bluuebunny/crossref_metadata_2025_split huggingface dataset:
128 Factors Associated with Cost Savings Following Use of a Pharmacogenetic Assay in Individuals with Mood and Anxiety Disorders
Authors: Edwards Alison M , Perlis Roy H , Krause David S 
Published: April 2020

Abstract:Background:In a study conducted in the database of a large commercial healthcare insurer, we previously demonstrated that use of a commercial pharmacogenetic assay for individuals with mood disorders was associated with decreased resource utilization and cost in the 6 month period following use compared to propensity-score matched controls. We conducted a post hoc analysis to understand variables associated with high cost savings.Methods:The results and methods of the initial study have previously been described. Cases were individuals with mood and anxiety disorders who received a commercial pharmacogenetic assay (Genomind, King of Prussia PA) to inform pharmacotherapy. 817 tested individuals (cases) with mood and/or anxiety disorders were matched to 2745 controls. Overall costs were estimated to be $1,948 lower in the tested group. The differences were largely the result of lesser emergency room and inpatient utilization for cases. In the present analysis, cost difference for cases compared to their matched controls was rank ordered by decile. High cost savers were arbitrarily defined a priori as the top 20% of savers. Using multivariable modeling techniques, an ordinal logistic regression model was generated in which baseline or follow-up variables were statistically tested for independent associations with high, low, and no cost savings.Results:606 (74%) of cases were net cost savers compared to their controls (cost difference <0). High cost savers (n=121) saved on average $10,690 compared to their matched controls. They were statistically more likely to have been diagnosed with bipolar disorder (n=33/121) than low cost savers (n=57/485) or non-savers (n=31/211), and had a lower Charlson Comorbidity index. High cost savers had fewer mean number of antidepressants in the baseline period (mean=3.16) compared to non-savers (3.73) but more than low cost savers (2.72) (p<0.05 across groups). In a multivariable model, bipolar, count of antidepressants, outpatient visits, and inpatient visits were statistically associated with being a high cost saver; antidepressant count and all-cause inpatient and outpatient visits in the baseline period were inversely associated with cost savings.Conclusions:Use of a pharmacogenetic assay was associated with cost-savings in the database of a large commercial insurer. Patients with bipolar disorder were more likely to be high cost savers than individuals with other mood and anxiety disorders.Funding Acknowledgements:Genomind
129 Medication Assisted Treatment Protocol
Authors: Mathis David Michael 
Published: April 2020

Abstract:This article describes a protocol to be able to utilize medication assisted treatment options for patients dependent on opioids. The first step is using a 15-day Klonopin taper for effect detox of acute opioid withdrawal. Once detoxed, the patient can be started on low dose methadone or low dose Buprenorphine. Titration above 40 mg of Methadone, or 8 mg of buprenorphine will usually not be needed. Buprenorphine is utilized as the mono product, Subutex. Avoiding Suboxone eliminates the risk of reemergence of acute opioid withdrawal symptoms.A description of how to transition to Naltrexone is provided. There are some differences between Methadone and Buprenorphine in the transition to Naltrexone. Once the patient is transitioned to Naltrexone, the stage is set for the patient to be able to get off medication assisted treatment.
141 Moderating Perspectives of Long Acting Injectable Use of Antipsychotics: A Literature Review
Authors: Riedford Kathy 
Published: April 2020

Abstract:Long acting injectable (LAI) antipsychotics are indicated for individuals suffering from schizophrenia, delusional disorder, schizoaffective disorder and bipolar disorder. Even though LAIs have traditionally been used for a subgroup of patients who were not compliant with oral treatments or who were a high risk to others, current trends are changing with increased options and availability of these treatments. A number of factors are implicated in the reversal of this trend including perspectives of patients and perspectives of providers. There is not abundant literature available regarding robust studies to examine these perspectives, but this presentation provides a current summary of available literature.Some factors that influence perspectives of both patients and providers include knowledge about LAIs, cost of LAIs and the traditional views of these agents as being used under coercive circumstances. Altering perspectives has been a primary barrier to increase the use of these agents. Evidence clearly supports the use of early intervention for individuals with first episode psychosis, and poor medication compliance results in poorer treatment outcomes. With the potential improvement in quality of life and potentially decreasing the cost burden of this illness in society, this avenue for treatment must be a strong consideration for all involved in the treatment of the aforementioned disorders.
148 Sustainability of a Benzodiazepine Deprescribing Intervention with Primary Care Providers in a University-Based Community Clinic
Authors: Platt Lois M. , Savage Teresa A. 
Published: April 2020

Abstract:Study Objectives:In light of the opioid crisis, less attention has been focused on the long-term misuse of benzodiazepines (BZD) for anxiety and sleep disorders. The purpose of this study was to determine the sustainability of positive results (an 80% decrease in BZD prescribing) following a deprescribing intervention with primary care providers working with a low-income population at a Midwestern university-based community clinic.Method:All de-identified BZD prescriptions written by providers at the community clinic were captured using the electronic medical record. A BZD equivalency chart was used to compare the relative potencies of BZD commonly prescribed by the clinic. Each prescription was converted to a single number: the diazepam equivalent (DE). This number takes into account the potency of the drug (using diazepam as the standard), the dose of the drug, number of tablets dispensed and number of refills. The number of DE prescribed was tallied every 30 days for 6 months following the completion of a quality improvement BZD deprescribing intervention. The original intervention was implemented in 2018, with the goal of decreasing the prescription of BZD by clinic primary care providers to outpatients for insomnia or anxiety. The brief intervention combined academic detailing and pharmaceutical company detailing with a deprescribing message. Providers were given current evidence about alternatives to BZD, deprescribing schedules, and brain-storming opportunities about the management of patient concerns and resistance to change. Posters with alternatives to BZD were hung in the main provider office at the clinic. Food and “No Benzo” logo merchandise (mugs, pens) were provided to attendees of the intervention and clinic nurses. Thirty days after the intervention, the number of DE prescribed decreased by 80%.Results:Benzodiazepine prescribing (measured in DE) continued to decrease every 30 days for six months to 92-93% of pre-intervention numbers.Conclusions:Follow up of a 2018 intervention revealed sustainability of the effect of a significant decrease in benzodiazepine (BZD) prescribing in a community clinic. A brief BZD deprescribing intervention using a combination of academic detailing and pharmaceutical company detailing designed to persuade prescribers to change their behavior was effective in influencing providers to decrease the amount of BZD they prescribe. The desired result (an 80% decrease in BZD prescribing) was achieved following the original 30-day intervention. Prescription numbers continued to decrease over the next six months (to 92-93% of pre-intervention numbers), which indicates that the deprescribing intervention may have had a sustainable positive effect on provider prescribing behavior. This intervention is easy to implement and may decrease BZD prescribing, which addresses the overuse/misuse of BZD, a significant public health concern in the United States.Funding Acknowledgements: Personal funds only
158 Open-label Study of Pimavanserin Patients with Comorbid Parkinson’s Disease and Depression
Authors: Guskey Michael T. , Alva Gustavo , Aldred Jason L. , Coate Bruce , DeKarske Daryl , Cantillon Marc , Norton James C. 
Published: April 2020

Abstract:Study Objectives:Depression occurs in ~50% of Parkinson’s disease (PD) patients, increases in severity and duration as the disease progresses, and is associated with increased morbidity. Improvement of depression in PD patients is correlated with reduced physical disability and improved quality of life. We are assessing use of pimavanserin (PIM) for treatment of depression in adults with PD.Method:A Phase-2, 8-week, open-label, single-arm study is being conducted to evaluate the safety and efficacy of PIM as an adjunct to SSRI/SNRI or as monotherapy in adults with both PD and symptoms of depression (baseline Hamilton Depression Scale [17-items] total score [HAMD-17] ≥15). The primary endpoint of the study is change from Baseline to Week 8 in the HAMD-17. Secondary measures included the Clinical Global Impression (CGI) scales (improvement and severity) and Scales of Outcomes in PD-Sleep (SCOPA).Results:Interim results based on the first 34 of 40 planned patients have been evaluated: 55.9% of patients were male, and average age was 68.1 years, with 19 patients on adjunctive therapy and 15 on monotherapy. At baseline, patients had a mean (SE) HAMD-17 of 19.8(0.6). Change from Baseline to Week 8 (least squares mean [LSM] [SE]) in the HAMD-17 was –10.7(1.0) (95% CI; –12.7,–8.7; P<0.001), with significant improvement seen as early as Week 2 (–8.4[1.0]; 95% CI; –10.5,–6.4; P<0.001). Significant improvement was seen for both adjunctive treatment and monotherapy: 45.2% of patients responded to treatment (≥50% improvement on the HAMD-17) at Week 8, and 35.5% reached remission (HAMD-17 ≤7). On the Clinical Global Impressions–Improvement scale, 54.8% were much/very much improved at Week 8. Significant improvement was seen in change from Baseline to Week 8 SCOPA–Global Sleep Quality, –Nighttime Sleep, and –Daytime Sleepiness: –1.0(0.4) (95% CI; –1.7,–0.3; P=0.010), –2.1(0.7) (95% CI; –3.6,–0.6; P=0.008), –2.1(0.4) (95% CI; –3.0,–1.2; P<0.001) respectively. Twenty-one of the 34 enrolled patients have completed the study to date, and another 7 are still continuing. Thirteen patients reported adverse events, the most common being falls, UTI, diarrhea, and nausea.Conclusions:These interim data suggest that PIM as adjunctive treatment or monotherapy is associated with early improvement of depressive symptoms in patients with PD and is well tolerated. This is consistent with recently reported data of PIM in major depressive disorder. Final data will be shared at the time of this presentation. However, additional placebo-controlled data will be needed to determine fully the efficacy of PIM in patients with comorbid PD and depression.Funding Acknowledgements:ACADIA Pharmaceuticals Inc.
159 Safety and Efficacy of Lurasidone in Children and Adolescents with Bipolar Depression: Results from a 2-Year Open-label Extension Study
Authors: DelBello Melissa P. , Goldman Robert , Tocco Michael , Deng Ling , Pikalov Andrei 
Published: April 2020

Abstract:Background:Bipolar I disorder frequently has an early onset, with an estimated prevalence rate of 1.8% in pediatric populations. Early onset is associated with a high degree of chronicity; however, limited data are available on the long-term efficacy of drug therapies in pediatric populations. The aim of the current study was to evaluate the long-term safety and efficacy of lurasidone in children and adolescents with bipolar depression.Method:Patients 10-17 years with bipolar I depression were randomized to 6 weeks of double-blind (DB) treatment with lurasidone or placebo. Patients who completed the study were eligible to enroll in a 2-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20-80 mg/d; LUR-LUR) or switched from placebo to lurasidone (PBO-LUR). The primary efficacy measure was the Children’s Depression Rating Scale, Revised (CDRS-R); response was defined as ≥50% reduction from DB baseline in the CDRS-R total score.Results:A total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) completed 52 weeks, and 168 (54.9%) completed 104 weeks of treatment. Mean CDRS-R total score at DB baseline was 59.4 in patients treated with lurasidone, and 58.7 in patients treated with placebo; and mean CDRS-R total score at OL baseline (after 6 weeks of DB treatment) was 36.6 in the LUR-LUR group and 41.9 in the PBO-LUR group. For the total sample of patients in the OL study, mean change (from OL baseline) in the CDRS-R score was -13.4 at week 52 and -16.4 at week 104; and responder rates were 51.0% at OL baseline (64.5% for LUR-LUR; 36.9% for PBO-LUR), 88.4% at week 52, and 91.1% at week 104. During OL treatment with lurasidone, 31 patients (10.1%) discontinued due to an adverse event. The most commonly reported events were headache (23.9%), nausea (16.4%), and somnolence (9.8%). OL treatment with lurasidone was associated with few effects on metabolic parameters or prolactin. Mean change from DB baseline in weight was +4.25 kg at week 52 (vs. an expected weight gain of 3.76 kg based on CDC normative data), and +6.75 kg at week 104 (vs. CDC expected weight gain of 6.67 kg).Conclusion:Two years of treatment with lurasidone in children and adolescents with bipolar depression was generally well-tolerated, with relatively low rates of study discontinuation. Lurasidone treatment was associated with few effects on weight, metabolic parameters, and prolactin. Patients also continued to experience improvement in depressive symptoms during long-term treatment with lurasidone.Clinicaltrials.gov identifier: NCT01914393Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.
172 A Phase 3, Multicenter Study to Assess the Long-Term Safety, Tolerability, and Efficacy of Olanzapine/Samidorphan in Patients with Schizophrenia
Authors: Yagoda Sergey , Graham Christine , Simmons Adam , Arevalo Christina , Cheng Yansong , McDonnell David 
Published: April 2020

Abstract:Background: ALKS 3831, a combination of olanzapine and samidorphan (OLZ/SAM), is in development for the treatment of schizophrenia and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. We report the safety, tolerability, and efficacy of OLZ/SAM in patients with schizophrenia in a phase 3, 52-week, open-label extension study.Methods:Patients aged 18–70 years who completed a previous phase 3, 4-week, inpatient acute efficacy study were switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Study assessments included adverse events (AEs), weight, clinical laboratory testing, and Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S) scores.Results:281 patients were enrolled; 277 (mean age, 41.4 years) received ≥1 dose of study drug, and 183 (66.1%) completed the extension study. The most common reasons for discontinuation were withdrawal by patient (15.5%), loss to follow-up (6.9%), and AEs (5.8%). AEs were reported in 136 (49.1%) patients; most were mild in severity. The most common AEs were increased weight (13.4%), somnolence (8.3%), nasopharyngitis (4.0%), and headache (4.0%). Mean weight increase from baseline in patients completing 52 weeks of treatment was 1.86 kg, a 2.79% increase. No clinically significant changes in mean laboratory parameters were observed. Mean (SD) changes from baseline to week 52 in PANSS total score and CGI-S score were –16.2 (15.41) and –0.9 (0.92), respectively (both P<0.001).Discussion:OLZ/SAM was generally well tolerated with a safety profile that supports long-term treatment. During this 52-week extension study, there were improvements in schizophrenia symptoms.Funding Acknowledgements:This study was funded by Alkermes, Inc.
183 Antidepressant Adherence and Alternative Future Options in Pacific Islander Youth
Authors: Portman Will , Wang Dawei , Ruege Andrew 
Published: April 2020

Abstract:Objectives:To investigate the current response to psychopharmacology and transcranial magnetic stimulation (TMS) in Pacific Islander adolescents with Major Depressive Disorder (MDD).BACKGROUND:40-60% of youth with Major Depressive Disorder (MDD) have a limited response to current treatment protocols and require either (a) medications with a wider side effect profile, (b) intensive psychosocial programs that interfere with school, and/or (c) publicly spurned options (electroconvulsive therapy). Such results are tempered further when working with Pacific Islanders, as such youth and families have shown in multiple studies. The aversion to such standard treatment is concerning, as Native Hawaiian adolescents have a higher risk of suicide than other adolescents in Hawaii (12.9/100,000 youth per year). With this in mind, the investigators wondered how a novel, non-pharmacological approach to depression treatment in children, transcranial magnetic stimulation (TMS), would fair.METHODS:2 literature searches (utilizing Pubmed, Ovid, Google Scholar, and OneSearch) were conducted on 6/10/19: 1 investigating rTMS in adolescent depression, the other researching rTMS in depression in Native Hawaiian or other Pacific Islander youth.RESULTS:At this point in time, 10 studies exist testing TMS’ effects in children and adolescents with treatment refractory depression. 9 of said studies were open-label trials; 1 was a small (n=2) RCT (with both patients randomized to the active arm). Of those evaluating depression severity through Children’s Depression Rating Scale-revised (“CDRS-R”) scores, 100% of the trials (8/8) displayed a statistically significant improvement. None of the trials of the 1st series of searches nor the entirety of the 2nd series yielded information as to how TMS fairs in Native Hawaiian or other Pacific Islander youth.CONCLUSIONS:No studies exist that can verify the efficacy of TMS in youth, of Oceanic origin or otherwise, with the same degree of scrutiny as currently done in adults. Therefore, our group is engaging in a pilot study to evaluate the performance of TMS for the treatment of MDD in Native Hawaiian and other Pacific Islander adolescents aged 12-17; we are planning on then progressing on to a sham-controlled RCT in a larger sample size of the same population to test its efficacy in not just Pacific Islanders, but all youth.Funding Acknowledgements:no funding
184 Insulin Sensitivity and Glucose Metabolism of Olanzapine and Combination Olanzapine and Samidorphan: A Phase 1 Exploratory Study in Healthy Volunteers
Authors: Martin William , Graham Christine , Morrow Linda , Beysen Carine , Toledo Frederico G.S. , Bajorunas Daiva , Jiang Ying , Silverman Bernard , McDonnell David , Namchuk Mark N. , Newcomer John W. 
Published: April 2020

Abstract:Background:A combination of olanzapine and samidorphan (OLZ/SAM) is in development for schizophrenia to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The objective of this phase 1 exploratory study was to assess metabolic treatment effects of OLZ/SAM.Methods:Healthy, non-obese adults (18–40 years) were randomized 2:2:1 to once-daily OLZ/SAM, olanzapine, or placebo for 21 days. Assessments included oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, weight gain, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance.Results:Sixty subjects were randomized (OLZ/SAM, n=24; olanzapine, n=24; placebo, n=12); 19 (79.2%), 22 (91.7%), and 11 (91.7%), respectively, completed the study. In the OGTT, olanzapine led to significant hyperinsulinemia (P<0.0001) and significantly reduced insulin sensitivity (2-hour Matsuda index) at day 19 vs baseline (P=0.0012), changes not observed with OLZ/SAM. No significant between-group differences were observed for change from baseline in clamp-derived insulin sensitivity index at day 21. Least squares mean weight change from baseline was similar with OLZ/SAM (3.16 kg) and olanzapine (2.87 kg); both were significantly higher than placebo (0.57 kg; both P<0.01). Caloric intake significantly decreased from baseline to day 22 with OLZ/SAM (P=0.015) but not with olanzapine or placebo. Forty-nine subjects (81.7%) experienced ≥1 AE (OLZ/SAM, 87.5%; olanzapine, 79.2%; placebo, 75.0%).Conclusions:In this exploratory study, hyperinsulinemia and decreased insulin sensitivity were observed in the OGTT with olanzapine but not with OLZ/SAM or placebo. Clamp-derived insulin sensitivity index and weight changes were similar with OLZ/SAM and olanzapine in healthy subjects during the 3-week study.Funding Acknowledgements:This study was funded by Alkermes, Inc.
192 Eye’ve Seen Enough: Oculogyric Crisis in a 13 year old Male Treated for Comorbid ADHD and Psychosis After Stopping Lisdexamphetamine
Authors: Myers Capt Kathryn , Kallinicos Robert , Lucas Christopher 
Published: April 2020

Abstract:Title:Eye’ve Seen Enough: Oculogyric Crisis in a 13 year old Male Treated for Comorbid ADHD and Psychosis After Stopping LisdexamphetamineBackground:Oculogyric crisis is a dystonic movement disorder caused by sustained contractions of ocular muscles that may last minutes to hours. It is known to occur during hypodopaminergic states. Combined use of stimulants and antipsychotics increase the risk for developing a hypodopaminergic state in the brain leading to various dystonic reactions described as a stimulant-antipsychotic syndrome (SAS).Case:A unique example of SAS occurred in a 13 year-old male with comorbid ADHD and schizoaffective disorder hospitalized for acute psychotic decompensation who had been treated for several months with risperidone and lisdexamphetamine. On admission, the patient had received olanzapine 5mg ODT for acute agitation and lisdexamphetamine was discontinued. He started to cross-taper from risperidone to quetiapine. In this setting he developed dystonia including an oculogyric crisis that resolved with diphenhydramine.Conclusions:In this case the use of lisdexamphetamine and risperidone may have set up an environment where there was decreased endogenously made dopamine and up-regulation of postsynaptic dopamine receptors. Upon discontinuation of the lisdexamphetamine and acute use of additional atypical antipsychotics (olanzapine and quetiapine), the body experienced a hypodopaminergic state resulting in dystonic reactions that included an oculogyric crisis. This case is unique from previously reported cases by occurring with the use and discontinuation of lisdexamphetamine while most reported cases involved a derivative of methylphenidate as the stimulant. This report adds to the literature showing the importance of monitoring and being aware of potential medication interactions especially when treating for comorbid conditions. This is even more important to recognize after adding or removing either of these medications.Funding: no funding.