A Retrospective Matched Comparison Study of Prolonged Seizures in ECT.

OBJECTIVE: This study assessed the incidence of and risk factors for prolonged seizures (>180 sec) in electroconvulsive therapy (ECT). METHOD: In 611 adult patients undergoing 6697 ECT treatments administered over a 2.5-year study period, 29 individuals experienced 42 prolonged seizures. A comparison sample (n = 29) was matched on sex, age, and treatment, and compared on psychiatric and medical diagnoses, as well as current medications. To examine the association between the characteristics and prolonged seizure, conditional logistic regression models or exact McNemar tests were conducted. RESULTS: Prolonged seizures occurred on average in 1 of every 167 treatments. No specific psychiatric disorders or medical conditions were associated with the prolonged seizure group. Antipsychotic drugs were used in a higher proportion of the comparison group than in the prolonged seizure group, suggesting a protective effect. Atropine was used in a lower proportion of the long seizure group than in the comparison group. No untoward sequelae occurred, and no progression to status epilepticus was observed. CONCLUSIONS: Prolonged seizures appear to be an uncommon complication of ECT in adults. The characteristics examined in this study suggest limited association of psychotropic medications with prolonged seizures. Treatment of prolonged seizures was straightforward. Prolonged seizures had no impact on the course of treatment. Further exploration of prolonged seizures would enhance the generalizability of the findings from this single site study.

Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn's disease and ulcerative colitis in the United States.

BACKGROUND: The purpose of this analysis was to assess the frequency of inadequate response over 1 year from advanced therapy initiation among patients with Crohn's disease (CD) or ulcerative colitis (UC) in the United States using a claims-based algorithm. Factors associated with inadequate response were also analyzed. METHODS: This study utilized claims data of adult patients from the HealthCore Integrated Research Database (HIRD®) from January 01, 2016 to August 31, 2019. Advanced therapies used in this study were tumor necrosis factor inhibitors (TNFi) and non-TNFi biologics. Inadequate response to an advanced therapy was identified using a claims-based algorithm. The inadequate response criteria included adherence, switching to/added a new treatment, addition of a new conventional synthetic immunomodulator or conventional disease-modifying drugs, increase in dose/frequency of advanced therapy initiation, and use of a new pain medication, or surgery. Factors influencing inadequate responders were assessed using multivariable logistic regression. RESULTS: A total of 2437 patients with CD and 1692 patients with UC were included in this analysis. In patients with CD (mean age: 41 years; female: 53%), 81% had initiated TNFi, and 62% had inadequate response. In patients with UC (mean age: 42 years; female: 48%), 78% had initiated a TNFi, and 63% had an inadequate response. In both patients with CD and UC, inadequate response was associated with low adherence (CD: 41%; UC: 42%). Inadequate responders were more likely to be prescribed a TNFi (for CD: odds ratio [OR] = 1.94; p < 0.001; for UC: OR = 2.76; p < 0.0001). CONCLUSION: More than 60% of patients with CD or UC had an inadequate response to their index advanced therapy within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD and UC appears useful to classify inadequate responders in health plan claims data.

Medication use among patients with Crohn's disease or ulcerative colitis before and after the initiation of advanced therapy.

BACKGROUND: Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC. METHODS: This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database (HIRD®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test. RESULTS: Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, P < 0.001 in CD; 91.4% vs. 74.3%, P < 0.001 in UC), opioids (49.4% vs. 41.5%, P = 0.004 in CD; 40.8% vs. 36.5%, P = 0.194 in UC), and NSAIDs (23.1% vs. 15.0%, P < 0.001 in CD; 20.9% vs. 15.8%, P = 0.035 in UC), while the use of neuromodulators significantly increased (29.3% vs. 33.7%, P = 0.007 in CD; 29.5% vs. 35.7%; P = 0.006 in UC). CONCLUSIONS: The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies.

Psychotropic Medication Effects on Seizure Threshold and Seizure Duration During Electroconvulsive Therapy Stimulus Titration.

OBJECTIVES: Decisions about psychotropic medication administration before electroconvulsive therapy (ECT) are central to management of a very psychiatrically ill patient population. Given that many psychotropic medications are thought to either promote or prevent seizures, there is ongoing concern about concurrent psychotropic medication and ECT administration. This study examined the effect of psychotropic medications on seizure threshold and duration during ECT stimulus titration. METHODS: The study sample consisted of 550 patients receiving ECT stimulus titration at a single site during a 27-month period. Systematic chart review provided clinical data, including patients' demographics, psychiatric diagnoses, medications administered in the 48 hours before ECT, and information on the ECT procedure. Referring psychiatrists were advised to discontinue lithium before ECT but otherwise managed psychotropic medications as clinically indicated. A fixed charge titration schedule was used to estimate seizure threshold. Electroconvulsive therapy motor seizure duration was estimated by the cuff method, and electroencephalogram seizure duration was estimated by review of a 2-lead strip. RESULTS: Administration of psychotropic medications, including benzodiazepines, antiepileptics, selective serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, bupropion, and stimulants, was not associated with seizure threshold as estimated by electrical charge eliciting a generalized seizure or duration during the initial ECT titration. Tricyclic and tetracyclic antidepressant dosage was associated with seizure threshold. CONCLUSIONS: Psychotropic medications may have little effect on seizure threshold and duration during titration of electrical dose at ECT initiation. Integrating this work with other literature supports making recommendations for medication discontinuation before ECT on an individual basis.

Effect of electrical parameters on ECT convulsive threshold and duration.

BACKGROUND: Optimal stimulus parameters for electroconvulsive therapy (ECT) are unclear. Pulse duration and frequency related to convulsive threshold and seizure duration in the first ECT treatment in a series were evaluated. METHODS: Convulsive threshold was estimated for all patients (N = 550) receiving ECT over 27 months. Thresholds were estimated using different brief pulse stimulators, starting with a dose of approximately 25 mC per pulse train for right unilateral (RUL) stimulation (50 mC for bilateral [BL] stimulation). The charge was applied in 25-mC serial increments (approximately doubling for BL stimulation) up to approximately 100 mC (>200 mC for BL stimulation) to a generalized motor seizure endpoint. Patients lacking seizure response at 100 mC (200 mC for BL stimulation) received >500 mC. RESULTS: Convulsive threshold increased with age, African American identity, diagnosis other than depression, and female sex, and decreased with RUL electrode placement, low frequency (30 Hz), and brief pulse width (0.5 msec). RUL stimulation and lower anesthetic medication doses promoted longer seizures. Younger patients had longer seizures than older patients. Pulse width and frequency did not affect seizure duration. Lower charge yielded longer seizures. CONCLUSIONS: ECT efficiency appears to be achieved by lower frequency and briefer pulse duration stimulation. Randomized trials are needed for corroboration of these findings.

Antipsychotic patterns of use in patients with schizophrenia: polypharmacy versus monotherapy.

BACKGROUND: The objective of this study was to characterize real-world treatment patterns in the prescription of antipsychotic polypharmacy (≥ 2 concurrent antipsychotics) compared with antipsychotic monotherapy for patients with schizophrenia. METHODS: This study was a retrospective claims-based analysis of patients (aged 13-64 years) with schizophrenia belonging to an employer-based health plan. Duration of therapy was measured as the number of treatment days over one year following the initial date of antipsychotic therapy. Discontinuation was defined as a 90-day gap in antipsychotic treatment (or in at least one antipsychotic for the polypharmacy group). Logistic regression analyses were used to predict discontinuation within one year. Ordinary Least Squares (OLS) regressions were used to predict duration of therapy (by type of therapy) when controlling for gender, region, number of somatic and psychiatric comorbidities, Deyo-Charlson comorbidity score, and number of psychiatric and somatic medications. RESULTS: Of the 4,156 patients, 3,188 received monotherapy and 968 received polypharmacy. Mean age was 40 years (37.8 years for polypharmacy vs 40.3 years for monotherapy, p < 0.001). Within one year, 77% of the polypharmacy group and 54% of the monotherapy group discontinued treatment. The average duration of therapy was 163 [SD = 143] days in the polypharmacy group vs 253 [SD = 147] days in the monotherapy group. In both cohorts, patients <25 years had a higher frequency of discontinuations than those ≥ 26 years. Age and polypharmacy were independent predictors of treatment duration and discontinuation prior to one year. CONCLUSIONS: One quarter of patients with schizophrenia received antipsychotic polypharmacy. Discontinuation was higher in the polypharmacy group. Age and polypharmacy were significant predictors of treatment discontinuation.

Pharmacological strategies in the prevention of relapse after electroconvulsive therapy.

OBJECTIVE: To determine whether starting antidepressant medication at the start of electroconvulsive therapy (ECT) reduces post-ECT relapse and to determine whether continuation pharmacotherapy with nortriptyline (NT) and lithium (Li) differs in efficacy or adverse effects from continuation pharmacotherapy with venlafaxine (VEN) and Li. METHODS: During an acute ECT phase, 319 patients were randomized to treatment with moderate dosage bilateral ECT or high-dosage right unilateral ECT. They were also randomized to concurrent treatment with placebo, NT, or VEN. Of 181 patients to meet post-ECT remission criteria, 122 (67.4%) participated in a second continuation pharmacotherapy phase. Patients earlier randomized to NT or VEN continued on the antidepressant, whereas patients earlier randomized to placebo were now randomized to NT or VEN. Lithium was added for all patients who were followed until relapse or 6 months. RESULTS: Starting an antidepressant medication at the beginning of the ECT course did not affect the rate or timing of relapse relative to starting pharmacotherapy after ECT completion. The combination of NT and Li did not differ from VEN and Li in any relapse or adverse effect measure. Older age was strongly associated with lower relapse risk, whereas the type of ECT administered in the acute phase and medication resistance were not predictive. Across sites, 50% of the patients relapsed, 33.6% continued in remission 6 months after ECT, and 16.4% dropped out. CONCLUSIONS: Starting an antidepressant medication during ECT does not affect relapse, and there are concerns about administering Li during an acute ECT course. Nortriptyline and VEN were equally effective in prolonging remission, although relapse rates after ECT are substantial despite intensive pharmacology. As opposed to the usual abrupt cessation of ECT, the impact of an ECT taper should be evaluated.

Identifying inadequate response among patients with ankylosing spondylitis and psoriatic arthritis prescribed advanced therapy in a real-world, commercially insured adult population in the USA.

OBJECTIVE: This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in the USA. METHODS: Adult patients with AS or PsA who initiated advanced therapy were identified from the HealthCore Integrated Research Database®. Inadequate response to advanced therapies (tumour necrosis factor inhibitors [TNFi] and non-TNFi biologics) was identified using a claims-based algorithm. Factors influencing inadequate response were assessed using multivariable logistic regression. RESULTS: In total, 646 patients with AS, and 1433 patients with PsA were evaluated. Among patients with AS (mean age, 43 years; male, 58%), 93% patients initiated TNFi, and 69% of patients had inadequate response. In patients with PsA (mean age, 49 years; male, 47%), 67% initiated TNFi, and 77% had inadequate response. Low adherence was the main predictor of inadequate response in patients with AS (56%) and PsA (63%). Inadequate responders were more likely to be female (odds ratio [OR] 2.05 for AS and 1.37 for PsA). Prior exposure to TNFi was associated with 3.89- and 2.14-fold greater odds of inadequate response in both AS and PsA patients, respectively, while patients using methotrexate were less likely to have inadequate response (OR 0.48 for AS and 0.72 for PsA; all p < 0.05). CONCLUSIONS: Over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Health plan claims data appear useful to classify inadequate responders in AS and PsA. Key Points • Estimating inadequate response to advanced therapies and identifying factors associated with this outcome using claims data could improve treatment outcomes in AS and PsA. • In a sample of commercially insured US patients, over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Patient characteristics such as sex and prior therapy use were predictive of inadequate response to advanced therapies. • Health plan claims data appear useful to classify inadequate responders in AS and PsA and identify factors associated with this outcome.

The Relationship Between Reductions in WHO Risk Drinking Levels During Treatment and Subsequent Healthcare Costs for the ACTIVE Workgroup.

BACKGROUND: Abstinence has historically been considered the target outcome for alcohol use disorder (AUD) treatment, yet recent work has found drinking reductions after AUD treatment, as measured by World Health Organization (WHO) risk drinking levels, are associated with meaningful improvements in functioning, physical health, and quality of life. OBJECTIVES: This study extends previous analyses of AUD treatment outcomes by estimating the association between changes in WHO risk drinking levels (very high, high, medium, and low, based on average daily alcohol consumption) and healthcare costs. METHODS: Secondary data analysis of the COMBINE study, a multisite randomized clinical trial of acamprosate, naltrexone and behavioral interventions for AUD. Generalized gamma regression models were used to estimate relationships between WHOrisk drinking level reductions over the course of treatment and healthcare costs in the year after treatment (N = 964) and up to 3 years following treatment (N = 651). RESULTS: SustainedWHOrisk drinking reductions of 2 or more levels throughout treatment were associated with 52.0% lower healthcare costs ( P < 0.001) in the year following treatment, and 44.0% lower costs ( P < 0.0025) over 3 years. A reduction of exactly 1 level was associated with 34.8% lower costs over 3 years, which was not significant ( P = 0.05). Cost reductions were driven by lower inpatient behavioral health and emergency department utilization. CONCLUSIONS: Reduction in WHO risk drinking levels of at least 2 levels was associated with lower healthcare costs over 1 and 3 years. Our results add to literature showing drinking reductions are associated with improvement in health.

Health-related quality of life in a clinical trial of ECT followed by continuation pharmacotherapy: effects immediately after ECT and at 24 weeks.

OBJECTIVE: : To examine the determinants of health-related quality of life (HRQOL) immediately after a clinical trial of electroconvulsive therapy (ECT) for major depression and then again after 24 weeks of a continuation pharmacotherapy in a clinical trial comparing nortriptyline (NT) plus lithium (Li) versus venlafaxine (VEN) plus Li. METHOD: : During acute ECT, 184 patients randomized to treatment with moderate-dosage bilateral (BL) ECT or high-dosage right unilateral (RUL) ECT completed the Medical Outcomes Study Short Form-36 (SF-36) as a measure of HRQOL before and immediately after ECT. They were also randomized to concurrent treatment with placebo, NT, or VEN. Seventy-four of these met remission criteria and agreed to be further randomized to 24 more weeks of VEN + Li versus NT + Li for relapse prevention and completed a final SF-36. Cognitive testing was also completed. RESULTS: : Scores from SF-36 were low before ECT, and the SF-36 subscales reflecting mental health were particularly low. Right unilateral electrode placement was associated with better SF-36 scores immediately after ECT, even after controlling for improvement in depression. Medication assignment during ECT (VEN, NT, or placebo) was not related to immediate HRQOL outcome, and cognitive performance was not related to immediate HRQOL. Remission immediately after ECT was associated with robust improvement in SF-36 scores compared with those who did not remit. Remission status remained a strong predictor of HRQOL 24 weeks after ECT, and sustained remitters showed additional gains in HRQOL 24 weeks after ECT. Electrode placement and medication assignment were not predictors at 24 weeks. CONCLUSIONS: : Using state-of-the-art delivery of acute ECT and continuation antidepressant medication, HRQOL improves remarkably after ECT, and this improvement shows further gains with those persons who sustain remission. Health-related QOL is superior with RUL versus BL ECT in the immediate post-ECT period, but at 24-weeks HRQOL has absent or inconsistent relationship with mode of ECT delivery or type of continuation antidepressant pharmacotherapy.

Pain Medication and Corticosteroid Use in Ankylosing Spondylitis, Psoriatic Arthritis, and Rheumatoid Arthritis in the United States: A Retrospective Observational Study.

OBJECTIVE: We compared pain medication use in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) versus matched control over 2 years; a subgroup analysis assessed changes in pain medication use in patients who initiated a biologic during 12 months before and after. METHODS: This was a retrospective observational cohort study using an administrative claims database. Newly diagnosed adult patients with AS, PsA, or RA identified between 1/1/2014 and 7/31/2017 were included. Demographics, baseline characteristics, and pain medication use were described using descriptive statistics. Differences in pain medication use were assessed using McNemar's/Wilcoxon signed-rank test for categorical/continuous variables. RESULTS: The study included 2180 AS, 5681 PsA, and 34,047 RA patients to assess overall pain medication use over 2 years; 188 AS, 921 PsA, and 1599 RA patients were included to assess changes in pain medication use 12 months before and after initiation of biologic. Demographics and baseline characteristics were balanced. In the overall cohort, 74.6% AS, 75.0% PsA, and 83.0% RA patients used any pain medication at baseline versus matched control; pain medications use 2 years after diagnosis date was reported in 73.5% AS, 74.1% PsA, and 81.3% RA patients. Among AS, PsA, and RA patients, use of prescribed NSAIDs (AS: 68.1 vs. 51.1%; PsA: 51.1 vs. 42.5%; RA: 61.1 vs. 41.5%; P < 0.05), glucocorticoids (AS: 56.4 vs. 41.5%; PsA: 57.4 vs. 46.9%; RA: 88.2 vs. 75.3%; P < 0.05), and opioids (AS: 42.6 vs. 36.2% [non-significant]; PsA: 38.1 vs. 33.8%; RA: 52.0 vs. 40.4%; P < 0.05) significantly decreased 12 months after biologic initiation versus prior. CONCLUSIONS: Use of NSAIDs, glucocorticoids, and opioids are common among patients with AS, PsA, or RA, although the reported use of these co-medications after biologic initiation significantly decreases in the first year of treatment.

Detecting schizophrenia early: Prediagnosis healthcare utilization characteristics of patients with schizophrenia may aid early detection.

INTRODUCTION: Many patients exhibit subsyndromal clinical findings of schizophrenia prior to diagnosis. Early treatment may mitigate schizophrenia development, yet little is known about comorbidities and healthcare resource utilization (HCRU) in these patients before diagnosis. METHODS: This retrospective, longitudinal cohort study, conducted between January 1, 2007 and April 30, 2016, used claims data from the US HealthCore Integrated Research Database. Newly diagnosed patients with schizophrenia (International Classification of Diseases, Ninth Revision: 295.x or ICD 10 F20.%) were identified and matched (1:4) with non-schizophrenia comparators. Patients were 15-54 years of age with either ≥1 inpatient/emergency room claim with a primary schizophrenia diagnosis, or ≥2 claims in any setting with any schizophrenia diagnosis. Demographics, comorbidities, physician specialties, medications, and related services, and other HCRU were compared between cohorts for up to 5 years before diagnosis. RESULTS: The schizophrenia cohort included 6732 patients (57.4% male, mean age 30.3 years for males and 36.2 years for females). All outcomes were more prevalent in the schizophrenia cohort than the comparator cohort. Substantial comorbidity, medication use, and HCRU were observed in the schizophrenia cohort even 4-5 years before diagnosis with increasing findings approaching diagnosis. From 4-5 years to 0-12 months before diagnosis, resource use increased from 20.5% to 53.3% for atypical antipsychotics, 29.3% to 48.2% for antidepressants, and 15.1% to 35.5% for psychiatric diagnostic examinations. CONCLUSIONS: Patients with schizophrenia extensively use healthcare resources up to 5 years before diagnosis. Our findings may help with developing predictive models to identify patients at high risk of schizophrenia.

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis.

BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by inpatient hospital stays and prescription drug costs, but remained stable for comparators. Additional research is needed for the development of predictive models to aid in the identification of high-risk patients. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals. Barron is an employee of HealthCore, which received funding from Boehringer Ingelheim to conduct this study. Wallace and York were employed by HealthCore at time of this study. Isenberg is an employee of Anthem. Franchino-Elder, Sidovar, and Sand are employees of Boehringer Ingelheim.

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis.

BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by inpatient hospital stays and prescription drug costs, but remained stable for comparators. Additional research is needed for the development of predictive models to aid in the identification of high-risk patients. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals. Barron is an employee of HealthCore, which received funding from Boehringer Ingelheim to conduct this study. Wallace and York were employed by HealthCore at time of this study. Isenberg is an employee of Anthem. Franchino-Elder, Sidovar, and Sand are employees of Boehringer Ingelheim.

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

Poor health-related quality of life prior to ECT in depressed patients normalizes with sustained remission after ECT.

BACKGROUND: Health-related quality of life (HRQOL) is diminished in depressed adult outpatients and especially impaired among depressed patients referred for ECT. We compare pretreatment HRQOL in ECT and non-ECT depressed patients from two large samples, and examined whether sustained remission in depressive symptoms after ECT is associated with normalization of HRQOL. METHODS: HRQOL was measured with the Medical Outcomes Study Short Form 36 (SF36) before ECT and 6 months after ECT in an effectiveness (n=286) and an efficacy (n=243) clinical trial. RESULTS: ECT patients had very low baseline SF36 scores. With one exception, SF36 subscale scores in both trials were significantly lower than those of depressed outpatients. A minority of patients in both trials entered and sustained remission over the 24 week timeframe. Among sustained remitters, average SF36 scores were no different from normative scores of the general adult population, except that in the effectiveness study ECT patients reported less Bodily Pain (p<0.05) and better Mental Health (p<0.05), while in the efficacy study ECT patients reported more difficulty with Role-Emotional (p<0.01). LIMITATIONS: Only a modest number of patients were observed in sustained remission. CONCLUSIONS: HRQOL is very poor in patients referred for ECT. Depressed patients who experience sustained remission after ECT, however, can expect improvement in their quality of life that leaves many in a position indistinguishable from the general adult population.

Co-morbidity and utilization of medical services by pain patients receiving opioid medications: data from an insurance claims database.

We used a large medical insurance claims database to identify three groups: chronic opioid use (>180 therapeutic days, N=3726); acute opioid use (<10 therapeutic days, N=37,108); and a non-opioid group (N=337,366) who filed at least one insurance claim but none for opioids. Our results showed that although chronic opioid users represented only 0.65% of the total population, they filed 4.56% of all insurance claims, used 45% of all opioid analgesics and had much more physical and psychiatric co-morbidity than the acute opioid or non-opioid samples. Women were substantially over-represented (>63%) in the chronic pain group and used a much greater share of all medical services than males, especially as they grew older. Although our data suggest that chronic pain is optimally managed in a multidisciplinary patient- and gender-specific treatment plan, this was rarely the case with internists being the primary, and often only, physician seen. Moreover, our data suggest that opioids were often used for conditions in which they are generally not indicated (e.g. arthritis and headaches) or contraindicated by co-existing physical ailments (COPD). Finally, we conclude that adherence to the WHO analgesic ladder and other pain treatment guidelines was relatively infrequent: first, opioid extended release preparations which are ideally suited for chronic pain were used only in one in four patients; and, second, the selection of a weak (propoxyphene, codeine, and tramadol) or strong opioid (e.g. morphine and oxycodone) seemed to be driven by numerous factors not necessarily related to the intensity or duration of pain.

Effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes: short-term efficacy and adverse effects.

CONTEXT: Medication resistance is the leading indication for use of electroconvulsive therapy (ECT) in major depression. The practice of stopping antidepressant medications prior to ECT derived from studies in the 1960s and 1970s in nonresistant samples. There is also continuing controversy regarding the relative efficacy and adverse effects of right unilateral and bilateral ECT. OBJECTIVE: To test the hypotheses that, compared with placebo, concomitant treatment with nortriptline or venlafaxine during the ECT course enhances short-term efficacy without a meaningful effect on adverse effects and reduces the rate of post-ECT relapse, and to test the hypotheses that high-dose, right-sided, unilateral ECT is equivalent in efficacy to moderate-dosage bilateral ECT and retains advantages with respect to cognitive adverse effects. DESIGN: Prospective, randomized, triple-masked, placebo-controlled study conducted from 2001 through 2005. SETTING: Three university-based hospitals. PATIENTS: Of approximately 750 consecutive patients referred for ECT, 319 with a major depressive episode consented, were randomized to pharmacological or ECT treatment conditions, and received at least 1 ECT treatment. MAIN OUTCOME MEASURES: Scores on the Hamilton Rating Scale for Depression, remission rate following completion of ECT, and selective measures of cognitive adverse effects. RESULTS: Treatment with nortriptyline enhanced the efficacy and reduced the cognitive adverse effects of ECT relative to placebo. Venlafaxine resulted in a weaker degree of improvement and tended to worsen cognitive adverse effects. High-dosage right unilateral ECT did not differ or was superior to bilateral ECT in efficacy and resulted in less severe amnesia. CONCLUSIONS: The efficacy of ECT is substantially increased by the addition of an antidepressant medication, but such medications may differ in whether they reduce or increase cognitive adverse effects. High-dose, right-sided, unilateral ECT is at least equivalent to moderate-dosage bilateral ECT in efficacy, but retains advantages with respect to cognitive adverse effects.

Transcranial magnetic stimulation in the acute treatment of major depressive disorder: clinical response in an open-label extension trial.

BACKGROUND: This report describes the results of an open-label extension study of active trans-cranial magnetic stimulation (TMS) in medication-resistant patients with major depressive disorder who did not benefit from an initial course of therapy in a previously reported 6-week, randomized controlled study of active versus sham TMS. METHOD: Patients with DSM-IV-defined major depressive disorder were actively enrolled in the study from February 2004 through September 2005 and treated with left prefrontal TMS administered 5 times per week at 10 pulses per second, at 120% of motor threshold, for a total of 3000 pulses/session. The primary outcome was the baseline to endpoint change score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: In those patients who received sham in the preceding randomized controlled trial (N = 85), the mean reduction in MADRS scores after 6 weeks of open-label active TMS was -17.0 (95% CI = -14.0 to -19.9). Further, at 6 weeks, 36 (42.4%) of these patients achieved response on the MADRS, and 17 patients (20.0%) remitted (MADRS score < 10). For those patients who received and did not respond to active TMS in the preceding randomized controlled trial (N = 73), the mean reduction in MADRS scores was -12.5 (95% CI = -9.7 to -15.4), and response and remission rates were 26.0% and 11.0%, respectively, after 6 weeks of additional open-label TMS treatment. CONCLUSIONS: This open-label study provides further evidence that TMS is a safe and effective treatment of major depressive disorder. Furthermore, continued active TMS provided additional benefit to some patients who failed to respond to 4 weeks of treatment, suggesting that longer courses of treatment may confer additional therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00104611.

Pulmonary embolism after ECT.

Electroconvulsive therapy (ECT) is a safe procedure, infrequently associated with life-threatening complications. Pulmonary embolism (PE) as a complication of ECT has been rarely reported. We describe a nonfatal case of PE that developed during ECT in a 50-year-old man with depression, hypertension, and diabetes. He developed symptoms of PE immediately upon awakening from the eighth right unilateral ECT, which was later confirmed by spiral chest computed tomography. We review the literature, discussing risk factors relevant to the pathophysiology of PE and making suggestions about the management of patients with suspicious symptoms.