RESUMEN
IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.
Asunto(s)
Antidepresivos/administración & dosificación , Antipsicóticos/uso terapéutico , Aripiprazol/uso terapéutico , Bupropión/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Sustitución de Medicamentos , Adulto , Antidepresivos/uso terapéutico , Resistencia a Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estados Unidos , VeteranosRESUMEN
UNLABELLED: We examined the impact of two financing strategies--increasing Medicaid dental reimbursements and providing school sealant programs--on dental sealant? prevalence (number of children with at least one sealant) among 7- to 9-year-olds in Alabama and Mississippi counties from 1999 to 2003. METHODS: We used Medicaid claims data in a linear regression model. We regressed number of children sealed per county onto eligible children, median family income, dentist-to-population ratio, and indicator variables for reimbursement increase, presence of community health center (CHC) or school sealant program, and interaction between reimbursement increase and presence of school program or CHC. We also calculated the average incremental cost per sealant from increasing the Medicaid reimbursement rate and then disaggregated it into cost to provide additional sealants and cost to provide the same number of sealants under the higher rate. RESULTS: Increasing the sealant reimbursement rate was associated with a 102 percent increase and a 39 percent increase in sealant prevalence in Mississippi and Alabama, respectively. Introducing school sealant programs more than doubled sealant prevalence in both states. In Mississippi, 85 percent of the average incremental cost from implementing the higher reimbursement rate was due to providing new sealants and 15 percent was due to paying a higher rate for sealants that likely would have been delivered at the old rate. CONCLUSION: Depending on supply and demand conditions in dental markets, both strategies can be effective in increasing sealant prevalence.