Economic Burden of Commercially Insured Patients With Major Depressive Disorder and Acute Suicidal Ideation or Behavior in the United States.

Objective: Suicidal ideation or behavior (SIB) is a symptom of major depressive disorder (MDD). This study evaluated health care resource utilization (HRU) and costs of commercially insured adults who had diagnosed MDD with acute SIB (MDSI).Methods: Adults with MDSI (index date: first SIB claim) and controls without MDD or suicide-related claims (random index date) were identified using International Classification of Diseases, Clinical Modification, 10th Revision codes in the OptumHealth Care Solutions, Inc. database (October 2014 to March 2017). Adults with < 12 months of plan enrollment pre-index and/or selected psychiatric comorbidities were excluded. MDSI and control cohorts were matched 1:1 on demographics and comorbidities. HRU and costs were compared between matched cohorts during up to 1 and 12 months post-index (inclusive) using regressions adjusted for baseline costs.Results: Among patients with MDSI (n = 1,576, mean age = 34 years, 55.6% female), most index events occurred in emergency department (ED; 50.7%) and inpatient (45.2%) settings. The MDSI cohort, compared with the control cohort within 1 and 12 months post-index, respectively, had 157.7 and 28.0 times more inpatient admissions, 16.4 and 5.4 times more ED visits, and 4.9 and 3.2 times more outpatient visits (all P < .01). Incremental health care costs per patient per month in the MDSI compared with the control cohort within 1 and 12 months were $7,839 and $2,757, respectively (both P values < .01). Inpatient and ED costs constituted 70.6% and 16.5% of the total incremental costs, respectively, within the first month of follow-up.Conclusions: Among commercially insured adults, MDSI was associated with significant economic burden; inpatient and ED services drove incremental costs of the condition. Further assessment of treatment options for this vulnerable patient population is warranted.

The Economic Burden of Adults with Major Depressive Disorder in the United States (2010 and 2018).

BACKGROUND: The incremental economic burden of US adults with major depressive disorder (MDD) was estimated at $US210.5 billion in 2010 (year 2012 values). OBJECTIVE: Following a similar methodology, this study updates the previous findings with more recent data to report the economic burden of adults with MDD in 2018. METHOD: This study used a framework for evaluating the incremental economic burden of adults with MDD in the USA that combined original and literature-based estimates, focusing on key changes between 2010 and 2018. The prevalence rates of MDD by sex, age, employment, and treatment status over time were estimated based on the National Survey on Drug Use and Health (NSDUH). The incremental direct and workplace costs per individual with MDD were primarily derived from administrative claims data and NSDUH data using comparative analyses of individuals with and without MDD. Societal direct and workplace costs were extrapolated by multiplying NSDUH estimates of the number of people with MDD by the direct and workplace cost estimates per patient. The suicide-related costs were estimated using a human capital method. RESULTS: The number of US adults with MDD increased by 12.9%, from 15.5 to 17.5 million, between 2010 and 2018, whereas the proportion of adults with MDD aged 18-34 years increased from 34.6 to 47.5%. Over this period, the incremental economic burden of adults with MDD increased by 37.9% from $US236.6 billion to 326.2 billion (year 2020 values). All components of the incremental economic burden increased (i.e., direct costs, suicide-related costs, and workplace costs), with the largest growth observed in workplace costs, at 73.2%. Consequently, the composition of 2018 costs changed meaningfully, with 35% attributable to direct costs (47% in 2010), 4% to suicide-related costs (5% in 2010), and 61% to workplace costs (48% in 2010). This increase in the workplace cost share was consistent with more favorable employment conditions for those with MDD. Finally, the proportion of total costs attributable to MDD itself as opposed to comorbid conditions remained stable at 37% (38% in 2010). CONCLUSION: Workplace costs accounted for the largest portion of the growing economic burden of MDD as this population trended younger and was increasingly likely to be employed. Although the total number of adults with MDD increased from 2010 to 2018, the incremental direct cost per individual declined. At the same time, the proportion of adults with MDD who received treatment remained stable over the past decade, suggesting that substantial unmet treatment needs remain in this population. Further research is warranted into the availability, composition, and quality of MDD treatment services.

Correction: Burden of treatment-resistant depression in Medicare: A retrospective claims database analysis.

[This corrects the article DOI: 10.1371/journal.pone.0223255.].

Healthcare resource utilization and costs associated with postpartum depression among commercially insured households.

OBJECTIVE: To quantify the economic burden of postpartum depression (PPD) that accrues to commercially insured households in the year following childbirth. METHODS: Administrative claims data from OptumHealth Care Solutions (2009-2016) were used to identify households that included women identified with PPD per the algorithm and propensity score-matched comparison households of women who were not identified with PPD or a history of depression after childbirth. Study outcomes included direct total all-cause medical and pharmaceutical costs during the first year following childbirth and number of outpatient visits at the household level stratified by household member. RESULTS: Households affected by PPD as identified by the algorithm (N = 7769) incurred 22% higher mean total all-cause medical and pharmaceutical spending than unaffected matched controls (N = 41,308) during the first year following childbirth ($36,049 versus $29,448, p < 0.01) and an average of 16 more outpatient visits than unaffected households (p < .01). Costs accrued by mothers comprised the largest share (>50%) of total all-cause spending. Mothers identified with PPD had significantly higher annual mean direct total all-cause medical and pharmaceutical spending than their matched controls without PPD ($19,611 versus $15,410, p < .01), driven primarily by an average of 11 more outpatient visits than unaffected mothers (p < .01). CONCLUSIONS: Households affected by PPD as identified by the algorithm incurred higher mean total all-cause medical and pharmaceutical spending during the first year following childbirth than did their matched controls identified without PPD, but not all costs were attributable to maternal treatment for PPD. These findings contribute to a better understanding of the potential economic burden associated with PPD and demonstrated costs may extend beyond the mother to members of the household.

Burden of treatment-resistant depression in Medicare: A retrospective claims database analysis.

BACKGROUND: Previous studies have assessed the incremental economic burden of treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder (i.e., non-TRD MDD) in commercially-insured and Medicaid-insured patients, but none have focused on Medicare-insured patients. OBJECTIVE: To assess healthcare resource utilization (HRU) and costs of patients with TRD versus non-TRD MDD or without major depressive disorder (MDD; i.e., non-MDD) in a Medicare-insured population. METHODS: Adult patients were retrospectively identified from the Chronic Condition Warehouse de-identified 100% Medicare database (01/2010-12/2016). MDD was defined as ≥1 MDD diagnosis and ≥1 claim for an antidepressant. Patients initiated on a third antidepressant following two antidepressant treatment regimens of adequate dose and duration were considered to have TRD. The index date was defined as the date of the first antidepressant claim for the TRD and non-TRD MDD cohorts, and as a randomly imputed date for the non-MDD cohort. Patients with TRD were matched 1:1 to non-TRD MDD patients and randomly selected non-MDD patients based on propensity scores. Analyses were also performed for a subset of patients aged ≥65. RESULTS: Of 29,543 patients with MDD, 3,225 (10.9%) met the study definition of TRD; 157,611 were included in the non-MDD cohort. Matched patients with TRD and non-TRD MDD were, on average, 58.9 and 59.0 years old, respectively. The TRD cohort had higher per-patient-per-year (PPPY) HRU than the non-TRD MDD (e.g., inpatient visits: incidence rate ratio [IRR] = 1.36) and non-MDD cohorts (e.g., inpatient visits: IRR = 1.84, all P<0.001). The TRD cohort had significantly higher total PPPY healthcare costs than the non-TRD MDD cohort ($25,517 vs. $20,425, adjusted cost difference = $3,385) and non-MDD cohort ($25,517 vs. $14,542, adjusted cost difference = $4,015, all P<0.001). Similar results were found for the subset of patients ≥65. CONCLUSION: Among Medicare-insured patients, those with TRD had higher HRU and costs compared to those with non-TRD MDD and non-MDD.

Medicaid spending burden among beneficiaries with treatment-resistant depression.

AIM: To evaluate Medicaid spending and healthcare resource utilization (HRU) in treatment-resistant depression (TRD). MATERIALS & METHODS: TRD beneficiaries were identified from Medicaid claims databases (January 2010-March 2017) and matched 1:1 with major depressive disorder (MDD) beneficiaries without TRD (non-TRD-MDD) and randomly selected patients without MDD (non-MDD). Differences in HRU and per-patient-per-year costs were reported in incidence rate ratios (IRRs) and cost differences (CDs), respectively. RESULTS: TRD beneficiaries had higher HRU than 1:1 matched non-TRD-MDD (e.g., inpatient visits: IRR = 1.41) and non-MDD beneficiaries (N = 14,710 per cohort; e.g., inpatient visits: IRR = 3.42, p < 0.01). TRD beneficiaries incurred greater costs versus non-TRD-MDD (CD = US$4382) and non-MDD beneficiaries (CD = US$8294; p < 0.05). CONCLUSION: TRD is associated with higher HRU and costs versus non-TRD-MDD and non-MDD. TRD poses a significant burden to Medicaid.

Direct and Indirect Cost Burden and Change of Employment Status in Treatment-Resistant Depression: A Matched-Cohort Study Using a US Commercial Claims Database.

BACKGROUND: Treatment-resistant depression (TRD) poses a substantial burden to health care payers including employers, costing an estimated $29 billion-$48 billion yearly in the United States. Furthermore, variation of burden across increasing levels of resistance and the potential impact of TRD on employment status remain largely unexplored. OBJECTIVE: To evaluate health care resource utilization (HRU) and costs, work loss, indirect costs, and employment status change in TRD. METHODS: A claims-based algorithm identified adults with TRD from a US claims database of privately insured employees and dependents (January 2010-March 2015). TRD patients were matched 1:1 on demographics to patients with major depressive disorder (MDD) (non-TRD MDD) and without MDD (non-MDD), who were identified using ICD-9-CM codes. Costs, HRU, and employment status change were compared over 2 years following the first antidepressant (randomly imputed date for non-MDD), adjusting for baseline comorbidity index and costs. RESULTS: TRD patients (N = 6,411) had more HRU than either matched control cohort, translating into higher per patient per year (PPPY) health care costs: $6,709 and $9,917 more than non-TRD MDD and non-MDD patients, respectively (P < .001 for both). TRD patients with work loss data (N = 1,908) had 35.8 work loss days PPPY (1.7 and 6.2 times the work loss rate in non-TRD MDD and non-MDD patients, respectively). Work loss-related costs in TRD patients were $1,811 higher than non-TRD MDD and $3,460 higher than in non-MDD patients (P < .001). TRD patients had 1.3-1.4 times the rate of employment status change versus control cohorts (all P < .05). CONCLUSIONS: TRD, even compared to MDD, poses a significant direct and indirect cost burden to US employers and may be associated with higher rates of employment status change.

The economic burden of adults with major depressive disorder in the United States (2005 and 2010).

BACKGROUND: The economic burden of depression in the United States--including major depressive disorder (MDD), bipolar disorder, and dysthymia--was estimated at $83.1 billion in 2000. We update these findings using recent data, focusing on MDD alone and accounting for comorbid physical and psychiatric disorders. METHOD: Using national survey (DSM-IV criteria) and administrative claims data (ICD-9 codes), we estimate the incremental economic burden of individuals with MDD as well as the share of these costs attributable to MDD, with attention to any changes that occurred between 2005 and 2010. RESULTS: The incremental economic burden of individuals with MDD increased by 21.5% (from $173.2 billion to $210.5 billion, inflation-adjusted dollars). The composition of these costs remained stable, with approximately 45% attributable to direct costs, 5% to suicide-related costs, and 50% to workplace costs. Only 38% of the total costs were due to MDD itself as opposed to comorbid conditions. CONCLUSIONS: Comorbid conditions account for the largest portion of the growing economic burden of MDD. Future research should analyze further these comorbidities as well as the relative importance of factors contributing to that growing burden. These include population growth, increase in MDD prevalence, increase in treatment cost per individual with MDD, changes in employment and treatment rates, as well as changes in the composition and quality of MDD treatment services.

Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs.

OBJECTIVE: Nonadherence is a major challenge in schizophrenia treatment. While long-acting (depot) antipsychotic medications are often recommended to address adherence problems, evidence on the comparative effectiveness of depot versus oral antipsychotics is inconsistent. We hypothesize that this inconsistency could be due to systematic differences in study design. This review evaluates the effect of study design on the comparative effectiveness of antipsychotic formulations. The optimal use of different antipsychotic formulations in a general clinical setting depends on better understanding of the underlying reasons for differences in effectiveness across research designs. DATA SOURCES: A PubMed literature review targeted English-language studies (2000-2011) with information on relapse, hospitalization, or all-cause discontinuation for depot and oral antipsychotic treatment arms in schizophrenia. The time frame was chosen to reflect research focused on the newer generation of antipsychotic agents. The search required at least 1 term from each of the following categories: (1) schizophrenia; (2) inject, injection, injectable, injectables, injected, depot, long-acting; and (3) iloperidone, fluphenazine, haloperidol, paliperidone, risperidone, olanzapine, asenapine, flupentixol, flupenthixol, lurasidone, clopenthixol, fluspirilene, zuclopentixol, zuclopenthixol. STUDY SELECTION: Thirteen relevant studies were identified by 2 independent reviewers; these studies included information on 19 depot-oral comparisons. DATA EXTRACTION: Age- and gender-adjusted risk ratios (RRs) (depot/oral) were calculated for the identified endpoints and pooled by study design (randomized controlled trial [RCT], prospective observational, and retrospective observational). Meta-analysis with random effects was used to estimate the pooled RRs, by study design. Average conversion factors between study designs were calculated as the ratios of pooled RRs. RESULTS: Meta-analysis of adjusted endpoints showed no apparent benefit of depot over oral formulations in RCTs, with an RR of 0.89 (P = .416). In contrast, there was a significant advantage for depot formulations in other study designs (prospective RR = 0.62 [P < .001]; retrospective RR = 0.56 [P < .001]). These imply conversion factors of 1.43 and 1.59 between RCTs and prospective and retrospective designs, respectively. CONCLUSIONS: The comparative effectiveness of antipsychotic formulations is sensitive to research design. Depot formulations displayed significant advantages in nonrandomized observational studies, whereas in RCTs no difference was observed. The estimated conversion factors may facilitate comparison across studies.

Comparing treatment persistence, healthcare resource utilization, and costs in adult patients with major depressive disorder treated with escitalopram or citalopram.

BACKGROUND: Major depressive disorder is the most common type of depression, affecting 6.6% of adults in the United States annually. Citalopram and escitalopram are common second-generation antidepressants used for the treatment of patients with this disorder. Because citalopram is available in generic forms that have lower acquisition costs compared with the branded escitalopram, some health plans may provide incentives to encourage the use of the generic option. Decisions based solely on drug acquisition costs may encourage the use of a therapy that is less cost-effective when treatment persistence, healthcare utilization, and overall costs are factored in. OBJECTIVE: To compare, in a real-world setting, the treatment persistence, healthcare utilization, and overall costs of managing adult patients with major depressive disorder who are treated with escitalopram or citalopram. METHODS: Administrative claims data (from January 1, 2003, to June 30, 2005) were analyzed for patients with major depressive disorder aged ≥18 years. Patients filled ≥1 prescriptions for citalopram or for escitalopram (first-fill time was defined as the index date) and had no second-generation antidepressant use during the 6-month preindex period. Treatment persistence, healthcare utilization, and healthcare costs were measured over the 6-month preindex and 6-month postindex periods and compared between patients treated with citalopram or escitalopram, using unadjusted and multivariate analyses. RESULTS: Patients receiving escitalopram (N = 10,465) were less likely to discontinue the treatment (hazard ratio 0.94; P = .005) and switch to another second-generation antidepressant (hazard ratio 0.83; P <.001) than patients receiving citalopram (N = 4212). Patients receiving escitalopram were also less likely to have a hospital admission (odds ratio 0.88; P = .036) or an emergency department visit and had lower total healthcare costs (-$1174) and major depressive disorder-related costs (-$109; P <.001) during the study period. CONCLUSION: Although the drug acquisition costs are lower for generic citalopram than for the brand-name escitalopram, patients treated with escitalopram had better treatment persistence, lower healthcare utilization, and lower overall costs compared with patients treated with citalopram over the study period. This may suggest that other considerations, in addition to acquisition cost, may need to be factored in to assess the cost-effectiveness of drug therapy.

Risk of hepatotoxicity-related hospitalizations among patients treated with opioid/acetaminophen combination prescription pain medications.

OBJECTIVE: This study determined the risk of serious hepatotoxicity resulting in hospitalizations among patients prescribed opioid/acetaminophen combinations. METHODS: A retrospective cohort study using an insurance claims database was conducted. Adult patients with ≥1 claim for oxycodone/acetaminophen or hydrocodone/acetaminophen combinations were included (N = 1,228,356). A pre-post design was employed to compare serious hepatotoxicity risk before versus after initiation of opioid/acetaminophen combination. Serious hepatotoxicity risk between the opioid/acetaminophen group and a control group of opioid-alone users (N = 11,809) was also examined. Within the opioid/acetaminophen group, risk of hepatotoxicity-related hospitalizations pre- versus post-opioid/acetaminophen treatment was compared using the normal approximation with the binomial distribution. The incidence rate of hepatotoxicity-related hospitalizations for the opioid/acetaminophen group was compared with the opioid-alone group using multivariate Poisson regression adjusting for baseline differences between groups. RESULTS: Of the opioid/acetaminophen cohort, hepatotoxicity-related hospitalization risk in the 6-month post-opioid/acetaminophen period was lower than that in the pre-period with a risk reduction of 1.2 per 10,000 (pre-period = 0.12%; 95% confidence interval [CI], 0.12 to 0.13; post-period = 0.11%; 95% CI, 0.11 to 0.12). In the 12-month period, risk increased in the post-period by 2.4 per 10,000 (pre-period = 0.14%; 95% CI, 0.14 to 0.15; post-period = 0.17%; 95% CI, 0.16 to 0.18). After adjusting for confounders, the opioid-alone group did not demonstrate a lower rate of hepatotoxicity-related hospitalizations than the opioid/acetaminophen group (incidence rate ratio of opioid-alone over opioid/acetaminophen = 2.9; 95% CI, 1.8 to 4.7). CONCLUSIONS: There is no population data-based evidence supporting elevated risk of hepatotoxicity-related hospitalization associated with opioid/acetaminophen combinations.

Assessing the relationship between compliance with antidepressant therapy and employer costs among employees in the United States.

OBJECTIVE: To assess effects of antidepressant treatment compliance on health care and workplace costs. METHODS: By using workplace survey data linked to two employers' health care claims, employees with depression/antidepressant claims were categorized into noncompliant/compliant groups. Annualized costs were compared between compliance groups, for the employees with antidepressant use and a subset diagnosed with depression. RESULTS: Among antidepressant users (N = 1224), medical costs were not statistically different for compliant versus noncompliant patients; drug costs were higher for compliant patients, primarily because of antidepressants' costs. Similar associations were observed among depressed patients (N = 488). Absenteeism costs were lower for compliant patients with antidepressant use ($3857 vs $4,907, P = 0.041) and among depressed patients ($3976 vs $5899, P = 0.047). Presenteeism costs were higher for depressed compliant patients ($19,170 vs $15,829, P = 0.011). CONCLUSIONS: Increased compliance with antidepressants is significantly associated with reduced absenteeism costs.

Employer burden of mild, moderate, and severe major depressive disorder: mental health services utilization and costs, and work performance.

BACKGROUND: Treatment utilization/costs and work performance for persons with major depressive disorder (MDD) by severity of illness is not well documented. METHODS: Using National Comorbidity Survey-Replication (2001-2002) data, US workforce respondents (n=4,465) were classified by clinical severity (not clinically depressed, mild, moderate, severe) using a standard self-rating scale [Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)]. Outcomes included 12-month prevalence of medical services/medications use/costs and workplace performance. Treatment costs (employer's perspective) were estimated by weighing utilization measures by unit costs obtained for similar services used by MDD patients in claims data. Descriptive analysis across three severity groups generated chi(2) results. RESULTS: Using a sample of 539 US workforce respondents with MDD, 13.8% were classified mild, 38.5% moderate, and 47.7% severe cases. Mental health services usage, including antidepressants, increased significantly with severity, with average treatment costs substantially higher for severe than for mild cases both regarding mental health services ($697 vs. $388, chi(2)=4.4, P=.019) and antidepressants ($256 vs. $88, chi(2)=9.0, P=.001). Prevalence rates of unemployment/disability increased significantly (chi(2)=11.7, P=.003) with MDD severity (15.7, 23.3, and 31.3% for mild, moderate, and severe cases). Severely and moderately depressed workers missed more work than nondepressed workers; the monthly salary-equivalent lost performance of $199 (severely depressed) and $188 (moderately depressed) was significantly higher than for nondepressed workers (chi(2)=10.3, P<.001). Projected to the US workforce, monthly depression-related worker productivity losses had human capital costs of nearly $2 billion. CONCLUSIONS: MDD severity is significantly associated with increased treatment usage/costs, treatment adequacy, unemployment, and disability and with reduced work performance.

The economic implications of generic substitution of antiepileptic drugs: a review of recent evidence.

BACKGROUND: The US Food and Drug Administration (FDA) considers generic and branded drugs to be therapeutically equivalent if they are pharmaceutically equivalent and bioequivalent. The American Academy of Neurology (AAN) disagrees and opposes generic substitution of branded antiepileptic drugs (AEDs) without physician and patient approval due to the risk of loss of seizure control. OBJECTIVE: To review the evidence to date surrounding the economic impact of brand-to-generic substitutions of AEDs. METHODS: A systematic search of PubMed and MEDLINE was conducted; the bibliographies of key articles obtained from the search were used to identify additional sources. RESULTS/CONCLUSION: Current literature suggests statistically higher overall healthcare costs during periods of generic AED use than during periods when branded AED are used, consistently demonstrated across different countries (Canada and the USA) and in both stable and unstable epilepsy patients, with more pronounced cost increases in patients receiving multiple generic versions. Brand-to-generic substitutions of AEDs do not necessarily reduce overall healthcare costs and may even increase them.