Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.

4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.

S.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.

Teva Branded Pharmaceutical Products R&D, Inc.

This post hoc analysis investigated efficacy and tolerability of adjunctive cariprazine (CAR) in patients with major depressive disorder (MDD) using evidence-based medicine metrics of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).

Data sources were five completed Phase II/III, 6-8 week, randomized, double-blind, placebo-controlled studies. Efficacy outcomes included acute response (≥50% decrease from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS] total score). Tolerability outcomes included commonly occurring adverse events (AEs) and rates of discontinuation because of an AE, with data pooled across all studies for the CAR 1-2 mg/day plus 1.5 mg/day dose groups, 2-4.5 mg/day plus 3 mg/day dose groups, and for all groups where CAR dose was ≥1 mg/day. NNT and NNH were calculated for adjunctive CAR vs. adjunctive placebo.

MADRS response rates at Week 8 for CAR 2-4.5 mg/day vs. placebo were 134/271 (49.4%) vs. 101/264 (38.3%), resulting in a NNT of 9 (95% CI 6-36). In study NCT03738215, MADRS response rates at Week 6 for CAR 1.5 mg/day vs. placebo were 110/250 (44.0%) vs. 87/249 (34.9%), resulting in a NNT of 11 (95% CI 6-193). For the pooled CAR ≥1 mg/day group, MADRS response rates at Week 6 were 765/1887 (40.5%) for CAR vs. 354/1101 (32.2%) for placebo, resulting in a NNT of 12 (95% CI 9-21). For the pooled CAR ≥1 mg/day group, rates of akathisia vs. placebo were 209/1893 (11.0%) vs. 25/1108 (2.3%) for placebo, resulting in a NNH of 12 (95% CI 10-14). This appears dose related as the NNH for akathisia vs. placebo was 24 (95% CI 17-43) for the 1-2 mg/day plus 1.5 mg/day dose groups, and 9 (95% CI 7-11) for the 2-4.5 mg/day plus 3 mg/day dose groups. For the pooled CAR ≥1 mg/day group, rates of discontinuation because of an AE vs. placebo were 122/1893 (6.4%) vs. 26/1108 (2.3%) for placebo, resulting in a NNH of 25 (95% CI 19-38). This appears dose related as the NNH for discontinuation because of an AE vs. placebo was 94 (ns) for the 1-2 mg/day plus 1.5 mg/day dose groups, and 17 (95% CI 13-28) for the 2-4.5 mg/day plus 3 mg/day dose groups. For the pooled CAR ≥1 mg/d group, rates of weight gain ≥7% from baseline vs. placebo were 35/1893 (1.8%) vs. 12/1108 (1.1%) for placebo, resulting in a NNH of 131 (ns). LHH comparing MADRS response vs. discontinuation because of an AE is >1, and >>1 for the lower dose range. Indirect comparisons of the above results with that of the effect sizes seen in positive studies of other adjunctive antipsychotic treatments vs. adjunctive placebo in MDD demonstrate similar values for NNT for response, and when the lower dose range of CAR is used, a more favorable NNH regarding discontinuation because of an AE.

The benefit-risk profile of CAR is favorable for adjunctive treatment of MDD.

AbbVie

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.

Four experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.

S.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.

Teva Branded Pharmaceutical Products R&D, Inc.

To design and develop a new, innovative and valid School Menu Healthiness Assessment Tool that is suitable for the quantitative and qualitative analysis of school food and drink provision. Secondly, to analyse primary and secondary school menus and price lists pan-Wales to ascertain their healthiness and whether free school meal eligible pupils can afford to access healthy, nutritious food across the school day.

Codable items and categories of school food and drink provision were operationalised before the tool underwent iterative development and testing. Then, cross-sectional content analysis of publicly available documents detailing school food provision (i.e., menus and price lists).

Primary and secondary schools in Wales, United Kingdom.

In total, 82 canteen menus were sourced online. This comprised local authority catering for primary (n 22) and secondary (n 19) schools plus school-organised catering for primary (n 5) and secondary (n 36) schools.

Intercoder reliability testing found high agreeability between coders, demonstrating that the tool and data interpretation are reproducible and trustworthy. The free school meal allowance is not wholly sufficient for all secondary school pupils to purchase a healthy meal from the school canteen. Moreover, the tool identified that oily fish and wholegrain provision were lacking across many menus.

A valuable tool was created, useful for researchers and other health professionals (i.e., dietitians) who are required to analyse the healthiness of school food provision in line with the latest nutritional requirements. This study provides insight into the current school food and drink landscape pan-Wales.

One of the most relevant risk factors for suicide is the presence of previous attempts. The symptomatic profile of people who reattempt suicide deserves attention. Network analysis is a promising tool to study this field.

To analyze the symptomatic network of patients who have attempted suicide recently and compare networks of people with several attempts and people with just one at baseline.

1043 adult participants from the Spanish cohort “SURVIVE” were part of this study. Participants were classified into two groups: single attempt group (n = 390) and reattempt group (n = 653). Different network analyses were carried out to study the relationships between suicidal ideation, behavior, psychiatric symptoms, diagnoses, childhood trauma, and impulsivity. A general network and one for each subgroup were estimated.

People with several suicide attempts at baseline scored significantly higher across all clinical scales. The symptomatic networks were equivalent in both groups of patients (p > .05). Although there were no overall differences between the networks, some nodes were more relevant according to group belonging.

People with a history of previous attempts have greater psychiatric symptom severity but the relationships between risk factors show the same structure when compared with the single attempt group. All risk factors deserve attention regardless of the number of attempts, but assessments can be adjusted to better monitor the occurrence of reattempts.

Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.

In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.

In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.

Four recommendations are formulated for further research and clinical implementation.

Patient-reported outcomes (PROs) are increasingly collected in clinical trials and real-world studies as they provide valuable information on the impact of a treatment from the patient’s perspective. Studies in Parkinson’s disease psychosis (PDP) have focused on hallucination and delusions, however individuals with PDP also face functional limitations associated with worsening psychosis. Assessing activities of daily living (ADLs) and functioning of PDP patients can help inform PDP treatment. The International Parkinson and Movement Disorder Society has recommended the use of the Functional Status Questionnaire (FSQ) which has been infrequently utilized. Prior results were reported from a Phase 4 open-label study examining the impact of pimavanserin on ADLs and functioning in patients with PDP which utilized a modified version of the FSQ (mFSQ) as the primary outcome measure. In this analysis, we provide additional data on the patient-reported mFSQ within specific domains and correlation to the Schwab & England ADL scale.

Eligible patients entered a 16-week single-arm, open-label study of once-daily oral pimvanserin (34mg). The 6 domain FSQ was modified to assess 5 domains by removing the work/performance domain since this was not applicable to the patients in this study. The mean change from baseline to week 16 was evaluated in mFSQ domains (Basic ADL, Intermediate ADL, Psychological Function, Quality of Interaction, Social Activity). In addition, correlation between Schwab & England ADL scale and observed mFSQ value across post-Baseline visits were evaluated.

A total of 29 patients were enrolled in the study, mean age (70.2 years), 62% males. The MMRM LSM (SE) for mSFQ from baseline to Week 16 were the following within each domain: Basic ADL (n=22), 8.1 (2.41), p=0.0031; Intermediate ADL (n=21), 7.0 (3.00), p=0.0286; Psychological Function (n=22), 13.3 (1.94), p <.0001; Quality of Interaction (n=22), 12.3(2.07), p <.0001; and Social Activity (n=18), 25.8 (7.52), p=0.0026. All mFSQ domains were showing improvement at 16 weeks from baseline; however, the largest change was seen in Social Activity. The correlation of mFSQ and the Schwab & England ADL scales resulted in a correlation coefficient of r=0.6 (p <.0001) for patient total score and r=0.5 (p<.0001) for caregiver total score. There was a consistent trend among both scales which was demonstrating improvement among patients and caregivers.

This was the first open-label clinical trial to utilize the mFSQ in patients with PDP. In this small, proof-of-concept study, treatment with pimavanserin was associated with improvement across all mFSQ domains; most improvement was seen in social activity. Additionally, the mFSQ was significantly correlated with the Schwab & England ADL, thus this appears to be a promising scale deserving of further evaluation and use in clinical studies as well as in the clinic to complement other assessments.

Acadia Pharmaceuticals, Inc.

The DSM V-TR places video game addiction, also known as Internet Gaming Disorder (IGD) within the section that suggests the need for additional research. Simultaneously, there has been a remarkable surge in the consumption of video games, with this medium attracting more funding than ever before. Additionally, as this disorder gains increased attention from the psychiatric world, there is a lack of any formal guidelines on the treatment of IGD, or for the superiority of any specific pharmaceutical treatment. The aim of this project focuses on reviewing the neurobiological mechanisms involved in IGD in order to garner a more robust understanding of the neural pathways involved.

Google Scholar and PubMed were explored using search terms including “Internet gaming disorder,” “neurology,” “imaging,” “mechanisms,” and “comorbid” in various permutations. Thirty-seven articles were included from 100 search results that addressed IGD neural and biological mechanisms, and their potential comorbidity with other mental disorders.

The literature suggests that some of the neural findings in IGD are similar to those found in other addiction disorders, which include the following mechanisms: (i) Activation of brain regions associated with reward, as observed in cue exposure and craving studies. Neurotransmitter system studies further suggest the involvement of dopamine-mediated reward mechanisms. (ii) Decreased activity in areas responsible for impulse control and impaired decision-making. (iii) Reduced functional connectivity in brain networks related to cognitive control, executive function, motivation, and reward. Another study suggested that the severity of IGD and depression symptoms predict each other reciprocally. Neurologically, individuals with IGD exhibited enhanced rsFC between the left amygdala and the right dorsolateral prefrontal cortex, inferior frontal gyrus, and precentral gyrus compared to control participants. The baseline amygdala-frontoparietal connectivity negatively predicted the reduction in depression symptoms following a psychotherapy intervention. Other studies suggest that altered executive control mechanisms in attention deficit hyperactivity disorder (ADHD) would be a predisposition for developing IGD. Furthermore, according to the literature, it was indicated that engaging in Internet game playing was linked to reduced white matter density in brain areas responsible for decision-making, inhibiting behavior, and regulating emotions.

The literature findings regarding IGD’s neural and biological pathways, as well as the association of these findings with other disorders such as depressive disorders and ADHD reflect behavioral patterns in individuals with IGD. These mechanisms can be utilized to maximize behavioral and pharmaceutical interventions.

No Funding

Centanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) in development for treatment of attention-deficit/hyperactivity disorder (ADHD). The effect of CTN on cardiac repolarization from a thorough QT (TQT) trial is reported.

In this double-blind, placebo (PBO)- and active-controlled, 3-period crossover TQT trial, healthy adults (18-65 years) were randomized to dosing sequences including CTN (800 mg supratherapeutic dose: 4 x 100 mg tablets in the morning and 5 hours later), CTN PBO (4 PBO tablets in the morning and 5 hours later), and active control moxifloxacin (400 mg + CTN PBO in the morning and CTN PBO 5 hours later). Morning doses were separated by 72 hours. Plasma was collected and data were extracted from continuously recorded ECGs for 24 hours following dosing. Effects on ECG parameters (QT interval with Fridericia correction factor [QTcF], PR and QRS intervals, and T- and U-wave morphology), and heart rate (HR) were assessed. The primary analysis was C-QTc, the relationship between drug concentration and PBO-corrected change from baseline in QTcF (ΔΔQTcF). Categorical analyses of ECG parameters were conducted for changes in QTcF, PR, and QRS intervals and in HR.

Of 30 participants enrolled, 56.7% were male and 86.7% were White. Mean (SD) age was 37.6 (14.5) years; mean (SD) BMI was 26.4 (3.4) kg/m2. The slope (90% CI) of the C-QTc relationship for CTN was −0.001 (−0.003, 0.00002) msec/[ng/mL] and not significant. The predicted ΔΔQTcF (90% CI) at the geometric mean Cmax of CTN 800 mg was −2.72 (−6.92, 1.48) msec. A significant slope (90% CI) of the C-QTc relationship for moxifloxacin (0.004 [0.002, 0.006] msec/[ng/mL]) and a predicted ΔΔQTcF (90% CI) at the geometric mean Cmax of moxifloxacin 400 mg above 5 msec (11.75 [8.25, 15.24]) confirmed assay sensitivity. No ΔΔQTcF ≥10 msec was observed for CTN at any postdose time point; all upper limits of 90% CIs of ΔΔQTcF were <10 msec. The by-time-point analysis showed the maximum least squares mean difference in ΔQTcF (90% CI) between CTN and PBO was 1.64 (−1.40, 4.68) msec at 24 hours postdose. No CTN-treated participants had a QTcF increase of >30 msec; no relevant increases in PR or QRS interval or HR were observed. Four participants had >25% decrease in HR and <50 beats per minute. No abnormal U waves were observed; 1 participant had abnormal T-wave morphology. No serious TEAEs or deaths were reported. The most frequently reported TEAEs with CTN were nausea (24.1%), dizziness (24.1%), and decreased appetite (13.8%).

In this TQT trial, centanafadine, a potential first-in-class NDSRI in development for treatment of ADHD, had no clinically meaningful effect on cardiac repolarization and was generally safe and well tolerated.

Previous presentation: 2023 ACCP Annual Meeting, September 10–12, 2023, Bellevue, WA

Otsuka

This study examined whether curriculum based continuing medical education (CME) interventions can improve provider knowledge, competence, and confidence related to the assessment and treatment of patients with major depressive disorder (MDD).

The online CME curriculum consisted of 2 online activities, which used repeated pairs pre-/post-assessment study design and McNemar’s test (P <.05 is considered significant) to assess educational effect. Clinicians who completed questions both pre- and post-assessment were aggregated across activities, stratified by 2 learning themes.

Significant improvements (n=31-756, P<0.05-0.001) were seen for knowledge/competence across all providers (psychiatrists, psychiatry NPs, psychiatry PAs, PCPs, primary care NPs, and primary care PAs) for both learning themes – “Appropriate depression medication selection and modification” and “Evaluating residual symptoms in patients with MDD”. Notable improvements:

• • There was a 48% relative improvement among PCPs, 26% relative improvement among primary care NPs, 42% relative improvement among primary care PAs, 19% relative improvement among psychiatrists, 23% relative improvement among psychiatry NPs, and 24% relative improvement among psychiatry PAs (P<0.001) related to appropriate depression medication selection and modification.

• • There was a 47% relative improvement among PCPs (P<0.01), 41% relative improvement among NPs (P<0.01), 18% relative improvement among psychiatrists, 33% relative improvement among psychiatry NPs, and 52% among psychiatry PAs (P<0.001) related to evaluating residual symptoms in patients with MDD.

Participation in CME interventions significantly improved knowledge/competence and confidence among psychiatric and primary care providers. This study identified persistent gaps in clinician knowledge and competence related to MDD care that may guide future education.

Medscape Education, Takeda Pharmaceuticals

Schizophrenia is a chronic neurodevelopmental disorder characterized by positive, negative, and cognitive symptoms. While current antipsychotic (AP) medications are generally effective in treating positive symptoms, they don’t effectively manage the negative symptoms of schizophrenia (NSS). This study examined the healthcare resource utilization (HCRU) and cost among patients with NSS in the United States.

This retrospective longitudinal observational study utilized de-identified administrative claims data from STATinMED RWD Insights (01/01/2016-09/30/2022). Study sample included patients with schizophrenia identified using ICD-10-CM: F20.XX, diagnosed with NSS (cases; ICD-10-CM: F20.5; index=first NSS diagnosis) or not (controls; random date assigned as index); identification period: 01/01/2017-09/30/2021. Patients were 13 years or older at index, had 12-month of continuous capture data pre-(baseline) and post-(follow-up) index date, and had evidence of AP use at baseline. Outcomes were prevalence of NSS, mental health (MH)-related, schizophrenia-related, and all-cause HCRU and costs per patient per year (PPPY). Patients’ demographic, clinical characteristics, and other psychiatry and neurodevelopmental comorbidities were assessed at baseline. Unadjusted and Inverse Proportional Treatment Weighted (IPTW) comparison were conducted for baseline characteristics and outcomes followed by Generalized Linear Models (GLMs) for HCRU and costs.

The final study sample had 5,691 NSS and 236,895 non-NSS patients. Prevalence rate of NSS was estimated at 24.66 per 1000 patients of Schizophrenia. Patients with NSS were significantly older (mean: 50 vs 48 years), less commercially insured (10% vs 15%), and had greater comorbidities including alcohol abuse (12% vs 8%), depression (30% vs 24%), diabetes without chronic complications (22% vs 17%), drug abuse (21% vs 16%), uncomplicated hypertension (41% vs 32%), and psychoses (80% vs 58%); all p-values<0.001. After controlling for baseline characteristics, patients with NSS had significantly higher all-cause inpatient admissions (mean: 5.2 vs 4.2), outpatient emergency room (ER) visits (mean: 2.8 vs 2.0), inpatient stay costs ($23,830 vs $20,669), outpatient ER visit costs ($1,738 vs $1,167.20) and less prescriptions (mean: 49.2 vs 51.4); all p-values<0.05. GLM analysis also showed patients with NSS had significantly higher all-cause inpatient admissions (mean: 4.8 vs 3.7), number of outpatient visits (mean: 14.3 vs 13.8), and inpatient stay costs ($20,853 vs $17,809); all p-values<0.05. MH- and schizophrenia-related HCRU and costs PPPY were consistent with all-cause HCRU and cost results.

Patients with predominant NSS had higher HCRU and healthcare costs compared to patients without predominant NSS. New therapies that improve negative symptoms may reduce the burden of schizophrenia.

Sumitomo Pharma America (formerly Sunovion Pharmaceuticals Inc).

Bipolar disorder (BD) is a lifelong mental disorder with a variable course, comprising one of the primary psychiatric illnesses warranting hospitalization due to its recurrent and chronic nature. Despite the existence of extensive evidence regarding factors influencing psychiatric hospitalization duration, limited scientific evidence establishes the duration of psychiatric hospitalization in patients with BD. The objective of this study is to assess the clinical characteristics and factors influencing the duration of hospital stay in patients with BD.

This is a retrospective observational and descriptive study. The protocol was approved by the ethics and research committee of the Hospital Universitario "Dr. José Eleuterio Gonzalez” in Monterrey, Nuevo León, México under the name "Factores predictores del tiempo de hospitalización psiquiátrica en pacientes con trastorno bipolar". Retrospective investigation was carried out of patients admitted between July 2015 and May 2022. Clinical and sociodemographic characteristics of 276 patients diagnosed with BD type 1 and type 2 were collected. Descriptive analyses were conducted for all variables using frequencies and percentages for categorical variables. Typical dispersion measures were applied to quantitative variables. Mann-Whitney U test was used to compare means between groups for dichotomous variables, and the Kruskal-Wallis test for variables with more than two categories. Spearman’s correlation coefficient was used for quantitative variables. Statistically significant values were considered at p < 0.05.

Factors associated with longer hospital stay included younger age (p < 0.001), being separated or divorced (p = 0.002), unemployment (x=27.94 vs. x=23.77; p=0.12), absence of medical comorbidity (x=27.21 vs. x=20.73; p=0.11), previous hospitalization history (x=28.50 vs. x=23.26; p=0.005), history of substance abuse (x=28.55 vs. 24.68; p=0.26), use of pharmacological restraint (p=0.28), and non-use of mood stabilizers during hospitalization (x=27.54 vs. x=24.11; p=0.27).

Overall, this study highlights the significance of comprehensive and personalized treatment approaches for patients with bipolar disorder. By addressing specific risk factors and optimizing therapeutic strategies, healthcare professionals can potentially reduce the length of hospital stays, leading to improved patient well-being and resource utilization within psychiatric care facilities. However, further research and intervention studies are warranted to validate and implement these findings in clinical practice.

No Funding

Valbenazine is a highly selective vesicular monoamine transporter 2 inhibitor indicated for tardive dyskinesia (TD), a persistent and potentially debilitating movement disorder associated with prolonged antipsychotic exposure. Given the paucity of data regarding the course of TD in patients no longer taking antipsychotics, a meta-analysis of 3 long-term valbenazine studies was conducted in subgroups with and without concomitant antipsychotic use at baseline.

KINECTTM-3 (NCT02274558), KINECTTM-4 (NCT02405091), and JKINECT (NCT03176771) data were analyzed in study completers taking antipsychotics at baseline (AP+) and those who were not (AP-). The Abnormal Involuntary Movement Scale (AIMS) total score was used to measure TD severity at baseline, Wk48 (end of valbenazine treatment), and Wk52 (4 weeks after valbenazine withdrawal). The meta-analysis implemented a random-effects model that weighted each study based on inverse variance, adjusted for between-study variance.

Of 576 enrolled patients, 336 (58.3%) were study completers and included for analysis: AP+ (n=269); AP- (n=67). Mean baseline AIMS scores ranged from 7.9–14.9 (AP+) and 10.9–14.5 (AP-). Mean changes from baseline in AIMS scores indicated substantial TD improvements with valbenazine at Wk48 (AP+, 6.1; AP-, -6.5) and return towards baseline severity at Wk52 (AP+, -2.1; AP-, -1.4).

Once-daily valbenazine treatment resulted in substantial and sustained TD improvement through Wk48, with no meaningful differences between AP+ and AP- subgroups. The return towards baseline severity after valbenazine withdrawal shows TD is chronic and often irreversible, even in patients no longer taking antipsychotics. Continuous treatment with valbenazine may be warranted irrespective of antipsychotic therapy.

Neurocrine Biosciences, Inc.