Sam Leo

To assess the physical, psychological, social, and professional impact of tardive dyskinesia (TD) on patients in the United States. An online survey (April 2020-June 2021) to assess patient burden of TD was developed using targeted literature review and interviews with clinicians, patients, and caregivers. Survey participants (aged ≥ 18 years) with current diagnoses of TD and schizophrenia, bipolar disorder, or major depressive disorder rated the 7-day impact of TD on their physical, psychological, and social functioning via Likert scales (scored from 1 [least impact] to 5 [most impact]). Impact scores were calculated and summarized descriptively overall by self-reported disease severity and underlying disease. Participants also completed the Work Productivity and Activity Impairment Questionnaire and reported the impact of TD on their underlying psychiatric condition. Overall, 269 patients (mean [SD] age = 40.6 years [9.9]; 74.7% employed) responded to the survey. Mean (SD) impact scores of 3.1 (0.9), 3.5 (1.0), and 3.2 (1.1) were reported in the physical, psychological, and social domains, respectively, and scores increased with reported TD symptom severity. Patients with underlying schizophrenia reported the highest burden for all domains. Patients reported 66.2% activity impairment because of TD. Employed patients (n = 193) indicated 29.1% absenteeism, 68.4% presenteeism, and 73.5% overall work impairment. Over one-third of patients reported skipping/reducing (48.4%) or stopping (39.3%) their antipsychotic medication and stopping visits to clinicians treating their underlying condition (35.7%) because of TD. TD imposes a substantial burden on patients' physical, psychological, social, and professional lives and impacts management of their underlying condition.

INTRODUCTION: Chorea, a common clinical manifestation of Huntington's disease (HD), involves sudden, involuntary movements that interfere with daily functioning and contribute to the morbidity of HD. Tetrabenazine and deutetrabenazine are FDA-approved to treat chorea associated with HD. Compared to tetrabenazine, deutetrabenazine has a unique pharmacokinetic profile leading to more consistent systemic exposure, less frequent dosing, and a potentially more favorable safety/tolerability profile. Real-world adherence data for these medications are limited. Here, we evaluate real-world adherence patterns with the vesicular monoamine transporter 2 inhibitors, tetrabenazine and deutetrabenazine, among patients diagnosed with HD. METHODS: Insurance claims data from the Symphony Health Solutions Integrated Dataverse (05/2017-05/2019) were retrospectively analyzed for patients diagnosed with HD (ICD-10-CM code G10). Patients were categorized into cohorts based on treatment. Outcomes included adherence, which was measured by proportion of days covered (PDC), adherence rate (PDC > 80%), and discontinuation rates during the 6-month follow-up period (after a 30-day dose stabilization period). RESULTS: Patient demographic characteristics between the deutetrabenazine (N = 281) and tetrabenazine (N = 101) cohorts were comparable at baseline. Mean ± SD PDC was significantly higher in the deutetrabenazine versus tetrabenazine cohort (78.5% ± 26.7% vs. 69.3% ± 31.4%; P < 0.01). Similarly, a higher adherence rate was observed in the deutetrabenazine versus tetrabenazine cohort, though the difference was not statistically significant (64.1% vs. 55.4%; P = 0.1518). Discontinuation rates were significantly lower in the deutetrabenazine versus tetrabenazine cohort during the 6-month follow-up period (1 month, 3.5% vs. 9.2%; 3 months, 14.7% vs. 23.3%; 6 months, 25.4% vs. 37.2%; P < 0.05). CONCLUSIONS: Results from this real-world analysis indicate that patients treated with deutetrabenazine are more adherent to treatment and have lower discontinuation rates compared with patients in the tetrabenazine cohort. However, a potential limitation is overestimated adherence, as claims for prescription fills may not capture actual use. Additional research is warranted to explore the differences in adherence patterns between treatments, which may inform treatment decision-making.

BACKGROUND: Antipsychotic medications are used to treat schizophrenia and may be associated with adverse effects, including tardive dyskinesia (TD), following prolonged use or upon changes in dosing regimen. OBJECTIVE: This retrospective analysis evaluated the burden of antipsychotic dose reduction in Medicare patients with schizophrenia. METHODS: This matched cohort study used Medicare claims data (2006-2017) analyzed for patients with schizophrenia and two or more claims for antipsychotics, with one or more antipsychotic monotherapy period ≥ 90 days. Cohorts were defined for patients with antipsychotic dose reductions ≥ 10% and stable doses. A separate analysis was conducted using patients with dose reductions ≥ 30%. Outcomes included all-cause emergency room (ER) visits, all-cause inpatient visits, schizophrenia relapse, other psychiatric relapse, and TD diagnosis. Covariates included age, disease duration, comorbidities, and medication use. RESULTS: The analysis included 276,030 patients with ≥ 10% dose reductions and 211,575 patients with ≥ 30% dose reductions. Patient characteristics were balanced between cohorts. Patients with ≥ 10% or ≥ 30% dose reductions had a shorter time to ER visit, inpatient visit, schizophrenia relapse, other psychiatric relapse, and TD diagnosis versus those receiving stable doses (all p < 0.001). Significance was maintained when unmatched baseline characteristics were adjusted. CONCLUSIONS: Patients with antipsychotic dose reductions may be at risk for increased ER visits, increased hospitalizations, and significant unfavorable mental health-related clinical outcomes, suggesting that dose reduction may increase overall health care burden in some patients with schizophrenia. This work highlights the need for alternative strategies in the management of patients with TD.

INTRODUCTION: Chorea is characterized by sudden, involuntary movements that interfere with quality of life (QOL). Utility values measure preferences for different health states and reflect societal perceived disease severity. To date, no studies have reported utility values specifically for Huntington's disease (HD) chorea. We estimated impact on QOL of HD chorea severity using utility values from the general population. METHODS: Participants were enrolled using computer-assisted telephone interviews. Participants read vignettes describing four health states for varying levels of chorea severity, with the same underlying HD severity. Time trade-off (TTO) methods were used to estimate utility values, which range from -1 (worse than death) to +1 (perfect health) and represent the number of years in an imperfect health state an individual is willing to give up to live in full health. TTO utilities were augmented with visual analog scale (VAS) participant responses. The primary outcome was HD chorea utility estimated by TTO. RESULTS: Mean ± SD TTO-derived utility values were 0.07 ± 0.52, 0.26 ± 0.50, 0.48 ± 0.47, and 0.64 ± 0.41 for severe, moderate/severe, moderate/mild, and mild chorea severity, respectively. Differences between each health state and its adjacent less severe health state were statistically significant (all P < 0.0001). Respondents were willing to give up 3.6, 5.2, 7.4, and 9.3 years during a 10-year life span to avoid living with mild, mild/moderate, moderate/severe, and severe chorea, respectively. VAS and TTO results were consistent. CONCLUSIONS: Significant decreases in utility values were seen as HD chorea severity increased. These data can be leveraged for cost-effectiveness modeling to better understand the value of treatments for chorea.

BACKGROUND: Tardive dyskinesia (TD) has a multidimensional impact on patients with TD and, as importantly, their caregivers. An online survey was developed and administered to assess patient and caregiver burden of TD. Survey participants were unpaid caregivers for patients with diagnoses of TD and schizophrenia, bipolar disorder, and/or major depressive disorder. Overall, 162 caregivers rated the 7-day impact of TD on the physical, psychological, and social functioning of patients and the impact of TD on these domains in their own lives and in their professional lives. RESULTS: Across physical, psychological, and social domains, most caregivers (82.7%) reported that TD had severe impact on the cared-for patients, and 23.5% reported severe impact of TD in their own lives. Caregivers experienced 46.4% activity impairment, and caregivers who were employed (n = 136) experienced 49.5% overall work impairment because of TD-related caregiving. CONCLUSIONS: These results suggest that TD imposes substantial burden for both caregivers and patients.