Exploring real-world symptom impact and improvement in well-being domains for tardive dyskinesia in VMAT2 inhibitor-treated patients via clinician survey and chart review.

Introduction: Two vesicular monoamine transporter 2 (VMAT2) inhibitors are approved in the United States (US) for the treatment of tardive dyskinesia (TD). There is a paucity of information on the impact of VMAT2 inhibitor treatment on patient social and physical well-being. The study objective was to elucidate clinician-reported improvement in symptoms and any noticeable changes in social or physical well-being in patients receiving VMAT2 inhibitors. Methods: A web-based survey was offered to physicians, nurse practitioners, and physician assistants based in the US who prescribed valbenazine for TD within the past 24 months. Clinicians reported data from the charts of patients who met the inclusion criteria and were allowed to recall missing information. Results: Respondents included 163 clinicians who reviewed charts of 601 VMAT2-treated patients with TD: 47% had TD symptoms in ≥2 body regions, with the most common being in the head or face and upper extremities. Prior to treatment, 93% of patients showed impairment in ≥1 social domain, and 88% were impaired in ≥1 physical domain. Following treatment, among those with improvement in TD symptoms (n = 540), 80% to 95% showed improvement in social domains, 90% to 95% showed improvement in physical domains, and 73% showed improvement in their primary psychiatric condition. Discussion: In VMAT2-treated patients with TD symptom improvement, clinicians reported concomitant improvement in psychiatric disorder symptoms and in social and physical well-being. Regular assessment of TD impact on these types of domains should occur simultaneously with movement disorder ratings when evaluating the value of VMAT2 inhibitor therapy.

Clinician Perceptions of the Negative Impact of Telehealth Services in the Management of Drug-Induced Movement Disorders and Opportunities for Quality Improvement: A 2021 Internet-Based Survey.

Purpose: Tardive dyskinesia (TD) is a drug-induced movement disorder (DIMD) seen in patients taking dopamine-receptor blocking agents (DRBAs). Clinicians should regularly monitor patients with or at risk of developing DIMDs; however, telehealth visits during the COVID-19 pandemic presented several significant challenges related to screening and care of these patients. In this observational survey study, respondents compared in-person with video/telephone visits to determine the impact on the evaluation, diagnosis, and monitoring of patients with DIMDs. Methods: The online survey was conducted (May 14-June 21, 2021) with qualified clinicians who prescribed a vesicular monoamine transporter 2 inhibitor or benztropine for DIMDs in the past 6 months, spent ≤70% of their professional time in the clinic, and conducted telehealth visits with ≥15% of their patients between December 2020 and January 2021. The questionnaire probed clinicians about their ability to evaluate, diagnose and monitor (hereinafter referred to as manage) patients with DIMDs via telehealth. Results: Survey respondents included 277 clinicians from psychiatry (n = 168) and neurology (n = 109) practices. Certain signs and symptoms (visual cues) used for diagnosis of DIMDs were not observable through telehealth and evaluation was comparatively more difficult with phone visits than video visits. Patients without caregivers and lower-functioning patients were at higher risk of missed diagnosis of DIMDs and were also difficult to monitor via telehealth. Limited access to computers or telephones and patients living alone were among the top socioeconomic barriers limiting clinicians' ability to diagnose DIMDs. Patients without a regular caregiver were also more difficult for clinicians to evaluate and monitor adequately. Further, most clinicians received no training related to evaluation of DIMDs via telehealth or engaging caregivers as health care partners. Conclusion: Our study highlights specific limitations and challenges and provides considerations to help clinicians better manage DIMDs in the context of telehealth services.

Economic burden and antidepressant treatment patterns among patients with major depressive disorder in the United States.

BACKGROUND: The prevalence of major depressive disorder (MDD) continues to rise year over year, resulting in significant economic implications. However, when patients are treated with contemporary standard-of-care antidepressant pharmacotherapies, a suboptimal response is often attained, resulting in frequent treatment changes. OBJECTIVE: To compare health care resource utilization (HCRU) and all-cause medical and pharmacy costs between commercially insured patients with an MDD diagnosis and matched non-MDD patients and explore treatment patterns among patients with MDD initiating antidepressant pharmacotherapy. METHODS: This was a retrospective, observational analysis of IBM MarketScan US commercial claims data. Adults aged 18 years and older with continuous enrollment 12 or more months before and after the patient's first MDD diagnosis from 2017 to 2018 were included in the analysis. HCRU and all-cause medical and pharmacy costs were compared among patients with MDD and a 1:1 exact-matched cohort of non-MDD patients during the same period (Objective 1). Treatment patterns (persistence, discontinuation, switch, combination, and augmentation) were analyzed for patients with MDD starting first-line antidepressant monotherapy for up to 12 months following their antidepressant initiation index date (Objective 2). Time to first treatment change or discontinuation was calculated and treatment patterns were graphically displayed in Sankey diagrams. RESULTS: 625,272 patients with MDD were matched 1:1 to a cohort of non-MDD patients in Objective 1. Patients with MDD had statistically significantly greater all-cause medical (20.4 vs 9.4; P < 0.0001), outpatient (19.5 vs 9.0; P < 0.0001), emergency department (0.51 vs 0.23; P < 0.0001), inpatient (0.35 vs 0.11; P < 0.0001), and any mental health-related (7.7 vs 0.58; P < 0.0001) visits compared with non-MDD patients. Mean all-cause medical costs were $6,809 (P < 0.0001) higher among patients with MDD than among patients without MDD ($13,183 vs $6,374, respectively). In Objective 2, 44,485 patients with MDD who received antidepressant monotherapy as their first-line MDD treatment were examined. Among the first treatment patterns observed following initiation, 19.3% of patients persisted with their first-line therapy, 56.2% discontinued antidepressant therapy, 24.5% experienced a treatment change (switching, adding a second antidepressant, or augmenting their existing therapy). The median days until first treatment change were 65 days for those discontinuing and 47 days for those switching antidepressants. Among the 24.5% of patients with a treatment change, 50.0% experienced another change in therapy within 30 days. CONCLUSIONS: The HCRU and costs accrued for patients with MDD is significantly greater than those for non-MDD patients. A large proportion of patients with MDD experienced treatment changes shortly after initiating their first-line antidepressant therapy. The results of this study highlight the need for reevaluation of the current MDD treatment paradigm. DISCLOSURES: Drs Zhu and Namjoshi are employees of Biogen Inc. and may hold stock. Dr Ferries and Ms Suthoff are employees of Sage Therapeutics, Inc., and may hold stock and/or stock options. Dr Bera has no potential conflicts of interest to disclose. This research was funded by Sage Therapeutics and Biogen. Manuscript editorial services were provided by Boston Strategic Partners, Inc., funded by Sage Therapeutics and Biogen. This work was supported by Sage Therapeutics, Inc., and Biogen. The authors had full editorial control of the manuscript and provided final approval on all content.

Suicide hotspots, interventions, and future areas of work at a Californian university.

We identified suicide hotspots and effective interventions at a Californian university. We collected timeline and location data of suicides and interventions occurring 2000-2016. We interviewed administrative staff concerning mental health support and suicide prevention systems. We identified three hotspots. Suicides occurred most often on Thursday, in January, during hours of darkness, in a particular plaza and parking structure. Following interventions, suicides declined dramatically. Many interventions followed international guidelines. Low-cost solutions (e.g. ground deterrents) may have contributed to the suicide decrease. To monitor intervention effectiveness, we suggest a GIS-mediated approach.

A Pilot Study of Cultural/Racial Differences in Patient Perspectives on Long-Acting Injectable Antipsychotics for the Treatment of Schizophrenia.

OBJECTIVE: Long-acting injectable (LAI) antipsychotics improve treatment outcomes in patients with schizophrenia but are often reserved for only the most severely affected or nonadherent. Studies show cultural/racial differences in prescribing. This pilot study examined prescriber-patient interactions and cultural/racial differences in perceptions of LAIs among patients. METHODS: A linguist analyzed 120 prescriber-patient conversations representing selected patient cultural/racial subgroups (European American, African American, Latino American; n=40 each) to identify similarities and differences in conceptualization and attitudes toward LAIs. RESULTS: Of 35 LAI-naive patients offered LAIs, 9% (3/35) responded favorably, 46% (16/35) were neutral/passive, and 46% (16/35) had concerns or viewed LAIs as unfavorable. Among LAI-naive patients, favorable or neutral/passive responses were reported for 50% (7/14) of European Americans, 63% (10/16) of African Americans, and 40% (2/5) of Latino Americans. The majority of LAI-naive patients (57% [20/35]) accepted LAI prescriptions, including 53% (17/32) of those who initially were neutral/passive or refused treatment (European American, 42% [5/12]; African American, 53% [8/15]; Latino American, 80% [4/5]). Fifty-seven percent (68/120) of patients expressed treatment goals. Goals of positive/negative symptom control were associated with positive attitudes toward LAIs while patients with goals focused on control of anxiety and insomnia tended to have negative attitudes toward LAIs. Latino-American patients who expressed treatment goals seemed more focused on discomfort control (67% [12/18]); goals of European Americans and African Americans were more equally distributed. CONCLUSIONS: Equal numbers of LAI-naive patients had unfavorable/concerned or neutral/passive attitudes toward treatment; relatively few patients responded favorably. The limited sample size precludes cultural/racial-specific conclusions.

Patient outcomes within schizophrenia treatment: a look at the role of long-acting injectable antipsychotics.

Compliance is a critical issue across all chronic conditions, including schizophrenia. Compliance is not an all-or-nothing phenomenon, with a continuum from taking all medications as prescribed to partial compliance to complete noncompliance. Partial compliance is a serious problem that may result in abrupt dose changes leading to unanticipated adverse effects and can demoralize the patient. Further, there is a nearly 5-fold increase in the risk of relapse in first-episode patients when antipsychotic drug treatment is discontinued. Taken together, these data indicate that it is critical to ensure continuous delivery of antipsychotic treatment. Atypical antipsychotic medications were expected to result in better adherence, primarily because of the anticipated improved efficacy and safety profile. However, atypical agents have poor adherence, irrespective of the type of atypical medication, making it difficult to predict which patients are taking their oral medications. Long-acting injectable (LAI) agents may minimize the fluctuations in peak and overall plasma levels compared with oral agents, indicating they may allow more consistent and predictable administration. Based on clinical experience in my practice, several important observations regarding LAI use in patients with schizophrenia have been identified. First, there are potential advantages to using LAIs, including assistance in understanding reasons for poor response, the possibility of eliminating daily pill ingestion, and the elimination of the abrupt loss of medication coverage. There are also several potential obstacles to the use of LAIs, including a lack of infrastructure for the delivery and disposal of syringes and the ease of use with the oral agents. Several strategies can be used to increase patient willingness to initiate and continue LAI therapy. Strategies to improve acceptance involve presenting the option with enthusiasm, ensuring proper goal setting, educating the patient that this treatment is not equivalent to emergency injections, and repeatedly recommending LAI therapy. Adherence can be improved by ensuring samples are available in the clinical setting at all times.

Hospitalization resource utilization and costs among Medicaid insured patients with schizophrenia with different treatment durations of long-acting injectable antipsychotic therapy.

This study evaluated the impact of using long-acting injectable (LAI) antipsychotics for a longer treatment duration versus a short duration on health care resource utilization among Medicaid-insured schizophrenia patients. Schizophrenia patients 13 years or older initiating LAI antipsychotics were identified from the Truven Health Analytics MarketScan Research Medicaid database between July 1, 2005, and June 30, 2010. The study population was grouped into 2 study cohorts (longer-usage-duration cohort: ≥ 180 days of supply and short-usage-duration cohort: <180 days of supply). Hospitalization-related resource utilization and costs were determined during a variable follow-up period and compared at the unadjusted and adjusted levels. Of the 5694 patients identified, 2838 patients were treated with LAI antipsychotics for a mean duration of 604 (SD, 432) days (mean age, 38.91 years), and 2856 were treated for 86 (SD, 43) days (mean age, 39.96 days). Total hospital lengths of stay, all cause (6.56 [SD, 18.63] vs 4.93 [SD, 13.40] days, P < 0.001) and schizophrenia related (5.18 [SD, 14.96] vs 4.16 [SD, 11.94] days, P = 0.005), and the mean number of hospitalizations, all cause (0.79 [SD, 1.78] vs 0.61 [SD, 1.41], P < 0.001) and schizophrenia related (0.63 [SD, 1.55] vs 0.51 [SD, 1.26], P = 0.001), were lower for the longer-usage-duration cohort. Cox regression results showed that using LAI antipsychotics for a longer duration was correlated with longer time to the first hospitalization for any cause and for schizophrenia. After multivariate regression, longer usage duration of LAI antipsychotics was associated with a decreased number of hospitalizations (-0.15 per year, P < 0.001), a decreased hospital length of stay (-1.50 days, P < 0.001), and reduced hospital payment (-26%, P < 0.001). Patients who are treated with LAI antipsychotics for a longer versus shorter duration use hospital resources less.

Patient and prescriber perspectives on long-acting injectable (LAI) antipsychotics and analysis of in-office discussion regarding LAI treatment for schizophrenia.

BACKGROUND: The research goal is to better understand prescriber, patient, and caregiver perspectives about long-acting injectable (LAI) antipsychotic therapy and how these perspectives affect LAI use. Addressing these perspectives in the clinic may lead to greater success in achieving therapeutic goals for the patient with schizophrenia. METHODS: Ethnographic information was collected from a non-random sample of 69 prescriber-patient conversations (60 with community mental health center [CMHC] psychiatrists; 9 with nurse-practitioners) recorded during treatment visits from August 2011 to February 2012, transcribed and analyzed. Discussions were categorized according to 11 predetermined CMHC topics. In-person observations were also conducted at 4 CMHCs, including home visits by researchers (n = 15 patients) prior to the CMHC visit and observations of patients receiving injections and interacting with staff. Telephone in-depth interviews with psychiatrists, patients, and caregivers to gather additional information on LAI discussion, prescription, or use were conducted. RESULTS: Antipsychotic treatment decisions were made without patient or caregiver input in 40 of 60 (67%) of psychiatrist-patient conversations. Involvement of patients or caregivers in treatment decisions was greater when discussing LAI (15 of 60 [25%]) vs oral antipsychotic treatment (5 of 60 [8%]). LAIs were not discussed by psychiatrists in 11 of 22 (50%) patients taking oral antipsychotics. When offered, more LAI-naïve patients expressed neutral (9 of 19 [47%]) rather than favorable (3 of 19 [16%]) or unfavorable (7 of 19 [37%]) responses. Prescribers were most concerned about potentially damaging the therapeutic relationship and side-effects when discussing LAIs while patient resistance was often related to negative feelings about injections. Psychiatrists had some success in overcoming patient objections to LAIs by addressing and decomposing initial resistance. More than half (11 of 19 [58%]) of LAI-naïve patients agreed to start LAI treatment following office visits. Patient-described benefits of LAIs vs orals included perceived rapid symptom improvement and greater overall efficacy. CONCLUSIONS: In this study, many psychiatrists did not offer LAIs and most patients and caregivers were not involved in antipsychotic treatment decision making. Opportunities to increase active patient engagement, address resistances, guide patient drug-formulation selection, and provide better LAI-relevant information for more individualized approaches to treating the patient with schizophrenia were present.

Impact on healthcare resource usage and costs among Medicaid-insured schizophrenia patients after initiation of treatment with long-acting injectable antipsychotics.

OBJECTIVE: This study compared healthcare resource usage and costs before and after initiating LAI antipsychotics among Medicaid-insured schizophrenia patients. METHODS: Schizophrenia patients ≥13 years of age initiating LAI antipsychotics were identified from the Thomson Reuters MarketScan® Research Medicaid database between 7/1/2005 and 6/30/2010. Patients were required to have 6 months of continuous medical/prescription drug coverage prior to LAI initiation (baseline period) and during a variable follow-up period. Annualized healthcare resource usage and costs for the baseline and follow-up periods were determined and compared. RESULTS: Among 5694 eligible patients, 55% were male and 45% were female, and the majority of the population was between the ages of 18-55 (86%). The study population had low general comorbidity, as assessed by the Charlson Comorbidity Index (CCI). Diabetes (17%) and chronic pulmonary disease (14%) were the most prevalent comorbidities. In comparison to the baseline period, during the follow-up period (mean duration = 25.7 months) the mean number of hospitalizations, all cause (1.52 ± 2.41 vs 0.70 ± 1.61, p < 0.001) and schizophrenia-related (1.21 ± 2.04 vs 0.57 ± 1.41, p < 0.001) declined as well as hospital lengths of stay (all cause: 14.77 ± 28.61 vs 5.75 ± 16.26 days, p < 0.001; schizophrenia-related: 12.39 ± 25.86 vs 4.67 ± 13.54 days, p < 0.001). As a result, annualized hospital payments were much lower (all cause: $16,249 ± $36,404 vs $7380 ± $21,087, p < 0.001; schizophrenia-related: $13,388 ± $31,614 vs $5645 ± $15,767, p < 0.001). LIMITATIONS: This study attempted to minimize the impact of differences in patient characteristics by having patients serve as their own controls in the before vs after comparison, however one still may not be able to account for all confounders in this non-randomized study population. CONCLUSION: For patients with schizophrenia who initiate LAI antipsychotic therapy, there is an improvement in disease management based on fewer hospitalizations for relapses, which is also associated with a marked reduction in healthcare costs.

Open-label study of the effect of combination quetiapine/lithium therapy on lithium pharmacokinetics and tolerability.

OBJECTIVE: The aim of this study was to assess the effect of oral quetiapine on the steady-state pharmacokinetics of lithium. METHODS: This was an open-label trial in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who had demonstrated tolerability to combination lithium/ antipsychotic therapy. Patients received lithium for at least 1 week before screening and throughout the 18-day trial. Quetiapine was coadministered in fixed, stepwise, increasing doses of 25 to 250 mg TID on days 4 through 11, and maintained at 250 mg TID on days 12 through 14. Blood samples were drawn to monitor plasma concentrations of lithium and quetiapine. Psychiatric assessments included the Brief Psychiatric Rating Scale, the Clinical Global Impression severity of illness item, and the modified Scale for the Assessment of Negative Symptoms. Neurologic function was assessed using the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Other assessments included clinical laboratory testing, electrocardiography, physical examinations, and monitoring for spontaneously reported adverse events. RESULTS: Nine men and 1 woman (mean [SE] age, 32.8 [1.9] years; mean [SE] body weight, 87.6 [3.3] kg) entered and completed the 18-day trial. Eight patients had bipolar disorder, 1 had paranoid schizophrenia, and 1 had schizoaffective disorder. Morning trough concentrations of lithium in serum (days 2, 6, 8, 10, 12, 14, and 17), as well as quetiapine and 2 of its metabolites in plasma (days 12, 13, and 14), did not appear to vary noticeably. Small increases were observed in the mean values of the area under the 12-hour serum lithium concentration-time curve and the maximum and minimum observed serum lithium concentrations when quetiapine was added to the lithium regimen. However, the increases were not considered clinically relevant by the investigators and were not statistically significant. A total of 91 adverse events were reported, 67 (73.6%) of which were not attributed to trial treatment. The most commonly reported adverse events during coadministration of lithium and quetiapine were somnolence (90.0% [9/10]), asthenia (70.0% [7/10]), dry mouth (30.0% [3/10]), nausea (30.0% [3/10]), vomiting (30.0% [3/10]), dizziness (30.0% [3/10]), tremor (30.0% [3/10]), and insomnia (20.0% [2/10]). There were no serious adverse events. CONCLUSIONS: Measures of lithium and quetiapine concentrations did not vary significantly during combination therapy. Coadministered lithium and quetiapine were well tolerated in the patients studied.

The safety and pharmacokinetics of quetiapine when coadministered with haloperidol, risperidone, or thioridazine.

The effects of haloperidol, risperidone, and thioridazine on the pharmacokinetics and side-effect profile of quetiapine were investigated in 36 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a single-center, two-period, multiple-dose, open-label, randomized trial. Over a one-to two-week period, quetiapine doses were escalated to 300 mg twice daily (bid). Patients were then treated for at least 7 days at the target quetiapine dose and subsequently entered into the combination therapy period, receiving haloperidol (7.5 mg, bid), risperidone (3 mg, bid), or thioridazine (200 mg, bid) for 8.5 days (after 3 days of dose escalation). Key assessments included the pharmacokinetics of quetiapine at steady state (area under the curve within a dosing interval [AUCtSS], maximum [CmaxSS], and minimum [CminSS] observed plasma concentrations, and oral clearance [Cl/f]), as well as the UKU Side Effect Rating Scale scores and safety evaluations. Neither risperidone nor haloperidol had significant effects on quetiapine pharmacokinetics. However, thioridazine produced statistically significant changes, decreasing the least squares means values of the AUCtSS, CmaxSS, and CminSS by 40%, 47%, and 31%, respectively, and increasing Cl/f by 68%. Increases in the following adverse events were noted during coadministration: somnolence (risperidone), insomnia and dry mouth (all three coadministered therapies), and dizziness (thioridazine). UKU side effect items that became worse in >or= 25% of patients during each coadministration period included sedation and increased sleep duration. Results of laboratory tests, electrocardiograms, and vital sign measurements revealed few clinically important changes. Clinical stability can be maintained with good tolerability during the transition from quetiapine monotherapy to periods of coadministration with haloperidol, risperidone, or thioridazine. Coadministration of either haloperidol or risperidone did not have any important effects on the steady-state pharmacokinetics of quetiapine. Thioridazine significantly increased the oral clearance of quetiapine. Increased doses of quetiapine may be necessary to control psychotic symptoms when thioridazine is coadministered with quetiapine.