Physician Antipsychotic Overprescribing Letters and Cognitive, Behavioral, and Physical Health Outcomes Among People With Dementia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. Objective: To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients' health outcomes. Design, Setting, and Participants: This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. Interventions: PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. Main Outcomes and Measures: The primary outcome of this analysis was patients' total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Results: Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, -0.7 days; 95% CI, -1.3 to -0.1 days; P = .02) and community-dwelling patients (adjusted difference, -1.5 days; 95% CI, -1.8 to -1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, -0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, -0.2%; 95% CI -1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. Conclusions and Relevance: This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care. Trial Registration: ClinicalTrials.gov Identifier: NCT05172687.

A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.

BACKGROUND: Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs. OBJECTIVE: To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine. METHODS: We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified. RESULTS: We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment. CONCLUSIONS: Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.

Risk of long-term care admissions among Medicare beneficiaries treated with pimavanserin or quetiapine for Parkinson's disease psychosis in USA: a retrospective administrative claims database analysis.

Aim: Risk of long-term care (LTC) admission (LTCA) associated with atypical antipsychotic (AAP) use among patients with Parkinson's disease psychosis (PDP) is a major concern. However, no comparative studies have examined the differences in risk of LTC admissions between pimavanserin (PIM), the only FDA-approved AAP for PDP, and other off-label AAPs including quetiapine (QUE). Objective: To examine all-cause LTCA rates and risk among PDP patients treated with AAPs such as QUE or PIM. Methods: Analysis of Parts A, B and D claims (100% Medicare sample; 2013-2019) of Medicare beneficiaries with PDP that initiate ≥12-month continuous PIM or QUE monotherapy from 1 January 2014 to 31 December 2018 (i.e., index date) without any AAP use in the 12-month pre-index period was conducted. Outcome assessments among 1:1 propensity score-matched (31 variables - age, sex, race, region and 27 Elixhauser comorbidities) beneficiaries on PIM versus QUE included risk of all-cause skilled nursing facility stays (SNF-stays), LTC-stays, and overall LTCA (i.e., SNF-stays or LTC-stays). All-cause LTCA rates and LTCA risk were compared using logistic regression and cox proportional hazards models, respectively, controlling for demographics, comorbidities and co-existing-dementia or insomnia. Results: Of the matched sample (n = 842 for each group) from total sample (n = 9652), overall all-cause LTCA and SNF-stay rates were 23.2 and 20.2% for PIM versus 33.8 and 31.4% for QUE, respectively (p < 0.05, for each). Hazard ratio (95% CI) for risk of SNF-stay and overall LTCA was 0.78 (0.61, 0.98) and 0.80 (0.66, 0.97), respectively, for PIM versus QUE beneficiaries (p < 0.05, for each). Conclusion: The 20% lower risk of LTCA (i.e., greater delay) with PIM versus QUE in this analysis may suggest that PIM should be started early for the treatment of PDP.

Patients treated with pimavanserin or quetiapine for Parkinson's disease psychosis: analysis of health resource utilization patterns among Medicare beneficiaries.

BACKGROUND: Pimavanserin (PIM) is the only FDA approved atypical antipsychotic (AAP) for the treatment of Parkinson's Disease Psychosis (PDP) while other off-label AAPs like quetiapine (QUE) are also used. Real-world comparative effects of PIM and QUE on health resource utilization (HCRU) may provide insights about their relative benefits. OBJECTIVES: To examine annual HCRU among newly initiated PIM or QUE monotherapy among patients with PDP. METHODS: Retrospective analysis of 100% Medicare (Parts A, B, and D) claims of patients with PDP during 1 January 2013 to 31 December 2019 was conducted. Treatment-naive patients with first prescription for PIM or QUE from 1 January 2014 to 31 December 2018 were selected if they had ≥12-months continuous monotherapy and had no prior AAP use for ≥12-month pre-index. Post-index 12-month HCRU was compared between 1:1 propensity score matched (PSM) PIM or QUE cohorts. HCRU outcomes included: rates of all-cause and psychiatric-related inpatient hospitalizations by stay-type [i.e., long-term stays (LT-stays), short-term stays (ST-stays), skilled nursing facility stays (SNF-stays)], outpatient hospitalizations, emergency room (ER) visits, and office visits. Relative risk and 95% confidence intervals are reported [RR (95% CI)]. RESULTS: A total of 842 and 7,116 were treated with PIM and QUE, respectively. Mean age and gender distribution were similar among both groups. After PSM, those on PIM (n=842) had significantly lower RR for all-cause: inpatient hospitalizations [RR=0.78 (0.70-0.87)], ST-stays [RR=0.75 (0.66-0.84)], SNF-stays [RR=0.64 (0.54-0.76)], and ER visits [RR=0.91 (0.84-0.97)] vs. QUE (n=842). PIM patients had slightly higher RR for all-cause office visits [RR=1.03 (1.01-1.05)] vs. QUE. Psychiatric-related inpatient hospitalizations were also lower for PIM vs. QUE: [RR=0.63 (0.48-0.82)] ST-stays [RR=0.61 (0.43-0.86)], SNF-stay [RR=0.69 (0.47-1.02)], and ER visits [RR=0.53 (0.37-0.76)]. CONCLUSIONS: In this analysis of PDP patients, PIM monotherapy resulted in nearly 22% and 37% lower all-cause hospitalizations and psychiatric-related inpatient hospitalizations compared to QUE.

Systematic Review of Real-World Treatment Patterns of Oral Antipsychotics and Associated Economic Burden in Patients with Schizophrenia in the United States.

BACKGROUND: Schizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25-1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed. OBJECTIVE: We conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA. DATA SOURCES: We searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars. STUDY ELIGIBILITY: Observational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included. RESULTS: Eighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine. LIMITATIONS: This systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system. CONCLUSIONS: In the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies.

Schizophrenia is a debilitating mental disorder that affects up to 1.6% of adults in the USA. Antipsychotic medications reduce symptoms of the disease, but many patients with schizophrenia are not fully adherent or choose to discontinue treatment entirely, increasing their risk of hospitalization. In others, efforts to achieve better symptom control or to avoid intolerable side effects may result in switching antipsychotic medications or adding additional medications, leading to higher medical treatment costs. The magnitude of these cost increases is unclear. This study sought to assess medical costs associated with antipsychotic treatment adherence, switching, and adding additional antipsychotics. We reviewed 81 studies published from January 2008 through June 2018 examining treatment adherence in patients with schizophrenia. We calculated rates of adherence, switching, and adding antipsychotics, as well as associated medical costs. Overall adherence to antipsychotic treatment was less than 50%, with up to 50% of patients switching medications and up to 29% adding an additional antipsychotic medication to their current treatment. Patients who were not treatment adherent incurred annual medical costs of $10,316 compared with $5723 in patients who were adherent. The costs of immediate or delayed switching of antipsychotic medications ranged from $21,922 to $28,232, while costs of adding an additional antipsychotic ranged from $24,045 to $29,344. These data suggest that suboptimal medication adherence, along with high rates of patient discontinuation and medication switching, lead to higher treatment costs in the management of patients with schizophrenia.

Cost of Relapse Management in Patients with Schizophrenia in Italy and Spain: Comparison Between Lurasidone and Quetiapine XR.

BACKGROUND AND OBJECTIVE: Schizophrenia is a low-prevalence mental disorder with a global age-standardized prevalence of 21 million people (2016). Second-generation antipsychotics (lurasidone and quetiapine XR) are recommended as the first-line treatment for schizophrenia. It is interesting to investigate how the results of clinical studies translate into direct medical costs. The objective of this analysis was to assess the direct medical costs related to pharmaceutical treatments and the management of relapses in patients affected with schizophrenia treated with lurasidone (74 mg) vs quetiapine XR (300 mg) assuming the Italian and Spanish National Health Service perspective. METHODS: A health economic model was developed based on a previously published model. The analysis considered direct medical costs related to the pharmacological therapies and inpatient or outpatient management of relapses (direct medical costs referred to 2019). The probability of relapses and related costs were derived from two systematic reviews. A deterministic sensitivity analysis was implemented to test the robustness of the results. RESULTS: The use of lurasidone (74 mg) compared with quetiapine XR (300 mg) would lead to a reduction in direct medical costs in Italy and Spain, with a lower cost per patient of - 163.7 € (- 9.0%) and - 327.2 € (- 22.7%), respectively. In detail, it would lead to an increase in the cost of therapy of + 53.8% and of + 30.5% in Italy and Spain, respectively, to a decrease in the cost of relapses with hospitalization of - 135.7%, and to an increase in the cost of relapses without hospitalization of + 24.5%. CONCLUSIONS: The use of lurasidone (74 mg) for the treatment of patients affected with schizophrenia, compared with quetiapine XR (300 mg), would be a cost-saving strategy in the two contexts investigated assuming the National Health Service point of view.

Health Care Cost in Patients With Schizophrenia Treated With Brexpiprazole Versus Other Oral Atypical Antipsychotic Therapy.

PURPOSE: Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting. METHODS: This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up. FINDINGS: The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users. IMPLICATIONS: Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.

Potentially inappropriate prescriptions of anticholinergics drugs in Alzheimer's disease patients.

AIM: Alzheimer's disease is a common cause of dementia, and is usually treated with medications that elevate acetylcholine levels. The objective of the present study was to identify drugs with anticholinergic properties prescribed to patients diagnosed with Alzheimer's disease in Colombia. METHODS: A cross-sectional study was carried out in outpatients diagnosed with Alzheimer's disease who were identified from a population database from Colombia, and had been treated with cholinesterase inhibitors and glutamate N-methyl-D-aspartate receptor antagonists. The anticholinergic burden was evaluated using the Anticholinergic Cognitive Burden scale, and patients were classified on a scale of 0-3 points according to anticholinergic potential, and were grouped into those with mild-to-moderate (1-2 points) or high (≥3 points) anticholinergic load. RESULTS: The study included 4134 Alzheimer's disease patients. The mean age was 81.50 ± 8.16 years, and 67.8% were women. At least 22.9% of patients took anticholinergic drugs. Of these, the most frequently prescribed medication was quetiapine (8.6%). Age >85 years was associated with a high risk of having an anticholinergic burden ≥3 points (OR 2.19, 95%CI 1.159-4.162). Potential interactions between cholinesterase inhibitors and anticholinergic drugs were identified in 7.8% of patients. CONCLUSIONS: The majority of patients who were prescribed anticholinergic drugs were older women, had a significant total anticholinergic burden and had frequent pharmacological interactions with cholinesterase inhibitors. The use of anticholinergics reduces the clinical effectiveness of antidementia drugs and increases the risk of adverse reactions. Geriatr Gerontol Int 2019; 19: 913-917.

Medication Adherence, Health Care Utilization, and Costs in Patients With Major Depressive Disorder Initiating Adjunctive Atypical Antipsychotic Treatment.

PURPOSE: The purpose of this study was to compare medication adherence, health care utilization, and cost among patients receiving adjunctive treatment for major depressive disorder (MDD) with brexpiprazole, quetiapine, or lurasidone. METHODS: Using Truven Health MarketScan® Commercial, Medicaid, and Medicare Supplemental Databases, we identified adults with MDD initiating adjunctive treatment with brexpiprazole, quetiapine, or lurasidone (index atypical antipsychotic [AAP]). We compared medication adherence and persistence measured by proportion of days covered (PDC) and treatment duration of index AAP, all-cause and psychiatric hospital care (hospitalization or emergency department visit), and medical costs during 6-month follow-up. Models performed included logistic regression for hospital care, linear regression for PDC and cost, and Cox proportional hazards regression for time to discontinuation, adjusting for demographic, clinical, and utilization differences during the 6 months before index AAP. FINDINGS: The total sample included 778 brexpiprazole, 626 lurasidone, and 3458 quetiapine therapy initiators. Adjusting for baseline differences, the risk of discontinuation of index AAP was statistically significantly higher for quetiapine than for brexpiprazole (hazard ratio [HR] = 1.13; 95% CI, 1.02-1.25; P = 0.023) and did not differ between lurasidone and brexipiprazole (HR = 1.14; 95% CI, 1.00-1.29; P = 0.054). The adjusted rate of all-cause hospitalization or emergency department visit in the postindex period was lowest for brexpiprazole at 27.4% (95% CI, 24.0%-31.0%), compared with 31.1% (95% CI, 27.3%-35.2%) for lurasidone and 35.3% (95% CI, 33.5%-37.1%) for quetiapine (P< 0.001 for all comparisons). Quetiapine users had increased all-cause costs compared with brexpiprazole users (estimate = $2309; 95% CI, $31-$4587; P = 0.047); all-cause medical costs did not differ between lurasidone and brexpiprazole (estimate = $913; 95% CI, $-2033 -$3859; P = 0.543). Adjusted psychiatric hospital care, psychiatric costs, and PDC did not differ significantly among the groups. IMPLICATIONS: In patients with MDD and a variety of insurance types, brexpiprazole use was associated with statistically significantly lower risks of discontinuation, risk of hospital care (hospitalization and ED visits), and all-cause medical costs compared with adjunctive quetiapine. Differences between brexpiprazole and lurasidone were not statistically significant. These findings suggest that drug choice is associated with subsequent health care utilization and costs.

Effect of Peer Comparison Letters for High-Volume Primary Care Prescribers of Quetiapine in Older and Disabled Adults: A Randomized Clinical Trial.

Importance: Antipsychotic agents, such as quetiapine fumarate, are frequently overprescribed for indications not supported by clinical evidence, potentially causing harm. Objective: To investigate if peer comparison letters targeting high-volume primary care prescribers of quetiapine meaningfully reduce their prescribing. Design, Setting, and Participants: Randomized clinical trial (intent to treat) conducted from 2015 to 2017 of prescribers and their patients nationwide in the Medicare program. The trial targeted the 5055 highest-volume primary care prescribers of quetiapine in 2013 and 2014 (approximately 5% of all primary care prescribers of quetiapine). Interventions: Prescribers were randomized (1:1 ratio) to receive a placebo letter or 3 peer comparison letters stating that their quetiapine prescribing was high relative to their peers and was under review by Medicare. Main Outcomes and Measures: The primary outcome was the total quetiapine days supplied by prescribers from the intervention start to 9 months. Secondary outcomes included quetiapine receipt from all prescribers by baseline patients, quetiapine receipt by patients with low-value or guideline-concordant indications for therapy, mortality, and hospital use. In exploratory analyses, the study followed outcomes to 2 years. Results: Of the 5055 prescribers, 231 (4.6%) were general practitioners, 2428 (48.0%) were in family medicine, and 2396 (47.4%) were in internal medicine; 4155 (82.2%) were male. All were included in the analyses. Over 9 months, the treatment arm supplied 11.1% fewer quetiapine days per prescriber vs the control arm (2456 vs 2864 days; percentage difference, 11.1% fewer days; 95% CI, -13.1% to -9.2% days; P < .001; adjusted difference, -319 days; 95% CI, -374 to -263 days; P < .001), which persisted through 2 years (15.6% fewer days; 95% CI, -18.1% to -13.0%; P < .001). At the patient level, individuals in the treatment arm received 3.9% (95% CI, -5.0% to -2.9%; P < .001) fewer days of quetiapine from all prescribers over 9 months, with a larger decrease among patients with low-value vs guideline-concordant indications (-5.9% [95% CI, -8.0% to -3.9%] vs -2.4% [95% CI, -4.0% to -0.9%], P = .01 for test that effects were equal for both patient groups). There was no evidence of substitution to other antipsychotics, and 9-month mortality and hospital use were similar between the treatment vs control arms. Conclusions and Relevance: Peer comparison letters caused substantial and durable reductions in quetiapine prescribing, with no evidence of negative effects on patients. Trial Registration: ClinicalTrials.gov identifier: NCT02467933.

Changes in healthcare resource use and costs associated with early versus delayed initiation of atypical antipsychotic adjunctive treatment in major depressive disorder.

AIMS: The study compared all-cause and major depressive disorder (MDD)-related healthcare resource use (HRU) and costs in patients with MDD treated with atypical antipsychotic (AAP) adjunctive therapy early or later in treatment. MATERIALS AND METHODS: Adults with MDD and antidepressant treatment (ADT) who newly initiated adjunctive aripiprazole, brexpiprazole, lurasidone, or quetiapine between October 1, 2014 and September 30, 2015 were identified in the IQVIA Real-World Data Adjudicated Claims database; the index date was the date of the first AAP claim. Patients were stratified into three cohorts: AAP initiated in the first year (Y1); in the second year (Y2); and more than 2 years (Y3) of first ADT use. Within each cohort, HRU and costs were compared between the 12 months before and after the index date. Pre-post changes in HRU and costs were then compared between cohorts. RESULTS: Five hundred and six (36.7%) patients were categorized as Y1; 252 (18.3%) as Y2; and 622 (45.1%) as Y3. AAP use was associated with significantly decreased rates of all-cause and MDD-related hospitalization and emergency department visits, and increased rates of pharmacy fills and physician office visits; and the magnitude of changes was largest in cohort Y1. Cohort Y1 had the largest reductions in mean (±SD) all-cause medical costs per patient (-$10,496 ± $85,022, p = .015) compared to Y2 (-$2,474 ± $85,022, p = .572) and Y3 (-$472 ± $31,334, p = .823), mainly due to the reduction in hospitalization. After adjusting for differences in baseline characteristics, the largest reductions in hospitalization and medical costs were observed in cohort Y1. Similar increases in all-cause pharmacy costs were seen in all cohorts. A similar trend in costs was observed in MDD-related healthcare services. LIMITATIONS AND CONCLUSIONS: AAP treatment was associated with reductions in all-cause and MDD-related medical costs, primarily in decreased hospitalization. The reductions were largest among patients who initiated treatment in the first year.

Hospitalization outcomes in patients with schizophrenia after switching to lurasidone or quetiapine: a US claims database analysis.

BACKGROUND: This study compared hospital admission rates among adult patients with schizophrenia who switched to antipsychotic monotherapy with lurasidone or quetiapine. METHODS: This retrospective cohort study used U.S.-based Truven Health MarketScan® Medicaid Multi-State Database (April 2010 through December 2012) and MarketScan® Commercial Claims and Encounters Database (April 2010 through October 2013). Continuous enrollment for 6-months before and after medication initiation was required. Treatment episodes ended after 6-months post lurasidone or quetiapine initiation, a 60-day treatment gap, or initiation of another antipsychotic. Length of treatment episodes (i.e., treatment duration) was compared using a t-test. All-cause, mental-health, and schizophrenia-related hospitalization rates, as well as costs, were compared between lurasidone- and quetiapine-treated patients using multivariable generalized linear models that adjusted for background characteristics. RESULTS: Quetiapine (n = 435) compared to lurasidone (n = 238) treatment was associated with increased all-cause (21% vs 13%, p < 0.05) and mental health-related hospitalizations (20% vs 12%, p < 0.05), but similar rates of schizophrenia-related hospitalizations (14% vs. 10%, p = 0.14). After adjusting for baseline covariates, quetiapine had 64% higher likelihood of all-cause hospitalizations (OR [odds ratio] = 1.64, 95% confidence interval [CI] 1.05-2.57, p = 0.03), 74% higher likelihood of mental health-related hospitalizations (OR = 1.74, 95% CI 1.11-2.75, p = 0.02), and a similar likelihood of schizophrenia-related hospitalization (OR = 1.35, 95% CI 0.82-2.22, p = 0.24). For those with hospital admissions, adjusted all-cause admission costs were higher for quetiapine when compared with lurasidone in both the Medicaid ($22,036 vs. $15,424, p = 0.17) and commercial populations ($23,490 vs. $20,049, p = 0.61). These differences were not significant. The length of treatment episodes was significantly shorter for quetiapine than lurasidone (115.4 vs 123.1 days, p < 0.05). CONCLUSIONS: In this retrospective claims database study, patients with schizophrenia who were switched to lurasidone had significantly fewer all-cause and mental health-related hospitalizations and similar rates of schizophrenia-related hospitalization compared with those switched to quetiapine. Patients switching to lurasidone had a significantly longer treatment duration rate than those switching to quetiapine. These results may reflect differences in efficacy or tolerability between lurasidone and quetiapine.

Antipsychotic Prescribing and Safety Monitoring Practices in Children and Youth: A Population-Based Study in Alberta, Canada.

BACKGROUND AND OBJECTIVE: Antipsychotic medication use has steadily increased in Canada, with an expansion in the profile of users and the diagnoses for which they are used. The use of antipsychotics is associated with a number of adverse effects for which routine monitoring is recommended. The objectives of this study were to determine the most common diagnoses associated with antipsychotic use in children in Alberta, Canada and the proportion who receive recommended laboratory tests for adverse effects. METHODS: Data on dispensed antipsychotics, diagnoses, prescribers, and laboratory testing were obtained from provincial data sources. To assess the frequency of metabolic and hormonal laboratory baseline and/or follow-up testing, the sample was divided into an antipsychotic-naïve cohort and an antipsychotic non-naïve cohort. RESULTS: In 2014, 6916 children were dispensed at least one second- or third-generation antipsychotic. The most frequently dispensed antipsychotics were risperidone (3908 children), quetiapine (2140 children), and aripiprazole (1302 children). The majority of children prescribed risperidone were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) or conduct disorder. Quetiapine was mainly prescribed for neurotic disorder or depression, while aripiprazole was prescribed most frequently for conduct disorder or neurotic disorders. Among antipsychotic-naïve patients, 17% had at least one laboratory test done at baseline, and 35% had at least one laboratory test done at follow-up. In the non-naïve patients, 42% had at least one follow-up laboratory test. Lipid and glucose testing were done in less than 5% of the naïve cohort at baseline, and in less than 15% at follow-up. In the non-naïve cohort, less than 22% received lipid or glucose testing during the year 2014. CONCLUSIONS: The majority of antipsychotic use in children in Alberta is off-label and associated with disruptive behavior disorders, depression, and anxiety disorders. The vast majority of children prescribed antipsychotic medications do not undergo recommended laboratory tests.

Results from a drug utilization study of extended release quetiapine fumarate prescribed by psychiatrists as treatment for major depressive disorder in selected countries in the European Union.

This multicenter, observational drug utilization (DU) study (NCT01594996) investigated the profile of patients and specialist providers who prescribed extended release quetiapine fumarate (quetiapine XR) for treatment of major depressive disorder (MDD) across five European countries (Germany, Italy, Romania, Spain, and Sweden). A DU data abstraction form captured information on the characteristics of physicians, patients, and drugs utilized in the medical management of depressive episodes in MDD, where the therapeutic regimen included quetiapine XR. Data were reported descriptively. This analysis included 811 patients. Psychiatric histories indicated a burden of severe MDD in these patients. Patient demographics were similar across countries; however, those in Sweden had a younger mean age. Physicians' ratings of the therapeutic effect of prior treatment with antidepressants suggested the need for an add-on treatment for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment as monotherapy. Presence of psychotic symptoms during depressive episodes predicted treatment with higher than recommended doses of quetiapine XR (odds ratio=3.11; 95% confidence interval: 1.6-6.0). This analysis demonstrated similarities in DU across the countries analyzed, largely in accordance with the recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in MDD (50-300 mg/day).

Real-world adherence assessment of lurasidone and other oral atypical antipsychotics among patients with schizophrenia: an administrative claims analysis.

OBJECTIVE: To compare adherence with lurasidone to other oral atypical antipsychotics among Medicaid and commercially insured patients with schizophrenia. RESEARCH DESIGN AND METHODS: Administrative claims of patients with schizophrenia treated with atypical antipsychotics (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) from October 2010 to September 2011 were identified from MarketScan Commercial and Medicaid Databases, and were classified by the first (index) antipsychotic. Patients were 18-64 years, had insurance coverage 12 months pre- and 6 months post-index, and no pre-index use of the index drug. MAIN OUTCOME MEASURES: Medication possession ratio (MPR), discontinuation rate, and mean time to discontinuation were assessed post-index. Pairwise comparisons (lurasidone versus each drug) were conducted using chi-square tests and Student's t-tests. RESULTS: There were 146 Medicaid (mean age 43.5 years, 47.9% female) and 63 commercial (mean age 40.0 years, 42.9% female) patients treated with lurasidone. In the Medicaid population, the MPR for patients treated with lurasidone was 0.60, versus 0.41-0.48 for patients treated with other antipsychotics (all p < .05). Patients treated with lurasidone exhibited a lower discontinuation rate compared to patients treated with all other antipsychotics (49.3% versus 62.3%-68.3%, all p < .05). The mean time to discontinuation with lurasidone was significantly longer than with ziprasidone (p < .05). In the commercial population, the MPR for patients treated with lurasidone (0.61) was higher compared to patients treated with quetiapine (0.44) and ziprasidone (0.43) (both p < .05). The discontinuation rate (44.4%) was lower for patients treated with lurasidone compared to patients treated with all other antipsychotics except risperidone (p < .05). The mean time to discontinuation was longer for lurasidone than with other antipsychotics. CONCLUSIONS: In Medicaid and commercial populations, patients treated with lurasidone demonstrated greater adherence compared to patients treated with other atypical antipsychotics. Limitations of using administrative claims data include potential errors or inconsistencies in coding, and lack of complete clinical information.

Cost-effectiveness of brexpiprazole adjunctive treatment for major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a debilitating psychiatric illness with a high cost burden. This analysis evaluates the cost-effectiveness of adjunctive brexpiprazole versus comparator branded adjunctive treatment for MDD and background antidepressant therapy (ADT) alone from a US payer perspective. METHODS: An economic model was developed to assess the cost-effectiveness of brexpiprazole versus comparator adjunctive treatment and ADT alone on total direct medical costs using a 6-week cycle time frame for a total of 48 weeks, with treatment response and remission as primary outcomes. The model consisted of 3 parts, 1 to represent the acute treatment phase and 2 to represent the maintenance stage. RESULTS: In the base-case analysis, brexpiprazole as reference treatment resulted in cost per additional responder ranging from $19,442-$48,745 and cost per additional remitter ranging from $27,196-$71,839 versus comparator treatments over 48 weeks. Sensitivity analyses showed treatment with brexpiprazole was more costly, but more clinically effective in all probabilistic simulations. LIMITATIONS: This representation of disease natural history over 48 weeks may not account for all possible health states. Resource utilization on treatment was estimated using the resource use data from previous trials, and may overestimate medical costs compared to the real-world setting. Treatment comparators were limited to branded therapies, and head-to-head studies were not available to obtain data inputs. CONCLUSION: Compared to other branded adjunctive therapies, brexpiprazole increases response and remission at 6 weeks; medical care cost savings were observed with the use of brexpiprazole. These findings may assist clinicians and formulary decision makers when selecting treatment for MDD.

Prescription preferences in antipsychotics and attitude towards the pharmaceutical industry in Belgium.

OBJECTIVES: The number of antipsychotic prescriptions are increasing rapidly worldwide, a trend which is mainly driven by the steep rise in second-generation antipsychotic (SGA) prescriptions. However, the success of SGA, compared with the older first-generation antipsychotics (FGAs), cannot be explained by evidence. Several studies concluded on equal efficacy of FGA and SGA on positive, negative and cognitive symptoms of schizophrenia. Next to that, the influence of the pharmaceutical industry on prescription behaviour has drawn considerable interest. Therefore, the relationship between antipsychotic prescription patterns and exposure to information directly provided by pharmaceutical companies was studied. METHODS: A cross-sectional online survey, addressing psychiatrists, general practitioners (GPs) and trainees in Flanders, was carried out. Respondents were questioned about their prescription behaviour, opinion about efficacy of SGA versus FGA and the nature and frequency of their contact with the pharmaceutical industry. Using Spearman's rank correlations and χ2 tests, the relationship between different variables and group differences were examined. RESULTS: Psychiatrists, GPs and trainees in Flanders clearly favour olanzapine and risperidone, followed by quetiapine and aripiprazole above all other agents. This behaviour is supported by the conviction that SGAs have superior efficacy and a more benign side effect profile, compared with FGA. Frequent contact with drug representatives is correlated with a preference of SGA over FGA. 41% of the respondents acknowledge to be influenced by the pharmaceutical industry, which is more than that previously reported.

Fluphenazine (oral) versus atypical antipsychotics for schizophrenia.

BACKGROUND: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years. OBJECTIVES: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia. SEARCH METHODS: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics. DATA COLLECTION AND ANALYSIS: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence. MAIN RESULTS: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness. AUTHORS' CONCLUSIONS: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

Quetiapine use in adults in the community: a population-based study in Alberta, Canada.

OBJECTIVE: The objective of this study was to evaluate trends in prescribing of the second-generation antipsychotic medication quetiapine to adults in the province of Alberta from 2008 to 2013 through examination of dispensed prescriptions, and diagnoses associated with users of quetiapine in 2013. METHODS: We analysed administrative data from Alberta Health; the Alberta Pharmaceutical Information Network (PIN) Dispenses health data set, the Practitioner Payments (Fee-For-Service claims) health data set and the Population Registry health data set. These data sets allowed us to identify discrete quetiapine recipients for each calendar year from 2008 to 2013. To evaluate diagnoses associated with users of quetiapine, we evaluated diagnostic codes used by physicians in billings claims in 2013. RESULTS: Quetiapine use increased over the 6-year time period studied. In 2008, there were 16,087 unique quetiapine recipients in Alberta (7.2 per 1000). By 2013, there were 35,314 unique quetiapine recipients (13.3 per 1000). Use by women was higher than men at all time points. Depression was most common diagnosis associated with quetiapine recipients, which was present in 56% of users of quetiapine. Other common diagnoses associated with quetiapine use included neurotic disorders, bipolar disorder and sleep disturbances. CONCLUSIONS: The current study of quetiapine use in the province of Alberta provides confirmatory data of the increasing use of quetiapine for the treatment of depression and anxiety disorders. Safe and rational prescribing practices must be encouraged in light of the modest advantages of quetiapine over no treatment as an adjunctive treatment of major depression, and the known harms of this medication.

Assessment and treatment of insomnia in adult patients with alcohol use disorders.

Insomnia in patients with alcohol dependence has increasingly become a target of treatment due to its prevalence, persistence, and associations with relapse and suicidal thoughts, as well as randomized controlled studies demonstrating efficacy with behavior therapies and non-addictive medications. This article focuses on assessing and treating insomnia that persists despite 4 or more weeks of sobriety in alcohol-dependent adults. Selecting among the various options for treatment follows a comprehensive assessment of insomnia and its multifactorial causes. In addition to chronic, heavy alcohol consumption and its effects on sleep regulatory systems, contributing factors include premorbid insomnia; co-occurring medical, psychiatric, and other sleep disorders; use of other substances and medications; stress; environmental factors; and inadequate sleep hygiene. The assessment makes use of history, rating scales, and sleep diaries as well as physical, mental status, and laboratory examinations to rule out these factors. Polysomnography is indicated when another sleep disorder is suspected, such as sleep apnea or periodic limb movement disorder, or when insomnia is resistant to treatment. Sobriety remains a necessary, first-line treatment for insomnia, and most patients will have some improvement. If insomnia-specific treatment is needed, then brief behavioral therapies are the treatment of choice, because they have shown long-lasting benefit without worsening of drinking outcomes. Medications work faster, but they generally work only as long as they are taken. Melatonin agonists; sedating antidepressants, anticonvulsants, and antipsychotics; and benzodiazepine receptor agonists each have their benefits and risks, which must be weighed and monitored to optimize outcomes. Some relapse prevention medications may also have sleep-promoting activity. Although it is assumed that treatment for insomnia will help prevent relapse, this has not been firmly established. Therefore, insomnia and alcohol dependence might be best thought of as co-occurring disorders, each of which requires its own treatment.