Health care resource utilization and costs associated with psychiatric comorbidities in adult patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition with extensive psychiatric comorbidities. ADHD has been associated with substantial clinical and economic burden; however, little is known about the incremental burden specifically attributable to psychiatric comorbidities of ADHD in adults. OBJECTIVE: To assess the impact of psychiatric comorbidities, specifically anxiety and depression, on health care resource utilization (HRU) and costs in treated adults with ADHD in the United States. METHODS: A retrospective case-cohort study was conducted. Adults with ADHD were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was defined as the date of initiation of a randomly selected ADHD treatment. The baseline period was defined as the 6 months prior to the index date, and the study period as the 12 months following the index date. Patients with at least 1 diagnosis for anxiety and/or depression during both the baseline and study periods were classified in the ADHD+anxiety/depression cohort, whereas those without diagnoses for anxiety or depression at any time were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts with similar baseline characteristics. All-cause HRU and health care costs were assessed during the study period and compared between cohorts using regression analyses. Cost analyses were also conducted in subgroups stratified by comorbid conditions. RESULTS: After reweighting, patients in the ADHD-only cohort (N = 276,906) and ADHD+anxiety/depression cohort (N = 217,944) had similar characteristics (mean age 34.1 years; 54.8% male). All-cause HRU was higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 4.5, emergency department visits: 1.8, outpatient visits: 2.0, and psychotherapy visits: 6.4; all P < 0.01). All-cause health care costs were more than 2 times higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (mean per-patient per-year [PPPY] costs in ADHD-only vs ADHD+anxiety/depression cohort: $5,335 vs $11,315; P < 0.01). Among the ADHD+anxiety/depression cohort, average all-cause health care costs were $9,233, $10,651, and $15,610 PPPY among subgroup of patients with ADHD and only anxiety, only depression, and both anxiety and depression, respectively. CONCLUSIONS: Comorbid anxiety and depression is associated with additional HRU and costs burden in patients with ADHD. Comanagement of these conditions is important and has the potential to alleviate the burden experienced by patients and the health care system.

Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release.

BACKGROUND: Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are lacking. OBJECTIVE: To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC). METHODS: This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials. RESULTS: After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all P < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; P < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all P < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all P < 0.05) and no statistically significant difference in the change in AISRS score. CONCLUSIONS: In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison. STUDY REGISTRATION NUMBERS: NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.

Costs associated with adverse events during treatment episodes for adult attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) medication is frequently associated with adverse events (AEs), but limited real-world data exist regarding their costs from a payer's perspective. Therefore, this study evaluated the healthcare costs associated with common AEs among adult patients treated for ADHD in the US. METHODS: Eligible adults treated for ADHD were identified from a large US claims database (1 October 2015-30 September 2021). A retrospective cohort study design was used to assess excess healthcare costs and costs directly related to AE-specific claims per-patient-per-month (PPPM) associated with 10 selected AEs during ADHD treatment. To account for all costs associated with the AE, treatment episodes with a given AE were compared to similar treatment episodes without this AE. Entropy balancing was used to create cohorts with similar characteristics. Studied AEs were selected based on their prevalence in clinical trials for common ADHD medications and were identified from ICD-10-CM diagnosis codes recorded in claims. RESULTS: Among the 461,464 patients included (mean age: 34.2 years; 45.5% males), 49.4% had ≥1 AE during their treatment episode. Treatment episodes with AEs were associated with statistically significant AE-specific medical costs (erectile dysfunction: $57; fatigue: $82; dry mouth: $90; diarrhea: $162; insomnia: $147; anxiety: $281; nausea: $299; constipation: $356; urinary hesitation: $491; feeling jittery: $723) and excess healthcare costs PPPM (erectile dysfunction: $120, fatigue: $248, insomnia: $265, anxiety: $380, diarrhea: $441, dry mouth: $485, nausea: $709, constipation: $802, urinary hesitation: $1,105, feeling jittery: $1,160; p < .05). LIMITATIONS: AEs were identified based on recorded diagnosis on medical claims and likely represent more severe AEs. Therefore, costs may not be representative of milder AEs. CONCLUSIONS: This study found that AEs occurring during ADHD treatment episodes are associated with significant healthcare costs. This highlights the potential of treatments with favorable safety profiles to alleviate the burden experienced by patients and the healthcare system.

A real-world assessment of healthcare costs associated with agitation in Alzheimer's dementia.

AIMS: To describe and compare clinical characteristics, healthcare costs, and institutionalization/mortality outcomes among patients with and without agitation associated with Alzheimer's dementia (AAD). METHODS: Data from the Reliant Medical Group database (01/01/2016-03/31/2020) were used, including claims, electronic medical records, and clinical information/physician notes abstracted from medical charts. Patients aged ≥55 years with Alzheimer's dementia (AD) were observed during a randomly selected 12-month study period after AD diagnosis. Using information recorded in medical charts, patients were classified into cohorts based on experiencing (agitation cohort) and not experiencing (no agitation cohort) agitated behaviours during the study period. Entropy balancing was used to create reweighted cohorts with similar characteristics. Study outcomes (patient demographic and clinical characteristics, treatments received, healthcare costs, institutionalization and death events) were compared between cohorts; agitation characteristics were described for the agitation cohort only. RESULTS: Among 711 patients included in the study, 240 were classified in the agitation cohort and 471 in the no agitation cohort. After reweighting, several comorbidities were more frequently observed in the agitation versus no agitation cohort, including infection, depression, and altered mental status. Use of antidepressants, anticonvulsants, antipsychotics, and antianxiety medications was more common in the agitation versus no agitation cohort. Common agitated behaviours included hitting (20.8%), pacing/aimless wandering (17.5%), and cursing/verbal aggression (15.0%). Total all-cause healthcare costs were $4287 per-patient-per-year higher in the agitation cohort versus no agitation cohort (p = 0.04), driven by higher inpatient costs. Death was more common and time to death and institutionalization were shorter in the agitation versus no agitation cohort. LIMITATIONS: Results may not be generalizable to the US population with AD. CONCLUSIONS: Among patients with AD, agitation was associated with shorter time to death/institutionalization and increased comorbidities, medication use, and healthcare costs, highlighting the additional clinical and economic burden that agitation poses to patients and the healthcare system.

Risk factors associated with newly diagnosed attention-deficit/hyperactivity disorder in adults: a retrospective case-control study.

BACKGROUND: Knowledge of risk factors for attention-deficit/hyperactivity disorder (ADHD) may facilitate early diagnosis; however, studies examining a broad range of potential risk factors for ADHD in adults are limited. This study aimed to identify risk factors associated with newly diagnosed ADHD among adults in the United States (US). METHODS: Eligible adults from the IQVIA PharMetrics® Plus database (10/01/2015-09/30/2021) were classified into the ADHD cohort if they had ≥ 2 ADHD diagnoses (index date: first ADHD diagnosis) and into the non-ADHD cohort if they had no observed ADHD diagnosis (index date: random date) with a 1:3 case-to-control ratio. Risk factors for newly diagnosed ADHD were assessed during the 12-month baseline period; logistic regression with stepwise variable selection was used to assess statistically significant association. The combined impact of selected risk factors was explored using common patient profiles. RESULTS: A total of 337,034 patients were included in the ADHD cohort (mean age 35.2 years; 54.5% female) and 1,011,102 in the non-ADHD cohort (mean age 44.0 years; 52.4% female). During the baseline period, the most frequent mental health comorbidities in the ADHD and non-ADHD cohorts were anxiety disorders (34.4% and 11.1%) and depressive disorders (27.9% and 7.8%). Accordingly, a higher proportion of patients in the ADHD cohort received antianxiety agents (20.6% and 8.3%) and antidepressants (40.9% and 15.8%). Key risk factors associated with a significantly increased probability of ADHD included the number of mental health comorbidities (odds ratio [OR] for 1 comorbidity: 1.41; ≥2 comorbidities: 1.45), along with certain mental health comorbidities (e.g., feeding and eating disorders [OR: 1.88], bipolar disorders [OR: 1.50], depressive disorders [OR: 1.37], trauma- and stressor-related disorders [OR: 1.27], anxiety disorders [OR: 1.24]), use of antidepressants (OR: 1.87) and antianxiety agents (OR: 1.40), and having ≥ 1 psychotherapy visit (OR: 1.70), ≥ 1 specialist visit (OR: 1.30), and ≥ 10 outpatient visits (OR: 1.51) (all p < 0.05). The predicted risk of ADHD for patients with treated anxiety and depressive disorders was 81.9%. CONCLUSIONS: Mental health comorbidities and related treatments are significantly associated with newly diagnosed ADHD in US adults. Screening for patients with risk factors for ADHD may allow early diagnosis and appropriate management.

Treatment Patterns Among Patients with Attention-Deficit/Hyperactivity Disorder and Comorbid Anxiety and/or Depression in the United States: A Retrospective Claims Analysis.

INTRODUCTION: Patients with attention-deficit/hyperactivity disorder (ADHD) often have psychiatric comorbidities that may confound diagnosis and affect treatment outcomes and costs. The current study described treatment patterns and healthcare costs among patients with ADHD and comorbid anxiety and/or depression in the United States (USA). METHODS: Patients with ADHD initiating pharmacological treatments were identified from IBM MarketScan Data (2014-2018). The index date was the first observed ADHD treatment. Comorbidity profiles (anxiety and/or depression) were assessed during the 6-month baseline period. Treatment changes (discontinuation, switch, add-on, drop) were examined during the 12-month study period. Adjusted odds ratios (ORs) of experiencing a treatment change were estimated. Adjusted annual healthcare costs were compared between patients with and without treatment changes. RESULTS: Among 172,010 patients with ADHD (children [aged 6-12] N = 49,756; adolescents [aged 13-17] N = 29,093; adults [aged 18 +] N = 93,161), the proportion of patients with anxiety and depression increased from childhood to adulthood (anxiety 11.0%, 17.7%, 23.0%; depression 3.4%, 15.7%, 19.0%; anxiety and/or depression 12.9%, 25.4%, 32.2%). Compared with patients without the comorbidity profile, those with the comorbidity profile experienced a significantly higher odds of a treatment change (ORs [children, adolescents, adults] 1.37, 1.19, 1.19 for those with anxiety; 1.37, 1.30, 1.29 for those with depression; and 1.39, 1.25, 1.21 for those with anxiety and/or depression). Excess costs associated with a treatment change were generally higher with more treatment changes. Among patients with three or more treatment changes, annual excess costs per child, adolescent, and adult were $2234, $6557, and $3891 for those with anxiety; $4595, $3966, and $4997 for those with depression; and $2733, $5082, and $3483 for those with anxiety and/or depression. CONCLUSIONS: Over 12 months, patients with ADHD and comorbid anxiety and/or depression were significantly more likely to experience a treatment change than those without these psychiatric comorbidities and incurred higher excess costs with additional treatment changes.

Symptoms associated with ADHD/treatment-related adverse side effects and their impact on quality of life and work productivity in adults with ADHD.

OBJECTIVE: Describe symptoms associated with ADHD/treatment-related adverse side effects among adults with ADHD in the US and assess their impact on quality of life (QoL) and work productivity. METHODS: An online survey among adults receiving ADHD medications in the US was conducted to collect information relating to symptoms associated with ADHD/treatment-related adverse side effects. Participants were recruited from the panel of a well-established market research firm, Dynata, from 26 July to 30 July 2021 and were included in the study if they met the eligibility criteria and were willing to participate in the survey. Correlations between symptoms and key outcomes (QoL/employment/work impairment) were estimated using linear regression analyses. RESULTS: Of 585 participants, 95.2% experienced ≥1 symptom associated with ADHD/treatment-related adverse side effects in the past month (average = 5.8 symptoms). The number of symptoms was significantly correlated with reduced QoL, reduced probability of being employed, and increased work/activity impairment. Among subgroups with insomnia/other sleep disturbances and emotional impulsivity/mood lability, 50.4% and 44.7% reported their symptoms had "a lot" or "extremely" negative impact on their overall well-being, respectively. CONCLUSIONS: Symptoms associated with ADHD/treatment-related adverse side effects are common and have a substantial negative impact on QoL and reduces patients' probability of employment. Improved management of ADHD/treatment-related adverse side effects and more tolerable treatment options have the potential to improve QoL and work productivity among adults with ADHD.

Reasons for Treatment Changes in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Chart Review Study.

INTRODUCTION: This study aimed to examine the reasons underlying treatment changes among pediatric patients with attention-deficit/hyperactivity disorder (ADHD). METHODS: Data were obtained through online medical chart abstraction (08/2021-09/2021). Eligible patients with ADHD had initiated a treatment regimen at ages 6-17 and within 1-5 years of chart abstraction. Reasons contributing to treatment changes were analyzed for a randomly selected treatment episode. ADHD/treatment-related complication rate was also described. Results were reported overall and among children (ages 6-12) and adolescents (ages 13-17), separately. Physicians' perspective on adherence among their child, adolescent, and adult patients was assessed through an online survey. RESULTS: A total of 156 physicians abstracted 434 patient charts (235 children + 199 adolescents). Mean patient age was 11.3 years, and 68.7% were male. Inadequate/suboptimal symptom management was the most common reason for treatment discontinuation (50/83 [60.2%]), add-on (17/21 [81.0%]), and dose increase (189/237 [79.7%]). Patient/parent/family attitude/dislike of medication and ADHD/treatment-related complications were common reasons for treatment discontinuation, add-on, switch, and dose decrease. Overall, 42.4% of patients had ≥ 1 documented ADHD/treatment-related complication, insomnia/sleep disturbances being the most common (9.7%). Among patients with ≥ 1 complication, 75.5% reported the experience/fear of complications had a negative impact on their treatment adherence. Results were similar among children and adolescents. Physicians reported taking actions toward patients' non-adherence by further educating patients, closer monitoring, and changing the prescribed ADHD medication. CONCLUSION: Lack of effectiveness and ADHD/treatment-related complications are important reasons for treatment changes among children and adolescents with ADHD, highlighting the need for more effective and tolerable treatments to mitigate the burden of ADHD.

Identifying individuals with undiagnosed post-traumatic stress disorder in a large United States civilian population - a machine learning approach.

BACKGROUND: The proportion of patients with post-traumatic stress disorder (PTSD) that remain undiagnosed may be substantial. Without an accurate diagnosis, these patients may lack PTSD-targeted treatments and experience adverse health outcomes. This study used a machine learning approach to identify and describe civilian patients likely to have undiagnosed PTSD in the US commercial population. METHODS: The IBM® MarketScan® Commercial Subset (10/01/2015-12/31/2018) was used. A random forest machine learning model was developed and trained to differentiate between patients with and without PTSD using non-trauma-based features. The model was applied to patients for whom PTSD status could not be confirmed to identify individuals likely and unlikely to have undiagnosed PTSD. Patient characteristics, symptoms and complications potentially related to PTSD, treatments received, healthcare costs, and healthcare resource utilization were described separately for patients with PTSD (Actual Positive PTSD cohort), patients likely to have PTSD (Likely PTSD cohort), and patients without PTSD (Without PTSD cohort). RESULTS: A total of 44,342 patients were classified in the Actual Positive PTSD cohort, 5683 in the Likely PTSD cohort, and 2,074,471 in the Without PTSD cohort. While several symptoms/comorbidities were similar between the Actual Positive and Likely PTSD cohorts, others, including depression and anxiety disorders, suicidal thoughts/actions, and substance use, were more common in the Likely PTSD cohort, suggesting that certain symptoms may be exacerbated among those without a formal diagnosis. Mean per-patient-per-6-month healthcare costs were similar between the Actual Positive and Likely PTSD cohorts ($11,156 and $11,723) and were higher than those of the Without PTSD cohort ($3616); however, cost drivers differed between cohorts, with the Likely PTSD cohort experiencing more inpatient admissions and less outpatient visits than the Actual Positive PTSD cohort. CONCLUSIONS: These findings suggest that the lack of a PTSD diagnosis and targeted management of PTSD may result in a greater burden among undiagnosed patients and highlights the need for increased awareness of PTSD in clinical practice and among the civilian population.

Treatment patterns among children and adolescents with attention-deficit/hyperactivity disorder in the United States - a retrospective claims analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder affecting approximately 10.0% of children and 6.5% of adolescents in the United States (US). A comprehensive assessment of the current treatment landscape is warranted to highlight potential unmet needs of children and adolescents with ADHD. Therefore, this study described treatment patterns and healthcare costs among commercially insured children and adolescents with ADHD in the US. METHODS: Children and adolescents with ADHD initiating pharmacological treatment indicated for ADHD were identified from IBM MarketScan Commercial Database (2014-2018). A treatment sequence algorithm was used to examine treatment patterns, including discontinuation (≥ 180 days following the last day of supply of any ADHD treatment), switch, add-on, and drop (discontinuation of an agent in combination therapy), during the 12-month study period following the index date (i.e., first observed ADHD treatment). Total adjusted annual healthcare costs were compared between patients with and without treatment changes. RESULTS: Among 49,756 children and 29,093 adolescents included, mean age was 9 and 15 years, respectively, and 31% and 38% were female. As the first treatment regimen observed, 92% of both children and adolescents initiated a stimulant and 11% initiated combination therapy. Over half of the population had a treatment change over 12 months-59% of children and 68% of adolescents. Treatment discontinuation over 12 months was common in both populations-21% of children and 36% of adolescents discontinued treatment. Healthcare costs increased with the number of treatment changes observed; children and adolescents with treatment changes (i.e., 1, 2, or ≥ 3) incurred an incremental annual cost of up to $1,443 and $2,705, respectively, compared to those without a treatment change (p < 0.001). Costs were largely driven by outpatient visits. CONCLUSIONS: Over a 12-month period, treatment changes were commonly observed and were associated with excess costs, highlighting the unmet treatment needs of children and adolescents with ADHD in the US.

The Impact of Agitation in Dementia on Caregivers: A Real-World Survey.

BACKGROUND: Dementia patients frequently depend on caregivers. Agitation is a common behavioral dementia symptom particularly burdensome to patients and caregivers. OBJECTIVE: To assess the association of agitation severity with non-professional caregiver hours, burden, health status, and productivity. Secondarily, to assess the association of agitation severity with these outcomes for patients receiving remote (not living with the patient) and proximate (living with the patient) caregiving. METHODS: A retrospective analysis of physician and non-professional caregiver-reported data from a US point-in-time survey. Patients were aged ≥50 years, with early cognitive impairment or dementia. Regression analyses compared outcomes by agitation severity; covariates included age, sex, and clinical characteristics. RESULTS: Data were included for 1,349 patients (non-agitated n = 656, agitated n = 693; no care n = 305, remote care n = 248, proximate care n = 691; unknown care n = 105). Greater agitation was significantly associated (p < 0.05) in all caregivers with increasing: Zarit Burden Interview (ZBI) Total Caregiver Burden, Personal Strain, Role Strain, and Guilt; Work Productivity and Activity Index (WPAI) presenteeism, overall work impairment, and total activity impairment. Higher ZBI Total Caregiver Burden, Personal Strain, and Role Strain were associated with greater agitation in proximate caregivers and higher ZBI Guilt associated with greater agitation in remote caregivers (p < 0.05). Higher WPAI presenteeism and total activity impairment were associated (p < 0.05) with greater agitation in proximate caregivers. Caregiving hours increased with increasing agitation for proximate caregiving (p = 0.001). CONCLUSION: Greater agitation severity was associated with higher caregiver burden and lower productivity, with higher indirect costs a likely outcome of agitation.

Reasons for treatment changes in adults with attention-deficit/hyperactivity disorder: a chart review study.

BACKGROUND: Adults with attention-deficit hyperactivity disorder (ADHD) often cycle through multiple treatments for reasons that are not well documented. This study analyzed the reasons underlying treatment changes among adults treated for ADHD in a real-world setting. METHODS: Data were collected via an online reporting form completed by eligible physicians between October and November 2020. Data for adult patients in the United States who were diagnosed with ADHD and initiated a treatment regimen within 1 to 5 years of chart abstraction were obtained. Reason for a treatment change was described for a randomly selected regimen episode, which spanned from treatment initiation until the earliest among treatment add-on/switch or discontinuation, death, or date of chart abstraction. The overall rate of ADHD/treatment-related complications were also described. Physician satisfaction with current treatment options for adult ADHD and opinions on areas for improvement were assessed. RESULTS: Data on 320 patients were reported by 152 physicians specializing in psychiatry (40.1%), pediatrics (25.0%), family medicine (21.7%), and internal medicine (13.2%). Patients had a mean age of 29.3 years; most were diagnosed with ADHD as adults (57.5%) and within the previous 5 years (56.5%). Selected treatment regimens included stimulants (79.1%), nonstimulants (14.7%), and combination therapy (5.6%) for an average duration of 1.9 years. Among patients with treatment discontinuation (N = 59), the most common reasons for discontinuation were suboptimal symptom management (55.9%), occurrence of ADHD/treatment-related complications (25.4%), and patient attitude/dislike of medication (25.4%). The main reasons for other key treatment changes were inadequate/suboptimal management of symptoms and cost considerations. Over 40% of patients had ≥ 1 documented ADHD/treatment-related complication, irrespective of whether they led to a treatment change. One in 5 physicians (19.8%) were very dissatisfied, moderately dissatisfied, or neither satisfied nor dissatisfied with current treatment options for ADHD in adults; the top 3 suggested improvements were lower risk of abuse (71.7%), longer effect duration (65.1%), and fewer ADHD/treatment-related complications (61.2%). CONCLUSIONS: The top reasons for treatment changes among adults with ADHD are lack of efficacy and ADHD/treatment-related complications, highlighting the importance of developing more effective and safer treatments to alleviate the burden of ADHD.

The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective.

Objective: To estimate the economic burden of posttraumatic stress disorder (PTSD) in the United States civilian and military populations from a societal perspective.Methods: A prevalence-based and human capital approach was used to estimate the total excess costs of PTSD in 2018 from insurance claims data, academic literature, and governmental publications. Excess direct health care costs (pharmacy, medical), direct non-health care costs (research and training, substance use, psychotherapy, homelessness, disability), and indirect costs (unemployment, productivity loss, caregiving, premature mortality) associated with PTSD were compared between adults with PTSD and adults without PTSD, or the general population if information was not available for adults without PTSD.Results: The total excess economic burden of PTSD in the US was estimated at $232.2 billion for 2018 ($19,630 per individual with PTSD). Total excess costs were $189.5 billion (81.6%) in the civilian population and $42.7 billion (18.4%) in the military population, corresponding to $18,640 and $25,684 per individual with PTSD in the civilian and military populations, respectively. In the civilian population, the excess burden was driven by direct health care ($66.0 billion) and unemployment ($42.7 billion) costs. In the military population, the excess burden was driven by disability ($17.8 billion) and direct health care ($10.1 billion) costs.Conclusions: The economic burden of PTSD goes beyond direct health care costs and has been found to rival costs for other costly mental health conditions. Increased awareness of PTSD, development of more effective therapies, and expansion of evidence-based interventions may be warranted to reduce the large clinical and economic burden of PTSD.

Economic burden of attention-deficit/hyperactivity disorder among children and adolescents in the United States: a societal perspective.

OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with attention-deficit/hyperactivity disorder (ADHD) among children and adolescents from a US societal perspective. MATERIALS AND METHODS: Direct healthcare costs of children (5-11 years) and adolescents (12-17 years) with ADHD were obtained using claims data from the IBM MarketScan Research Databases (01/01/2017-12/31/2018). Direct non-healthcare and indirect costs were estimated based on literature and government publications. Each cost component was estimated using a prevalence-based approach, with per-patient costs extrapolated to the national level. RESULTS: The total annual societal excess costs associated with ADHD were estimated at $19.4 billion among children ($6,799 per child) and $13.8 billion among adolescents ($8,349 per adolescent). Education costs contributed to approximately half of the total excess costs in both populations ($11.6 billion [59.9%] in children; $6.7 billion [48.8%] in adolescents). Other major contributors to the overall burden were direct healthcare costs ($5.0 billion [25.9%] in children; $4.0 billion [29.0%] in adolescents) and caregiving costs ($2.7 billion [14.1%] in children; $1.6 billion [11.5%] in adolescents). LIMITATIONS: Cost estimates were calculated based on available literature and/or governmental publications due to the absence of a single data source for all costs associated with ADHD. Thus, the quality of cost estimates is limited by the accuracy of available data as well as the study populations and methodologies used by different studies. CONCLUSION: ADHD in children and adolescents is associated with a substantial economic burden that is largely driven by education costs, followed by direct healthcare costs and caregiver costs. Improved intervention strategies and policies may reduce the clinical and economic burden of ADHD in these populations.

Economic burden of attention-deficit/hyperactivity disorder among adults in the United States: a societal perspective.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial clinical burden as individuals transition to adulthood, including higher rates of comorbidities, mortality, incarceration, and psychiatric hospitalizations than in individuals without ADHD. These higher rates likely contribute to substantial economic burden as well. OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with ADHD in the US adult population. METHODS: Direct health care costs were obtained by using claims data from the IBM MarketScan Research Databases (January 1, 2017, through December 31, 2018). Direct non-health care costs and indirect costs were estimated on the basis of the literature and government publications. Excess costs incurred by adults with ADHD during 2018 were evaluated from a societal perspective; per-patient costs were extrapolated to the national level. RESULTS: An estimated 8.7 million adults live with ADHD in the United States, resulting in a total societal excess cost attributable to ADHD of $122.8 billion ($14,092 per adult). Excess costs of unemployment ($66.8 billion; 54.4%) comprised the largest proportion of the total, followed by productivity loss ($28.8 billion; 23.4%) and health care services ($14.3 billion; 11.6%). CONCLUSIONS: ADHD in adults is associated with substantial economic burden. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka). The study sponsor contributed to and approved the study design, participated in the interpretation of data, and reviewed and approved the manuscript. Schein is an employee of Otsuka. Gagnon-Sanschagrin, Davidson, Kinkead, Cloutier, Guérin, and Lefebvre are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Otsuka to develop and conduct this study and write the manuscript. Adler has received research support from Shire/Takeda, Sunovion, and Otsuka; consulting fees from Bracket, Shire/Takeda, Sunovion, Otsuka, the State University of New York (SUNY), the National Football League (NFL), and Major League Baseball (MLB); and royalty payments (as inventor) from New York University (NYU) for license of adult ADHD scales and training materials. Childress has received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the US Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, and Tulex Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. Part of the material in this study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 Virtual Meeting; May 17-20, 2021.

Treatment patterns among adults with attention-deficit/hyperactivity disorder in the United States: a retrospective claims study.

OBJECTIVE: To assess treatment patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and associated healthcare costs in a real-world US setting. METHODS: Claims data from the IBM MarketScan Commercial Subset (Q1/2014-Q4/2018) was used to identify adults diagnosed with ADHD who newly initiated on ADHD treatment (index date). Treatment sequences were defined using an algorithm; for each sequence, the regimen comprised all ADHD-related agents observed within 30 d of the first agent during the 12-month study period. Treatment changes included discontinuation, switch, add-on, and drop. Treatment characteristics were described for the first treatment regimen observed. Total adjusted annual healthcare costs were compared between patients with no treatment change and patients with 1, 2, and ≥3 treatment changes. RESULTS: Among 122,881 adults with ADHD, the majority initiated a stimulant (95.1%) as their first treatment regimen observed; 9.3% of patients initiated combination therapy of ≥2 ADHD-related agents, and 34.9% of patients had psychotherapy. After an average first treatment regimen duration of 7.1 months, 50.2% of patients experienced a treatment change (22.5% discontinued, 17.5% switched, 5.3% had an add-on, and 4.6% had a treatment drop). Among those who discontinued, 44.8% did so within the first month of initiation. Mean annual healthcare costs were higher among patients with at least 1 treatment change compared to those with no treatment changes; excess costs increased with each additional treatment change. CONCLUSIONS: Treatment changes were commonly observed and were associated with excess healthcare cost, emphasizing the unmet treatment needs of adults with ADHD in the US.

Direct Costs of Opioid Abuse in an Insured Population in the United States.

OBJECTIVE: To (a) describe the demographics of opioid abusers; (b) compare the prevalence rates of selected comorbidities and the medical and drug utilization patterns of opioid abusers with patients from a control group, for the period from 1998 to 2002; and (c) calculate the mean annual per-patient total health care costs (e.g., inpatient, outpatient, emergency room, drug, other) from the perspective of a private payer. METHODS: An administrative database of medical and pharmacy claims from 1998 to 2002 of 16 self-insured employer health plans with approximately 2 million lives was used to identify "opioid abusers"-patients with claims associated with ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes for opioid abuse (304.0, 304.7, 305.5, and 965.0 [excluding 965.01]). A control group of nonabusers was selected using a matched sample (by age, gender, employment status, and census region) in a 3:1 ratio. Per-patient annual health care costs (mean total medical and drug costs) were measured in 2003 U.S. dollars. Multivariate regression techniques were also used to control for comorbidities and to compare costs with a benchmark of depressed patients. RESULTS: 740 patients were identified as opioid abusers, a prevalence of 8 in 10,000 persons aged 12 to 64 years continuously enrolled in health care plans for whom 12 months of data were available for calculating costs. Opioid abusers, compared with nonabusers, had significantly higher prevalence rates for a number of specific comorbidities, including nonopioid poisoning, hepatitis (A, B, or C), psychiatric illnesses, and pancreatitis, which were approximately 78, 36, 9, and 21 (P<0.01) times higher, respectively, compared with nonabusers. Opioid abusers also had higher levels of medical and prescription drug utilization. Almost 60% of opioid abusers had prescription drug claims for opioids compared with approximately 20% for nonabusers. Prevalence rates for hospital inpatient visits for opioid abusers were more than 12 times higher compared with nonabusers (P<0.01). Mean annual direct health care costs for opioid abusers were more than 8 times higher than for nonabusers ($15,884 versus $1,830, respectively, P < 0.01). Hospital inpatient and physician-outpatient costs accounted for 46% ($7,239) and 31% ($5,000) of opioid abusers' health care costs, compared with 17% ($310) and 50% ($906), respectively, for nonabusers. Mean drug costs for opioid abusers were more than 5 times higher than costs for nonabusers ($2,034 vs. $386, respectively, P<0.01), driven by higher drug utilization (including opioids) for opioid abusers. Even when controlling for comorbidities using a multivariate regression model of a matched control of depressed patients, the average health care costs of opioid abusers were 1.8 times higher than the average health care costs of depressed patients. CONCLUSION: The high costs of opioid abuse were driven primarily by high prevalence rates of costly comorbidites and high utilization rates of medical services and prescription drugs. DISCLOSURES: Funding for this research was provided by an unrestricted grant from Janssen Medical Affairs, L.L.C. and was obtained by authors Susan Vallow and Jeff Schein, who are employed by Janssen Medical Affairs, L.L.C. Nathaniel Katz is a consultant to Janssen and numerous other pharmaceutical companies that manufacture branded opioid products and nonopioid analgesics; authors Alan G. White, Howard G. Birnbaum, Milena N. Mareva, and Maham Daher disclose no potential bias or conflict of interest relating to this article. White served as principal author of the study. Study concept and design were contributed primarily by White, Vallow, Schein, and Katz. Analysis and interpretation of data were contributed by all authors. Drafting of the manuscript was primarily the work of White, and its critical revision was the work of White and Vallow. Statistical expertise was contributed by White, Birnbaum, and Daher, and administrative, technical, and/or material support was provided by Analysis Group, Inc., Boston, MA.

Healthcare resource utilization and costs associated with venous thromboembolism in cancer patients treated with anticoagulants.

Objective: The standard of care for cancer-related venous thromboembolism (VTE) has been low molecular weight heparin (LMWH), but oral anticoagulants are also widely prescribed. This study compared VTE-related healthcare resource utilization and costs of cancer patients treated with anticoagulants. Methods: Claims data from Humana Database (January 1, 2013-May 31, 2015) were analyzed. Based on the first anticoagulant received, patients were classified into LMWH, warfarin, or rivaroxaban cohorts. Characteristics were evaluated during the 6 months pre-index date (i.e. the first VTE); VTE-related resource utilization and costs were evaluated during follow-up. Cohorts were compared using rate ratios, and p-values and 95% confidence intervals were calculated. Healthcare costs were evaluated per-patient-per-year (PPPY) and compared using mean cost differences. Results: A total of 2,428 patients (LMWH: n = 660; warfarin: n = 1,061; rivaroxaban: n = 707) were included. Compared to patients treated with LMWH, patients treated with rivaroxaban had significantly fewer VTE-related hospitalizations, hospitalization days, and emergency room and outpatient visits, resulting in an increase of $12,000 VTE-related healthcare costs PPPY with LMWH vs rivaroxaban. Patients treated with rivaroxaban had significantly lower VTE-related resource utilization compared to patients treated with warfarin; however, VTE-related costs were similar between cohorts. The higher drug costs ($1,519) were offset by significantly lower outpatient (-$1,039) and hospitalization costs (-$522) in rivaroxaban relative to the warfarin cohort. Conclusions: Healthcare resource use and costs associated with VTE treatment in cancer patients are highest with LMWH relative to warfarin and rivaroxaban.

Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants.

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE (n = 1,340) and those with MB (n = 3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively (p < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively (p < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

Duration of anticoagulant therapy and VTE recurrence in patients with cancer.

PURPOSE: Anticoagulant therapy for at least 3-6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer, but the optimal duration of treatment is unknown. This study examines the association between the duration of anticoagulation treatment and VTE recurrence in cancer patients. METHODS: The Humana claims database was used to identify newly diagnosed cancer patients who had their first VTE diagnosis between January 1, 2013, and May 31, 2015, and initiated injectable or oral anticoagulant therapy. Follow-up was calculated from the index treatment initiation to the end of eligibility or end of data (June 2015). VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE. Cox proportional hazards models were used to evaluate the risk of VTE recurrence by duration of therapy in patients who discontinued therapy. RESULTS: The study included 1158 patients. Compared to patients treated for 0 to 3 months, VTE recurrences were significantly lower among patients treated for 3 to 6, or over 6 months. After adjustment for baseline characteristics, patients treated for 3 to 6 months (HR [95%CI], 0.53; 0.37-0.76) and more than 6 months (HR [95%CI], 0.48; 0.34-0.68) were still significantly less likely to have VTE recurrences compared to patients treated for 0 to 3 months (both p < 0.01). Findings were similar using a VTE event definition that included outpatient visits. CONCLUSIONS: Among newly diagnosed cancer patients with VTE, anticoagulant therapy lasting more than 3 months was associated with a lower risk of VTE recurrence.