Table 1.
Overview of the studies selected for this review (those that provide empirical and explicit information on adherence measurements and health care costs), ordered by date of publication
| Study | Objective/s | Design | Methods/outcome measures | Results and conclusions |
|---|---|---|---|---|
| MarketScan database USA (Peng et al)25 | Determine change in hospitalization risk from 6 months pre- to 6 months post-initiation on any LAI antipsychotic. Determine changes in the utilization of outpatient services, patients’ adherence level, and total direct costs and cost components |
Mirror-image study, with evaluation of treatment periods lasting 12 months (6 months before and 6 months after starting treatment with LAI antipsychotics); information retrieved from a claims database | “Adherence” to antipsychotic medication, defined through the MPR; number of psychiatric hospital admissions; utilization of outpatient services (emergency room, day treatment and other outpatient visits); and total direct health care costs and selected cost components | N = 147; significant increase from 36.8% to 60.3% in MPR and decrease from 49.7% to 22.4% in the proportion of patients hospitalized for any psychiatric reason and the mean number of hospitalizations for schizophrenia from 0.53 to 0.29 after LAI initiation; decrease in mean (median) total direct costs from US$11,111.30 (US$7089.40) to US$7883.80 (US$4051.93) per patient, driven by reductions in psychiatric hospitalizations. In conclusion, there were declines in hospitalization rates and related costs after initiating LAI therapy |
| LAI risperidone in New Zealand (Carswell et al)26 | Explore costs of patients treated with LAI risperidone in New Zealand | Mirror-image (12 months pre- and 12 months post-initiation of LAI risperidone); data collected retrospectively from medical files, with cases ascertained through consulting an anonymous list of prescription approvals for LAI risperidone | “Nonadherence,” defined as any break in treatment recorded in the medical files during the follow-up period; number of admissions; length of bed stay; treatment data (risperidone LAI and all other antipsychotic medication, total daily dose, and route of administration); hospitalization costs associated with the use of LAI risperidone (cost per admission and per hospital day) | N = 443; decrease (from pre- to post-LAI risperidone period) in hospitalization costs by approximately NZ$1.7 million (when computed as cost per admission), increase in hospitalization costs by approximately NZ$3.5 million (when computed as cost per day spent in hospital); lower mean number of admissions (1.38 vs 0.61) but greater mean length of bed stay (37.2 vs 53.3 days); patients who remained on LAI risperidone 12 months after initiation had fewer admissions and smaller increases in days in hospital (increase from 38.4 to 41.8 days) than patients who discontinued LAI risperidone use in the first year (increase from 38.4 to 69.5 days). In conclusion, longer admissions were driven by those who discontinued treatment within 12 months and improved resource and cost outcomes are associated with continuation |
| California Medicaid (Medi-Cal) adapted to the US Medicaid (Marcus and Olfson)27 | Estimate the fraction of hospital admission and hospital days attributable to gaps in antipsychotic medication in California, in patients covered by Medi-Cal, derive the US national number and cost of acute care impatient admissions that are attributable to gaps in antipsychotic medication | Retrospectively collated information from the databases of two surveys and Medicaid prescription claims of patients treated with oral antipsychotics | “Nonadherence,” defined as gaps in antipsychotic coverage calculated from prescription claims; rate of inpatient admission per 100,000 eligible person-days; number of hospital admissions and inpatient days attributable to medication nonadherence; number of Medicaid-reimbursed acute care hospital admissions for schizophrenia; national number of inpatient days attributable to medication nonadherence; daily costs of inpatient hospitalization, taken from a survey of Medicare unit costs | N = 35,815, accounting for 1208 inpatient admissions, with 4.44 inpatient schizophrenia admissions per 100,000 person-days; 36.6% of inpatient admissions occurred within medication gaps, which were associated independently with a significant increase in the odds of admission (OR = 1.49); 12.3% (with 15-day gaps) and 9.5% (30-day gaps) of acute care inpatient admissions attributable to not receiving antipsychotic medication; the calculated national cost savings of these fractions was US$106 million per year. In conclusion, gaps in antipsychotic medication treatment appear to significantly contribute to the national costs of acute care inpatient of schizophrenia patients, thus enhancement of the continuity of antipsychotic treatment has the potential to lead to savings |
| Florida Medicaid recipients (Becker et al)28 | Compare medication adherence, service costs, and other outcomes among persons taking different classes of antipsychotic medication | Retrospectively collated information from a Medicaid prescription claims database of patients treated with antipsychotics and databases of other publicly funded behavioral health services | Four adherence levels, based on the proportion of prescriptions filled: (1) maximal adherence (75%–100% use over the 2-year study), (2) moderate adherence (50%–74.9%), (3) minimal adherence (25%–49.9%), and (4) negligible adherence (<25%); direct cost of health care services, including pharmacy, covered by Medicaid and other publicly funded behavioral health services | N = 10,330; inverse and significant relationship between health care costs and the level of adherence: lower resource utilization, to a mean calculated value of US$729 (if treated with FGA) and US$1189 (if treated with SGA) per patient per month by patients in the maximal adherence level (64% of the sample), compared with US$1102 (patients of FGA) and US$1238 (patients on SGA) by patients in the minimal adherence level (18.8% of the sample), and US$1023 (FGA) and US$1322 (SGA) by patients in the negligible adherence level (4.9% of the sample). In conclusion, treatment adherence is a key factor in the relationship between a physician’s drug treatment plan and a patient outcome; it may be as important to treatment costs and benefits as the class of medication used |
| San Diego Medicaid recipients (Gilmer et al)9 | Assess the level of antipsychotic medication adherence; examine the risk factors associated with nonadherence; examine the relationship of nonadherence to hospitalizations and health care costs | Retrospectively collated information from a claims database of Medicaid patients treated with oral antipsychotics, using patient-years of follow-up as the unit of analysis | “Nonadherence” defined as MPR between 0 and 0.49, partial adherence as MPR between 0.50 and 0.79, adherence between 0.80 and 1.10, and excess filling as MPR > 1.10; the annual cumulative MPR was calculated from prescription claims; number of medical and psychiatric hospitalizations; amount paid by Medicaid for inpatient, outpatient medical and mental health, and acute care | Data available from 2801 person-years; 24% of patients categorized as nonadherent, 16% partially adherent, 19% excess fillers, and 41% adherent; adherence generally increased with age; substance abusers and homeless patients were likely to be nonadherent. Nonadherent patients were 2.5 times more likely, and excess fillers or partially adherent patients 80% more likely, to be hospitalized for psychiatric reasons than adherent patients; mean yearly hospital expenditures of nonadherent patients (US$3413 per patient) were three times higher than the expenditures of adherent patients (US$1025 per patient), as were pharmacy expenditures of adherent patients (US$4463 vs US$1542 in nonadherent patients); cost savings for avoided hospitalizations for those who were adherent only partially offset the higher pharmacy costs associated with adherence. In conclusion, hospital costs were lower and pharmacy costs were higher in patients who were adherent than in those who were nonadherent |
| UK Psychiatric Morbidity Survey (Knapp et al)29 | Gain information on the nature of the relationship between nonadherence and resource use | Data from a cross-sectional survey of adults living in institutions that had been prescribed antipsychotic medication | Patient self-reported nonadherence to antipsychotic medication; utilization of health care resources during the preceding year; inpatient and external health care costs | N = 658; lower self-reported nonadherence among patients resident in hospital (11.2%) compared with among patients in other types of institutions (21.2%); only medication nonadherence appeared to exhibit a consistent association with greater resource use; patients reporting nonadherence were predicted to have an excess of inpatient costs of £2481 and total service use costs of £5231 per patient per year. In conclusion, medication nonadherence consistently exhibited an association with higher costs; interventions that improve adherence are likely to reduce service use costs |
| Wisconsin Medicaid recipients (Svarstad et al)30 | Assess the relationship between nonadherence, hospitalization, and costs among severely mentally ill patients | Retrospectively collated information from a database of individual data from patients treated with antipsychotics (oral or LAI), lithium, or antidepressants; medical record audits; and a survey of case managers, as well as evidence of prescription medication coverage and acute care hospital admissions from Medicaid | Irregular use of medication (having one or more year quarters during which no claim was made for an oral medication or two or more quarters during which no claim for a LAI medication was made) used as a proxy for nonadherence; hospitalization for psychiatric problems, total number of inpatient days, and actual hospital expenditures | N = 619; 424 with a diagnosis of schizophrenia or schizoaffective disorder, 96% treated with antipsychotics; 31% considered as nonadherent; greater proportion of nonadherent patients (33%) than adherent patients (18%) hospitalized during the study year; greater mean number of hospital days and hospital expenditures in nonadherent patients (13.9 days, US$3421 per year per patient) than in adherent patients (3.6 days, US$1799 per year per patient); nonadherent patients were two times (OR = 1.99) more likely to be hospitalized than adherent patients. In conclusion, nonadherence is a strong predictor of hospital outcomes |
| Impact of patterns of antipsychotic drug use in the Medi-Cal system (McCombs et al)31 | Evaluate whether suboptimal antipsychotic drug use patterns have an impact on direct health care costs | Retrospectively collated information from a claims database of Medicaid (averaged with Medicare data, for patients with dual eligibility) of outpatients with schizophrenia, with a minimum of 2 years of follow-up data available | “Nonadherence” defined as suboptimal use of antipsychotic medication in the form of delays in therapy, changes in therapy, or interrupted therapy; hospital, nursing, or care facility days, and other services provided by mental health providers; average per day cost reported by Medi-Cal or Medicare | N = 2476, 83.5% received antipsychotic medication (98.9% by oral route); association between pattern of active antipsychotic drug therapy (with respect to no therapy) and a significant reduction in total direct costs during a 2-year period of US$10,833 per patient, especially for psychiatric hospital care (US$8027 per patient); association between ; delays and changes in drug therapy were associated with increases of total direct health care costs of US$12,285 and US$17,644 per patient, respectively; continuous treatment did not have a significant effect over total direct costs of care. In conclusion, active drug therapy and continuous treatment were associated with a significant reduction in psychiatric hospital costs; continuous therapy was also associated with higher nursing home costs, possibly because of continuous monitoring of adherence, which offset the hospital cost savings |
Abbreviations: FGA, first-generation antipsychotics; LAI, long-acting injectable; Medi-Cal, California Medicaid; MPR, medication possession ratio; OR, odds ratio; SGA, second-generation antipsychotics.