patients with recent history versus older or no history of SI/SA, men versus women, and those of young age versus older age.