Epidemiology of Treatment-Resistant Depression in the United States.

Background: The prevalence of treatment-resistant depression (TRD) among patients with pharmaceutically treated depression (PTD) varies greatly in publications. The aim of this study is to estimate the prevalence of TRD using 2 large claims databases in the US.Methods: This cross-sectional study used data from the Humana and Optum databases. Patients aged ≥ 18 years who had at least 1 diagnosis of major depressive disorder (ICD-10-CM codes: F32.xx, F33.xx) and 1 antidepressant prescription filled in 2018 were identified as having PTD. Among patients with PTD, TRD was defined as experiencing failure of treatment with at least 2 antidepressants with ≥ 4 weeks of adequate treatment. We estimated the age- and gender-standardized prevalence of TRD and then used logistic regression to investigate if TRD risk varies by age, sex, race, and geographic region. Finally, we described the timeline of TRD development in incident PTD patients.Results: We identified 296,055 and 277,941 patients with PTD in the Humana and Optum databases, among whom 17,640 (6.0%) and 16,131 (5.8%) had TRD. After age and sex standardization, TRD prevalence among PTD patients was 6.8% in Humana vs 5.8% in Optum. Females, middle-aged adults, and White patients had higher risk of TRD. The median time from index antidepressant use to TRD was about 6 months in incident PTD patients.Conclusions: The prevalence of TRD among patients with PTD was similar in the 2 databases. TRD prevalence varies by sex, race, and age, with a higher prevalence in females, White patients, and those in the age group of 45-64 years. However, the absolute differences were small.

An observer-blinded study of 1% permethrin creme rinse with and without adjunctive combing in patients with head lice.

OBJECTIVES: To determine if NIX (Warner Lambert Healthcare, Morris Plains, NJ) 1% Permethrin Creme Rinse Lice Treatment (1% PLT) without combing will effectively treat >/=95% of patients on day 2 or on day 15; to determine whether combing influences efficacy. STUDY DESIGN: A randomized, observer-blinded study enrolled 95 infested adults and children. All patients were treated with 1% PLT on day 1 and, if still infested, on day 8. One third of households were randomized to the combing group and two thirds to the no-combing group. Efficacy was assessed by: (1) visual inspection on days 1, 2, 8, 9, and 15 and, (2) shampooing/straining on days 2, 9, and 15. The target efficacy was 95%. RESULTS: In the no-combing group, the lice-free rate was 83.1% on day 2 (95% CI, 71.0-91.6), 45.8% on day 8 (before second treatment) (95% CI, 32.7-59.2), 77.6% on day 9 (95% CI, 64.7-87.5), and 78.3% on day 15 (95% CI, 65.8-87.9). Adjunctive combing did not improve efficacy on any day. CONCLUSIONS: In this population, 1% PLT was significantly less than 95% effective and suggests resistance to 1% PLT. The failure of nit removal combing by nonprofessional caregivers to improve efficacy demonstrates the unreliability of combing as adjunctive treatment in this setting.

Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects.

Safety and pharmacokinetics (PK) of the antiparasitic drug ivermectin, administered in higher and/or more frequent doses than currently approved for human use, were evaluated in a double-blind, placebo-controlled, dose escalation study. Subjects (n = 68) were assigned to one of four panels (3:1, ivermectin/placebo): 30 or 60 mg (three times a week) or 90 or 120 mg (single dose). The 30 mg panel (range: 34 7-594 microg/kg) also received a single dose with food after a 1-week washout. Safety assessments addressed both known ivermectin CNS effects and general toxicity. The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose of 200 microg/kg. All dose regimens had a mydriatic effect similar to placebo. Adverse experiences were similar between ivermectin and placebo and did not increase with dose. Following single doses of 30 to 120 mg, AUC and Cmax were generally dose proportional, with t(max) approximately 4 hours and t1/2 approximately 18 hours. The geometric mean AUC of 30 mg ivermectin was 2.6 times higher when administered with food. Geometric mean AUC ratios (day 7/day 1) were 1.24 and 1.40 for the 30 and 60 mg doses, respectively, indicating that the accumulation of ivermectin given every fourth day is minimal. This study demonstrated that ivermectin is generally well tolerated at these higher doses and more frequent regimens.