Background:Essential tremor (ET) affects nearly 7 million people in the United States and consists of upper limb tremor that can affect activities of daily living, including activities related to work. Research examining the effect of ET on work productivity is limited and there are no studies using validated work productivity instruments. Methods:Clinic-based data were collected between March 2021 and August 2021 from US physicians participating in the Adelphi ET Disease Specific Programme (DSP). Patients were evaluated with the Essential Tremor Rating Assessment Scale (TETRAS), Quality of Life in Essential Tremor (QUEST) questionnaire, and the Work Productivity and Activity Impairment (WPAI) questionnaire. Statistical associations between tremor severity and work productivity were examined. Results:A total of 1,003 ET patients were identified, and 420 patients completed the WPAI questionnaire and were included in this study. Activity impairment was independently associated with tremor severity, adjusting for age, full-time vs. part-time employment, household income, depression, and anxiety. Of those who were employed (n = 165), 133 (80.6%) were employed full-time, and 141 (85.5%) had some level of work impairment. Work impairment was also independently associated with tremor severity, adjusting for the same covariates. Among those patients for whom QUEST responses were available, 47% (64/135) of patients with ET working full-time and 88% (36/41) of those working part-time reported that tremor interfered with work. Discussion:Work impairment is significantly correlated with tremor severity. Although a minority of patients in this clinic-based cohort were identified as employed, nearly all reported a negative impact on work performance.

Background:Essential tremor (ET) is a common movement disorder that affects the upper limbs in vital activities of daily living. Few studies have examined the impact of tremor severity on caregiving intensity. Methods:Clinic-based data were collected in the United States (US) from March 2021 to August 2021 through the Adelphi ET Disease Specific Programme (DSP). Linked data between physician and care partner/patient pairs were used to evaluate care partner-reported weekly hours of patient care. Tremor severity was assessed with the Essential Tremor Rating Assessment Scale (TETRAS) Performance and Activities of Daily Living subscales. Pearson chi-square, correlation and multivariate regression analyses were conducted to examine the relationships between tremor severity and hours of care partner assistance. Results:A quarter of 960 individuals with ET required care partners. Most care partners were spouses (61%), but other family members or friends also served as care partners. About 23% of care partners reported giving constant care, defined as 112 hours per week or more, while the remainder of care partners reported caregiving time averaging 24.5 hours per week. The probability of needing a care partner was significantly associated with tremor severity, and the association between care partner need and tremor severity was moderate (bivariate r = 0.32-0.37) and not substantially impacted by the inclusion of additional covariates (age, sex, race, comorbidity, relationship with patient, and living with patient). Discussion:Roughly 25% of patients with ET have care partner needs, and the number of care partner hours provided is correlated with tremor severity. Therefore, treatments that ameliorate tremor severity have the potential to reduce caregiving intensity in ET.

OBJECTIVE:To conduct a literature review using real-world evidence on the most common pharmacotherapies used in treating essential tremor (ET). BACKGROUND:ET is among the most common movement disorders in the US. Current treatments include pharmacological treatments and surgical interventions, though many patients continue to lack adequate tremor control. Syntheses of published real-world evidence on ET pharmacotherapies are lacking. DESIGN/METHODS:We conducted a comprehensive literature review of English-language studies published between 1966-2022 using PubMed. The review targeted non-clinical trial studies of adults with ET evaluating propranolol, primidone, gabapentin, and/or topiramate, and reporting at least upper limb tremor efficacy, safety/adverse events, tolerability, and/or treatment patterns. Studies reporting ≤10 subjects were excluded. RESULTS:We identified 236 studies. Following title and abstract screening, 75 full-text studies were assessed, with 15 included in data extraction. Patient- or clinician-validated scales were used in 2/15 studies. Activities of daily living and quality of life outcomes were not commonly reported. Up to 81% and 55% of patients used propranolol and primidone, respectively. Gabapentin (30%) and topiramate (20%) were used less frequently. Though clinical response definitions varied, propranolol demonstrated response in 37-56% of patients, and primidone in 43-55% of patients among studies with ≥50 evaluable patients. Approximately one-quarter of patients reported responding to gabapentin or topiramate. Discontinuation rates varied widely across studies, from 10-70% for both propranolol and primidone. Gabapentin and topiramate had discontinuation rates from 26-86% and 26-58%, respectively. Usage, efficacy, and discontinuation were not characterized by line of therapy (i.e. initial vs subsequent treatments) in the assessed studies. CONCLUSIONS:Currently available ET pharmacotherapies may not provide adequate efficacy for many patients, highlighting substantial unmet need. We identified several gaps in the published evidence base, including evaluation of commonly-used ET medications by line of therapy and reporting on validated measures to enable comparisons to new ET pharmacotherapies. Disclosure: Ms. Gerbasi has received personal compensation for serving as an employee of Sage Therapeutics, Inc.. Ms. Gerbasi has stock in Sage Therapeutics. Ms. Gerbasi has received intellectual property interests from a discovery or technology relating to health care. Ms. Tu has received personal compensation for serving as an employee of Medicus Economics, LLC. Mrs. Chertavian has nothing to disclose. Miss Nejati has received stock or an ownership interest from Biogen. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda Therapeutics. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal Pharmaceuticals. Dr. LeWitt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for US WorldMeds LLC. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyowa Kirin Inc. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe-NeuroDerm Neuropharma. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bukwang Pharmaceuticals. Dr. LeWitt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. LeWitt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. LeWitt has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for CLINICAL NEUROPHARMACOLOGY.

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. Results: The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = –0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = –0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. Discussion: This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. Highlights This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.

AIMS:Estimate relative efficacy of zuranolone, a novel oral, Food and Drug Administration-approved treatment for postpartum depression (PPD) in adults vs. selective serotonin reuptake inhibitors (SSRIs) and combination therapies used for PPD in the United States.MATERIALS AND METHODS:Randomized controlled trials (RCTs) for zuranolone and SSRIs, identified from systematic review, were used to construct evidence networks, linking via common comparator arms. Due to heterogeneity in placebo responses, matching-adjusted indirect comparison (MAIC) was applied, statistically weighting the zuranolone treatment arm of Phase 3 SKYLARK Study (NCT04442503) to the placebo arm of RCTs investigating SSRIs for PPD. MAIC outputs were applied in Bucher indirect treatment comparisons (ITCs) and network meta-analysis (NMA), using Edinburgh Postnatal Depression Scale (EPDS) and 17-item Hamilton Rating Scale for Depression (HAMD-17) change from baseline (CFB) on Days 3, 15, 28 (Month 1), 45, and last observation (Day 45, Week 12/18).RESULTS:Larger EPDS CFB was observed among zuranolone-treated vs. SSRI-treated patients from Day 15 onward. Zuranolone-treated (vs. SSRI-treated) patients exhibited 4.22-point larger reduction in EPDS by Day 15 (95% confidence interval: -6.16, -2.28) and 7.43-point larger reduction at Day 45 (-9.84, -5.02) with Bucher ITC. NMA showed EPDS reduction for zuranolone was 4.52 (-6.40, -2.65) points larger than SSRIs by Day 15 and 7.16 (-9.47, -4.85) larger at Day 45. Lack of overlap between study populations substantially reduced effective sample size post-matching, making HAMD-17 CFB analysis infeasible.LIMITATIONS:Limited population overlap between SKYLARK Study and RCTs reduced feasibility of undertaking HAMD-17 CFB ITCs and may introduce uncertainty to EPDS CFB ITC results.CONCLUSIONS:Analysis showed zuranolone-treated patients with PPD experienced greater symptom improvement than SSRI-treated patients from Day 15 onward, with largest mean difference at Day 45. Adjusting for differences between placebo arms, zuranolone may be associated with greater PPD symptom improvement (measured by EPDS) vs. SSRIs.

The well-established dissociation between the ventral object and dorsal spatial processing streams within the primate visual system suggests a contrast between object and spatial cognitive styles. We assessed the validity of this distinction using a self-report questionnaire in a sample of 3839 online participants, and laboratory cognitive tests in a subsample of 196. We found that (1) object and spatial processing preferences were virtually uncorrelated (r = –.05); (2) men, science majors, and people with videogame experience preferred spatial visualization, whereas women, humanities majors, and people with visual arts experience preferred object visualization; and (3) spatial visualizers performed better on tests of mental rotation and virtual maze navigation, whereas object visualizers performed better on a difficult test of picture recognition. The associations among the spatial measures were stronger than those among the object measures, which suggests that spatial visualization may be the more unitary cognitive ability and style. Individual differences in cognitive style may have implications for education.

Objective: To characterize the Essential Tremor (ET) patient population, explore how US physicians perceive goals and efficacy of ET pharmacotherapy, and determine medications prescribed by neurologists versus primary care physicians (PCPs). Background: ET is among the most prevalent movement disorders in adults. However, ET treatment goals and medication prescribing patterns in the US are not well characterized. Design/Methods: Forty PCPs and 61 neurologists, including 24 movement disorder specialists (MDS), completed a questionnaire with 7-point Likert items (1=not important/low association, 7=extremely important/strong association) exploring treatment goals and perceived efficacy of medications used in patients with ET under their management. Results: Surveyed physicians reported seeing ≈3,000 patients with ET each month in total. 51% were ≥65 years of age; only 3% were ≤18 years of age. Overall, 57% of patients were reported to have moderate/severe ET (neurologists: 61% vs. PCPs: 53%; P=0.17). The most prescribed medications were propranolol (34%), primidone (27%), topiramate (11%), gabapentin (11%), clonazepam (10%), and atenolol (10%). Compared to neurologists, PCPs prescribed primidone to a lower proportion of patients and atenolol to a higher proportion (P<0.05). Across physicians, treatment goals rated as most important were maintaining quality of life, maintaining function, reducing hand tremor, tolerability, long-term efficacy, patient compliance, and slowing disease progression (mean importance ≥6.0). The importance of long-term efficacy and patient compliance were rated higher by neurologists than PCPs (P<0.01). Both neurologists and PCPs rated medications as having limited-to-moderate effect (mean range: 1.8–4.9) on top-rated attributes, with variation by physician type and medication. Conclusions: Most surveyed physicians prioritized patient function and well-being in the treatment of adults with ET. Although PCPs and neurologists differ partly in treatment patterns, goals, and perception of drug efficacies, the overall consensus is that current medications are inadequate in addressing patient-relevant outcomes, highlighting an unmet need for more effective pharmacotherapy. Disclosure: Ms. Gerbasi has received personal compensation for serving as an employee of Sage Therapeutics, Inc.. Ms. Gerbasi has stock in Sage Therapeutics. Ms. Gerbasi has received intellectual property interests from a discovery or technology relating to health care. Dr. Elble has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Elble has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage . Dr. Elble has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ES Therapeutics. Dr. Elble has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Applied Therapeutics. Dr. Elble has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Praxis. Eddie Jones, BA has nothing to disclose. Mr. Gillespie has nothing to disclose. Mr. Jarvis has nothing to disclose. Mrs. Chertavian has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Bankole has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Bankole has stock in Sage Therapeutics. Dr. Shankar has received personal compensation for serving as an employee of Biogen. Dr. Shankar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Trinity Lifesciences, Triangle Insights Group. Dr. Shankar has stock in Biogen. Dr. Shankar has stock in Multiple Biotech Companies. Dr. Shih has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Encora Therapeutics. Dr. Shih has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Shih has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis Precision Medicines. Dr. Shih has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Shih has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for WCG Medavante. Dr. Shih has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Shih has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley . The institution of Dr. Shih has received research support from Abbott. The institution of Dr. Shih has received research support from Praxis Precision Medicines. Dr. Shih has received personal compensation in the range of $500-$4,999 for serving as a Consultant with German Accelerator.

Background Essential tremor (ET) is among the most common movement disorders in adults. While ET is diagnosed and primarily characterized by the presence of tremor, it also can impact cognition, sleep, mood, and motor functioning more broadly. The manifestations of ET can have various consequences, including difficulty with activities of daily living (ADL), embarrassment, and overall decline in health-related quality of life, which have not been fully explored in prior studies. Objective We performed a systematic literature review to comprehensively characterize the burden experienced by patients with ET from the clinical and humanistic perspectives, focusing on outcomes beyond tremor. Methods This systematic literature review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches in PubMed, Embase, and Cochrane Library identified original, observational studies of the clinical and humanistic burden in adult patients with ET published in English between 2010 and 2020. Studies assessing epidemiology, treatment patterns, or disease management were excluded. Search results were screened according to pre-determined eligibility criteria. Data from included studies were collected, independently verified, and qualitatively synthesized. Results Following the screening of 2,303 records and 145 full-text articles, 39 studies were identified. There was significant heterogeneity in study designs, statistical approaches, and patient cohorts across the included studies. Patients with ET in these studies exhibited more severe disabilities and reduced independence compared to healthy individuals, and they often struggled to perform ADL and relied on caregivers for physical and emotional support. Patients also experienced various issues with movement and balance, increased risk of falls, depression, anxiety, poor sleep quality, and psychosocial consequences including embarrassment, apathy, and enfeeblement. Conclusion A systematic literature review of non-tremor manifestations and/or consequences of ET identified far-reaching negative impacts on patients' ability to function independently and revealed accompanying psychosocial effects, including social fear and embarrassment. The reduced function and psychosocial deficits observed in patients with ET result in significant clinical and humanistic burdens, decreasing quality of life. Future studies should evaluate this condition beyond the tremor itself to provide an improved understanding of the multi-dimensional burden of the disease, thereby highlighting the need to diagnose and appropriately manage patients with ET.

Background:Essential tremor (ET) is one of the most common movement disorders worldwide, yet the size of the pediatric ET population is not well understood. The objective of this review was to identify, evaluate, and synthesize evidence describing the epidemiology of pediatric ET in the United States published between 2010 and 2020.Methods:The authors searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews using terms related to ET, epidemiology, and pediatric patients. Eligibility criteria included observational studies that reported primary data on pediatric prevalence or incidence of ET or age of onset/diagnosis of ET. A total of 562 unique articles were identified for screening.Results:The review did not identify any studies that reported information on pediatric prevalence or incidence of ET, or age of ET diagnosis among nonpediatric patients. A total of 10 samples were identified, all of which described age of ET onset that ranged from 27.0 years to 56.7 years among 9 adult populations (weighted mean of 41.6 years) and 9.7 years in a single pediatric sample. One adult sample reported that 13% of all ET cases reported onset by age 14, and 21.8% of all ET cases reported onset by age 18.Discussion:There is a notable lack of recent data describing the incidence and prevalence of pediatric ET in the United States. Many children who present with symptoms of ET may not be diagnosed until later in life, and an increased awareness of pediatric ET could allow for early identification and monitoring of these patients.

Background: Brexanolone (BRX) injection was approved by the United States Food and Drug Administration in 2019 for the treatment of adults with postpartum depression (PPD) based on two Phase 3 clinical trials. Materials and Methods: Data from the three trials were combined. PPD-specific 17-item Hamilton Rating Scale for Depression (HAMD-17) group-level minimal important difference (MID) and patient-level meaningful change (meaningful change threshold [MCT]) were estimated and applied to differences in BRX versus placebo (PBO) at hour 60 (primary endpoint) and day 30 (end of trial follow-up). Likelihood of HAMD-17 response and remission and Clinical Global Impression of Improvement (CGI-I) response for BRX versus PBO were assessed at hour 60 and as sustained through day 30 using relative risk. Associated number needed to treat (NNT) and number needed to harm (NNH) values were also estimated. Results: Two-hundred nine patients were included. The average HAMD-17 MID estimate was −2.1; the least-squared mean difference between BRX and PBO exceeded this at hour 60 and day 30. Minimal, moderate, and large MCTs were estimated to be −9, −15, and −20 points, respectively. Significantly more BRX-treated than PBO-treated patients achieved minimal, moderate, and large change (all ps < 0.05) at hour 60 and large meaningful response at day 30 (p < 0.05). BRX-treated patients were more likely to sustain HAMD-17 remission and CGI-I response through day 30 versus PBO. NNTs ranged from 4 to 8, with NNH of 97. Conclusions: BRX provided meaningful changes relative to PBO, rapid (hour 60), and sustained improvements (day 30) in PPD symptoms, low NNT, and large NNH. These results may help inform treatment decision-making. Clinicaltrials.gov registration numbers: NCT02614547, NCT02942004, and NCT02942017.

Objective To evaluate the health-related quality of life (HRQoL) burden associated with postpartum depression (PPD), determine the extent to which clinical response impacts HRQoL, and estimate the impact of PPD and clinical response on healthcare resource utilization (HRU) and productivity. Methods Patient data (n = 127) from two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of brexanolone injection in adults with PPD were employed for these posthoc analyses. HRQoL and health utility was assessed with the SF-36-v2 Health Survey (SF-36v2) acute version. The 17-item Hamilton Rating Scale for Depression (HAMD-17) total score was used to identify clinical response (>= 50% reduction in HAMD-17 total score). Baseline HRQoL burden was assessed by comparison to age- and gender-adjusted population normative data from the 2009 QualityMetric PRO Norming study. The impact of clinical response was evaluated by comparing day 7 and day 30 SF-36v2 scores between clinical responders and non-responders. Interpretations of the meaningfulness of clinical response were indirectly estimated via 2017 National Health and Wellness Survey data linking SF-36v2 mental component summary (MCS) scores to (HRU) and productivity. Results Baseline HRQoL of patients with PPD was significantly below normative values. Day 7 and day 30 clinical response were associated with large and statistically significant improvements in HRQoL, greater likelihood of meeting SF-36v2 responder definitions, and reduced impairment. MCS levels corresponding to those observed in clinical responders were linked to lower HRU and productivity loss relative to non-responders. Conclusions PPD places a substantial burden on HRQoL. Achievement of rapid clinical response (at day 7) and clinical response sustained several weeks following the end of treatment (day 30) led to significant improvement in HRQoL, suggesting the importance of identifying women with PPD and providing effective treatment options.

Essential tremor (ET) is a common neurological movement disorder that affects more than 6 million adults in the United States (US). It is often associated with comorbidities and can cause substantial disability. Current treatments have demonstrated limited efficacy which may be linked to poor adherence. This study examined the comorbidity burden and treatment switches and discontinuation in a large, real-world patient population. Adults (≥18 years) with an ICD-10 ET diagnosis were identified from a US claims database (Truven Health (IBM) MarketScan®; 2015-2018) and assessed for at least 12 months post diagnosis. Pre-identified ET treatments were used to evaluate those on therapy. Index treatment was defined as the first observed treatment after ET diagnosis. Patients with differential diagnoses for other movement disorders, except Parkinson’s disease, were excluded. A limitation of the algorithm is that patients identified may have been previously diagnosed with ET and/or received ET treatments. The algorithm identified 26,278 patients (mean age: 61 years) who were also receiving treatment for ET. The most common comorbidities observed at or 6 months before index treatment were essential hypertension (52%), other nervous system disorders (45%), lipid metabolism disorders (44%), and mood and anxiety disorders (37%). Among patients receiving ET medications for their index treatment (n=25,872), propranolol (29%) and primidone (18%) were the most frequently observed treatments. Only 14% of patients persisted with their initial medication, while the majority switched (45%) or discontinued (41%) them. More than 50% of patients received at least two medication regimens in the 12 months after index treatment. A small proportion of patients (3%) received surgical interventions, typically after multiple medication regimens. ET patients experience a high comorbidity burden. In addition, high rates of switching and discontinuation of ET medications suggest an unmet need for improved treatment options.

The objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms. Associations were assessed at day 30 (end-of-trial follow-up). Pearson correlation assessed the relationship between EPDS and PHQ-9 item and total scores and HAMD-17 total score. Cohen’s kappa assessed agreement of EPDS remission (score < 10) and PHQ-9 remission (score < 5) with HAMD-17 remission (score ≤ 7). Ordinary least squares (OLS) regression models were used to develop equations estimating HAMD-17 total scores from EPDS and PHQ-9 scores, respectively. The total scores showed large correlations (HAMD-17/EPDS: r = 0.71, p < 0.001; HAMD-17/PHQ-9: r = 0.75, p < 0.001). Individual EPDS and PHQ-9 items significantly correlated (r= 0.35 to 0.67, all p < 0.001) with HAMD-17 total score. EPDS had 79% sensitivity and 67% specificity to detect HAMD-17 remission; corresponding estimates for PHQ-9 were 76% and 78%. OLS models yielded the following equations: HAMD-17 total = 2.66 + (EPDS total × 0.87) and HAMD-17 total = 3.99 + (PHQ-9 total × 0.97). There were large and statistically significant associations between patient-reported outcomes (EPDS, PHQ-9) and clinician-reported outcomes (HAMD-17) as clinical improvements were associated with patient-reported symptom improvement. These results provide tools to help translate clinical trial data to clinical practice, thus aiding shared decision-making for this critical population.

BACKGROUND:Brexanolone injection (BRX) was approved by the FDA in 2019 for the treatment of adult patients with postpartum depression (PPD), but its cost-effectiveness has not yet been evaluated.OBJECTIVE:To estimate the cost-effectiveness of BRX compared with treatment with selective serotonin reuptake inhibitors (SSRIs) for PPD.METHODS:We projected costs (2018 U.S. dollars) and health (quality-adjusted life-years [QALYs]) for mothers treated with BRX or SSRIs and their children. A health state transition model projected clinical and economic outcomes for mothers based on the Edinburgh Postnatal Depression Scale, from a U.S. payer perspective. The modeled population consisted of adult patients with moderate to severe PPD, similar to BRX clinical trial patients. Short-term efficacy for BRX and SSRIs came from an indirect treatment comparison. Long-term efficacy outcomes over 4 weeks, 11 years (base case), and 18 years were based on results from an 18-year longitudinal study. Maternal health utility values came from analysis of trial-based short-form 6D responses. Other inputs were derived from the literature.RESULTS:The incremental cost-effectiveness ratio for BRX versus SSRIs was $106,662 per QALY gained over an 11-year time horizon. Drug and administration costs for BRX averaged $38,501, compared with $25 for SSRIs over the studied time horizon. Maternal total direct medical costs averaged $65,908 in the BRX arm, compared with $73,653 in the SSRI arm. BRX-treated women averaged 6.230 QALYs compared with 5.979 QALYs for the SSRI arm. Adding partner costs and utilities in a sensitivity analysis further favored BRX. Results were sensitive to the severity of PPD at baseline and the model time horizon. Probabilistic sensitivity analyses indicated that BRX was cost-effective at the $150,000-per-QALY threshold with 58% probability.CONCLUSIONS:Analysis using a state transition model showed BRX to be a cost-effective therapy compared with SSRIs for treating women with PPD.DISCLOSURES:This study was funded by Sage Therapeutics, Cambridge, MA. Eldar-Lissai, Gerbasi, and Hodgkins are employees of Sage Therapeutics and own stock or stock options in the company. Gerbasi also reports previous employment with Policy Analysis Inc. Cohen contributed to this work as an independent consultant. Meltzer-Brody has a sponsored clinical research agreement with Sage Therapeutics to the University of North Carolina, as well as a sponsored research agreement from Janssen to the University of North Carolina, unrelated to this work. Meltzer-Brody has also received personal consulting fees from Cala Health and MedScape, unrelated to this work. Johnson, Chertavian, and Bond are employees of Medicus Economics, which was paid fees by Sage to conduct the research for this study. Study findings do not necessarily represent the views of CEVR or Tufts Medical Center.

Background The Zanmi Lasante Depression Symptom Inventory (ZLDSI) is a screening tool for major depression used in 12 primary care clinics in Haiti’s Central Plateau. Although previously validated in a clinic-based sample, the present study is the first to evaluate the validity and clinical utility of the ZLDSI for depression screening in a school-based population in central Haiti. Methods We assessed depressive symptoms in a school-based sample of transitional age youth (18–22 years; n = 120) with the ZLDSI. Other mental health-related assessments included a modified Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) for current Major Depressive Episode, the Center for Epidemiologic Studies Depression Scale, and selected items adapted from the Global School-Based Health Survey mental health module. Diagnostic assignments of major depressive episode (MDE) were based on modified SCID interviews. Results The ZLDSI demonstrated good overall accuracy in identifying current MDE (Area under the Curve = .92, 95% CI = .86, .98, p < .001). We ascertained ≥12 as the optimal cut-off point to screen for depression with a sensitivity of 100% and a specificity of 73.9%. In addition, the ZLDSI was associated with other measures of depressive symptoms, suggesting that it demonstrates construct validity. Conclusions Study findings support that the ZLDSI has clinical utility for screening for depression among school-going transitional age youth.