Chorea is defined as a hyperactive movement disorder associated with involuntary, quick, and unpredictable muscle contractions of the limbs, face, and trunk. The unpredictable nature of these movements includes variation in speed, timing, and direction of movement. A wide variety of medications, medical conditions and illicit drugs have been associated with movement disorders. Examples include a multitude of antipsychotic induced movement disorders and dyskinesia related to dopaminergic agents, like levodopa and metoclopramide. Dyskinesias have been associated with psycho-stimulant use, such as methylphenidate. However, most cases reported were associated with large doses or chronic use. Aside from dyskinesia, methylphenidate is known to be associated with tic disorder, tremor, and muscle spasm. However, this case reported is unlike any of the above described and involved the development of chorea after only 2 days of moderate doses of methylphenidate, in a patient on chronic methadone maintenance treatment, with successful arrest of symptoms following discontinuation of the methylphenidate.

A 47-year-old female was admitted to our hospital after presenting to the emergency department with 1 week of violent flailing movements. The ballistic flailing movements started acutely after 2 days of initiating methylphenidate in addition to her chronic methadone treatment and 2-week period of initiation of paroxetine. Lab work showed normal CBC, CMP, CRP, CK, and TSH. Urine drug screen, CT angiography of the head, and Huntington’s disease testing were all unremarkable, suggesting a decreased likelihood of illicit drugs, traumatic brain injury, or Huntington’s disease etiologies. Confirmation of the diagnosis was made as the chorea symptoms abruptly resolved upon discontinuation of methylphenidate and administration of intravenous Benadryl. The patient has been on methadone alone for 11 months and methylphenidate alone 2 years back with no involuntary movements or any similar presentation that shows the possibility of drug interaction through cytochrome P450 metabolism between Methylphenidate and methadone.

We are presenting a rare case report that adds on to the scarce literature on methylphenidate-induced chorea. It also challenges the consulting psychiatrists to broaden their differential diagnosis for acute onset of choreiform movement disorders. This unique case intrigues the thought process to consider the interaction of methylphenidate in the presence of cytochrome P450 2D6 and 3A4 inhibitors like methadone.

Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients.

Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed.

During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm (p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported.

Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.

Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG.

Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria.

We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis.

Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations.

Conventional treatment methods have limited effectiveness in addressing late-life depression (LLD) that does not respond well. While a new approach called priming repetitive transcranial magnetic stimulation (rTMS) has shown promise in treating depression in adults, its effectiveness in LLD has not been explored. This study aimed to investigate the impact of priming rTMS on LLD.

This study investigated the effectiveness of priming rTMS in 31 patients with LLD who did not improve after an adequate trial of antidepressants. Patients were randomly assigned to receive either active priming rTMS or sham priming rTMS. Active priming rTMS was delivered over the right dorsolateral prefrontal cortex for 10 sessions, lasting 31 minutes each, over a period of 2 weeks.

The group receiving active priming rTMS demonstrated greater improvements in scores on the Hamilton Rating Scale for Depression (p < 0.037; partial η2 0.141) and the Geriatric Depression Rating Scale (p < 0.045; partial η2 0.131) compared to the sham priming group, with a mild effect size. At the end of the second and fourth weeks, the priming rTMS group achieved a response rate of 50%, while the sham priming group had response rates of 26.7% and 6.7%, respectively. No adverse effects requiring intervention were observed.

Priming rTMS is well-tolerated for the treatment of LLD and not only reduces the severity of depression but also maintains the achieved response over time.

Deutetrabenazine is FDA-approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal trials (ARM-TD/AIM-TD), deutetrabenazine significantly improved Abnormal Involuntary Movement Scale (AIMS) scores and was well-tolerated. This post hoc analysis examined the efficacy and safety of long-term deutetrabenazine treatment in TD patients with comorbid psychiatric illness, including schizophrenia/schizoaffective disorder and mood disorders (bipolar/depression/other).

Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study. Deutetrabenazine was titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed in subgroups by comorbid psychiatric illness.

A total of 337 patients in the OLE study were included in the analysis: 205 patients with schizophrenia/schizoaffective disorder (mean age, 55 years; 50% male; 6.4 years since diagnosis; 92% taking DRA) and 131 patients with mood disorders (mean age, 60 years; 35% male; 4.6 years since diagnosis; 50% taking DRA). At week 145, mean ± SE dose was 40.4 ± 1.1 mg/day for schizophrenia/schizoaffective disorder (n = 88) and 38.5 ± 1.2 mg/day for mood disorders (n = 72). Mean ± SE change from baseline in AIMS score at week 145 was −6.3 ± 0.49 and −7.1 ± 0.58, 56% and 72% achieved PGIC treatment success, and 66% and 82% achieved CGIC treatment success in schizophrenia/schizoaffective disorder and mood disorder patients, respectively. Overall AE incidence (exposure-adjusted incidence rates [incidence/patient-years]) was low: any, 1.02 and 1.71; serious, 0.10 and 0.12; leading to discontinuation, 0.07 and 0.05).

Long-term deutetrabenazine treatment provided clinically meaningful improvements in TD-related movements, with a favorable safety profile, regardless of underlying comorbid psychiatric illness.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel

Dextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to determine whether DXM/BUP has alcohol and/or substance misuse liability.

We evaluated spontaneous reports of terms such as “alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse” in the FDA Adverse Event Reporting System (FAERS). The FAERS is a spontaneous reporting database of adverse events submitted to the FDA.

We performed a comparative assessment of the alcohol and/or substance misuse liability of DXM/BUP since its market authorization in August 2022, using acetaminophen as the control. Dextromethorphan served as the upper-bound reference point. Our findings showed that, since August 2022, dextromethorphan had a significant reporting odds ratio (ROR) for “drug abuse.” In contrast, DXM/BUP did not have a significant ROR for any of the categories of alcohol and/or substance misuse evaluated. Limitations of our findings derive largely from the limitations of the FAERS and its data capture method.

The absence of alcohol or substance misuse reported to the FAERS with DXM/BUP accords with the lack of evidence of abuse liability prior to FDA approval and its non-scheduling by the DEA.

To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery–Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD).

Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models.

In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (−12.8 [0.46] vs −10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044).

In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS.

ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

The Dextroamphetamine Transdermal System (d-ATS) was developed as an alternative to oral amphetamine (AMP) formulations for ADHD. In a pivotal study, d-ATS met primary and secondary efficacy endpoints for ADHD in children and adolescents. Study subjects wore d-ATS for 9 hours, and an improvement in Swanson, Kotkin, Agler, M-Flynn, and Pelham scale (SKAMP) total score was observed from 2 through 12 hours after application. Patients with ADHD may need varying durations of treatment for symptoms from day to day. This analysis describes the exposure-response (E-R) relationship for d-ATS and explores possible outcomes for wear times ≤9 hours under varying assumptions.

A population pharmacokinetic (PK) model was developed to describe AMP disposition following d-ATS administration. This model was used to construct a population pharmacokinetic/pharmacodynamic (PK/PD) model from SKAMP total score data from two pediatric clinical studies to characterize onset and duration of effect after d-ATS administration. The integrated PK/PD model was used to describe the d-ATS E-R relationship and simulate the potential onset and duration of effect of d-ATS in response to various removal times (when <9 hours) by utilizing SKAMP scores as the efficacy measure. Subject-level AMP PK and SKAMP profiles were simulated for d-ATS removal at 4–9 hours post-application under different assumptions for AMP absorption after early patch removal. Modifications were made to the original population PK model to simulate patch removal.

Data from 81 children and 41 adolescents, 6–17 years old, were included. The model provided a reasonable description of the SKAMP score over time, showing an initial decline ~2 hours after patch application. In approximately 50% of children and adolescents, the maximum decline in SKAMP scores was observed within the first 4 hours after patch application. Earlier simulated d-ATS removal times were associated with reduced systemic exposure and earlier return to near-baseline scores across the range of assumptions tested.

Under different assumptions, the graphs changed modestly but not dramatically. For example, with moderate/conservative assumptions, following a 9-hour wear time, SKAMP scores returned to within 90% of baseline value in ~49% of subjects by 12 hours and ~80% of subjects by 16 hours. Following a 4-hour wear time, percentages were ~74% by 12 hours and ~95% by 16 hours.

Simulation results suggest that the duration of d-ATS efficacy may be related to wear time, which can be adjusted according to treatment needs, consistent with published observations for another transdermal stimulant. The d-ATS patch provides the ability to control medication exposure by shortening wear time, allowing treatment duration to be individualized and optimized in ADHD patients who have varying schedules and needs.

Noven Pharmaceuticals, Inc.

Approximately 70% of patients with bipolar disorder (BPD) are initially misdiagnosed, resulting in significantly delayed diagnosis of 7–10 years on average. Misdiagnosis and diagnostic delay adversely affect health outcomes and lead to the use of inappropriate treatments. As depressive episodes and symptoms are the predominant symptom presentation in BPD, misdiagnosis as major depressive disorder (MDD) is common. Self-rated screening instruments for BPD exist but their length and reliance on past manic symptoms are barriers to implementation, especially in primary care settings where many of these patients initially present. We developed a brief, pragmatic bipolar I disorder (BPD-I) screening tool that not only screens for manic symptoms but also includes risk factors for BPD-I (eg, age of depression onset) to help clinicians reduce the misdiagnosis of BPD-I as MDD.

Existing questionnaires and risk factors were identified through a targeted literature search; a multidisciplinary panel of experts participated in 2 modified Delphi panels to select concepts thought to differentiate BPD-I from MDD. Individuals with self-reported BPD-I or MDD participated in cognitive debriefing interviews (N=12) to test and refine item wording. A multisite, cross-sectional, observational study was conducted to evaluate the screening tool’s predictive validity. Participants with clinical interview-confirmed diagnoses of BPD-I or MDD completed a draft 10-item screening tool and additional questionnaires/questions. Different combinations of item sets with various item permutations (eg, number of depressive episodes, age of onset) were simultaneously tested. The final combination of items and thresholds was selected based on multiple considerations including clinical validity, optimization of sensitivity and specificity, and pragmatism.

A total of 160 clinical interviews were conducted; 139 patients had clinical interview-confirmed BPD-I (n=67) or MDD (n=72). The screening tool was reduced from 10 to 6 items based on item-level analysis. When 4 items or more were endorsed (yes) in this analysis sample, the sensitivity of this tool for identifying patients with BPD-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. These properties represent an improvement over the Mood Disorder Questionnaire, while using >50% fewer items.

This new 6-item BPD-I screening tool serves to differentiate BPD-I from MDD in patients with depressive symptoms. Use of this tool can provide real-world guidance to primary care practitioners on whether more comprehensive assessment for BPD-I is warranted. Use of a brief and valid tool provides an opportunity to reduce misdiagnosis, improve treatment selection, and enhance health outcomes in busy clinical practices.

AbbVie Inc.

Trichotillomania (TTM) is a mental health disorder characterized by repetitive urges to pull out one’s hair. Cognitive deficits have been reported in people with TTM compared to controls; however, the current literature is sparse and inconclusive about affected domains. We aimed to synthesize research on cognitive functioning in TTM and investigate which cognitive domains are impaired.

After preregistration on the International Prospective Register of Systematic Reviews (PROSPERO), we conducted a comprehensive literature search for papers examining cognition in people with TTM versus controls using validated tests. A total of 793 papers were screened using preestablished inclusion/exclusion criteria, yielding 15 eligible studies. Random-effects meta-analysis was conducted for 12 cognitive domains.

Meta-analysis demonstrated significant deficits in motor inhibition and extradimensional (ED) shifting in people with TTM versus controls as measured by the stop-signal task (SST) (Hedge’s g = 0.45, [CI: 0.14, 0.75], p = .004) and ED set-shift task (g = 0.38, [CI: 0.13, 0.62], p = .003), respectively. There were no significant between-group differences in the other cognitive domains tested: verbal learning, intradimensional (ID) shifting, road map spatial ability, pattern recognition, nonverbal memory, executive planning, spatial span length, Stroop inhibition, Wisconsin card sorting, and visuospatial functioning. Findings were not significantly moderated by study quality scores.

Motor inhibition and ED set-shifting appear impaired in TTM. However, a cautious interpretation of results is necessary as samples were relatively small and frequently included comorbidities. Treatment interventions seeking to improve inhibitory control and cognitive flexibility merit exploration for TTM.

This study examines the impact of ethnic music culture inheritance and music education on anxiety levels among college students. Anxiety is a prevalent issue affecting college students. Exploring the potential influence of ethnic music culture and music education could provide insights into effective interventions to address anxiety among this population.

The study involved a sample of 200 college students from different ethnic backgrounds, aged 18 to 25, studying at a university. Participants were divided into two groups: the experimental group (n=100) and the control group (n=100). The experimental group received ethnic music culture inheritance classes and music education programs, while the control group proceeded with their regular curriculum. Assessments of anxiety levels were conducted using standardized psychological scales, including the State-Trait Anxiety Inventory (STAI) and the Depression, Anxiety, and Stress Scale (DASS). The intervention period lasted for one academic semester.

Analysis using SPSS23.0 showed that the experimental group, which received ethnic music culture inheritance and music education, exhibited significantly lower anxiety levels compared to the control group (P<0.001). Both the STAI and DASS scores demonstrated a 30% reduction in anxiety symptoms among the experimental group, indicating the positive impact of ethnic music culture inheritance and music education on reducing anxiety among college students.

The results show that incorporating ethnic music cultural inheritance and music education into university curricula can effectively reduce students’ anxiety levels. The integration of cultural elements and music education not only promotes the preservation of national music culture but also contributes to the mental health of students.

Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours. This phase 3 study evaluated the efficacy and safety of dasotraline in children with attention deficithyperactivity disorder (ADHD) throughout the day, in a laboratory classroom setting (NCT02734693).

Children (6–12 years) meeting DSM-5 criteria for ADHD were randomized to 2 weeks of dasotraline or placebo (dosed daily at home at approximately 8 PM). Following an abbreviated practice day, laboratory classroom evaluations took place at baseline and on Day 15. The primary endpoint was mean change from baseline at Day 15 in ADHD symptoms, as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Combined Score (SKAMP-CS), obtained from the average of 7 assessments collected across the 12-hour laboratory classroom day (12–24 hours post-dose). Secondary endpoints included SKAMP scores obtained throughout the day at individual timepoints from 8 AM through 8 PM (12–24 hours post-dose), and measures of safety and tolerability.

The ITT population comprised 112 patients. Mean age was 9.5 years, 68.8% were male; 92% completed the study. Dasotraline 4 mg/day significantly improved mean SKAMP-CS versus placebo (p<0.0001, effect size 0.85) with significant effects persisting throughout the day. Mean SKAMP subscores improved significantly versus placebo (Attention p<0.0001, effect size 0.81; Deportment p<0.001, effect size 0.70). Treatment-emergent adverse events were generally mild or moderate in severity; most frequent (with dasotraline 4 mg/day; placebo) included: insomnia (19.6%; 3.6%, all terms combined), decreased appetite (10.7%; 3.6%), headache (10.7%; 8.9%), affect lability (8.9%; 7.1%), irritability (5.4%; 3.6%), postural orthostatic tachycardia syndrome (5.4%; 0%), and perceptual disturbances (5.4%; 0%).

In this 2-week, randomized, double-blind, laboratory classroom study in children with ADHD, once-daily dasotraline significantly improved ADHD symptoms (including deportment and attention), compared with placebo, and demonstrated sustained efficacyup to 24 hours post-dose. The most common adverse events were insomnia, decreased appetite, and headache.

Study sponsored by Sunovion Pharmaceuticals Inc.

The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies.

The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria.

Of the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val–Val participants). There were insufficient nature and number of studies for meta-analysis.

The cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).

Patients with major depressive disorder (MDD) often have inadequate response to antidepressant treatment (ADT) requiring augmentation with other treatments. Cariprazine is a D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and manic, mixed, and depressive episodes of bipolar I disorder. The efficacy of cariprazine as an adjunctive treatment for patients with MDD and inadequate response to ADT alone has been evaluated in phase 2/3 randomized, double-blind, placebo-controlled trials. Post hoc analyses of one phase 3 trial (NCT03738215) evaluated cariprazine + ADT for improving depressive symptoms in subgroups of patients categorized by 1) the level of response to ongoing ADT at baseline and 2) the number of ADTs associated with inadequate response during the current episode.

Patients were randomized to placebo + ADT (n=254), cariprazine 1.5 mg/d + ADT (n=252), or cariprazine 3 mg/d + ADT (n=253) for 6 weeks of double-blind treatment. Post hoc analyses evaluated change from baseline to week 6 in MADRS total score in subgroups of patients who had ≥25%–<50% or <25% response to ongoing ADT at baseline, and in subgroups of patients who had inadequate response to 1 or ≥2 ADTs in the current episode. Analyses used a mixed-effects model for repeated measures; least squares mean differences (LSMD) versus placebo with 95% confidence interval (95% CI) were calculated.

At baseline, 65.1% (n=486) of patients had an ADT response level between 25%–<50% and 34.9% (n=261) of patients had an ADT response level <25%. Mean MADRS total score reductions were greater for cariprazine 1.5 mg/d + ADT versus placebo + ADT in both ADT response subgroups (25%–<50% ADT response: -14.8 vs -11.9, LSMD [95% CI]=-2.3 [-4.2, -0.3]; <25% response to ADT: (-14.7 vs -11.7, LSMD [95% CI]=-2.6 [-5.5, 0.3]). For cariprazine 3 mg/d + ADT, mean change in MADRS total score was numerically greater versus placebo in both response subgroups (25%–<50% response=-14.2, LSMD [95% CI]=-1.5 [-3.5, 0.4]; <25% response= -12.3, LSMD [95% CI]=-0.74 [-3.6, 2.1]). Approximately 86% (n=644) and 14% (n=105) of patients in this study had inadequate response to 1 ADT or ≥2 ADTs, respectively, during the current episode. The LSMD (95% CI) in MADRS total score change for cariprazine 1.5 mg/d + ADT versus placebo + ADT was -2.3 (-4.1, -0.6) in the subgroup of patients with 1 previous ADT and -3.2 [-7.1, 0.8]) in the subgroup of patients with ≥2 previous ADTs. For cariprazine 3 mg/d + ADT, the LSMD (95% CI) in MADRS total score change versus placebo was -0.7 (-2.5, 1.0) in the 1 previous ADT subgroup and -4.7 (-8.8, -0.6) in the ≥2 previous ADTs subgroup.

In these post hoc analyses, cariprazine + ADT was associated with greater reductions in MADRS total score versus placebo regardless of the level of response to ongoing ADT at baseline or number of prior ADT failures in the current episode.

AbbVie

Akathisia, a common side effect of psychotropic medications, poses a significant challenge in neuropsychiatry, affecting up to 30% of patients on antipsychotics. Despite its prevalence, akathisia remains poorly understood, with difficulties in diagnosis, patient reporting, and treatment efficacy. This research aimed to shed light on effective interventions to improve akathisia management.

A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, encompassing controlled trials in English and Italian languages. Databases, such asPubMed, Scopus, and EMBASE, were searched until July 9, 2023. Treatment effectiveness was assessed using standardized mean differences (SMDs) in post-treatment akathisia scores.

Thirteen studies involving 446 individuals met the inclusion criteria. Benzodiazepines, beta-blockers, and NaSSA demonstrated significant efficacy as compared with placebo. Anticholinergic, anticonvulsant, triptan, and other treatments did not show significant differences. Benzodiazepines ranked highest in P-scores (0.8186), followed by beta-blockers and NaSSA.

Effective management of akathisia is crucial, with benzodiazepines, beta-blockers, and NaSSA offering evidence-based options. Treatment rankings provide guidance for clinicians. Future research should prioritize larger, more robust studies to address limitations associated with small sample sizes and publication bias. This research enhances our understanding of interventions for akathisia, offering promising options to improve patient quality of life and prevent complications related to non-adherence and mismanagement.

There are no established treatment guidelines for tardive dyskinesia (TD) based on movement severity. The 12-week ARM-TD and AIM-TD studies in TD patients with baseline Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7) ≥6 showed clinically significant improvements in AIMS score with deutetrabenazine versus placebo. Patients who completed these studies were eligible for the open-label extension (OLE) trial. This post-hoc analysis evaluated deutetrabenazine in TD patients with severe movements.

Subgroups were defined by upper quartile of baseline total AIMS score (local rating). Endpoints were: change and percent change from baseline in AIMS score, and percent of patients achieving ≥50% AIMS reduction from baseline.

337 patients were analyzed. The upper quartile of baseline total AIMS score was 14. Subgroups were defined as >14 and ≤14 at baseline, respectively (n=64 vs 273); data are presented at Week 145 (n=40 vs 120). Mean treatment duration was 880.5 and 760.8 days. Mean±SE daily doses were 41.1±1.6mg and 38.9±1.0mg. Mean±SE change from baseline in AIMS score was –11.0±0.8 versus –5.1±0.3; percent change from baseline was –60.1%±3.6% versus –55.9%±3.0%. More patients with AIMS score >14 had ≥50% AIMS reduction (73% vs 65%). Less patients discontinued (38% vs 51%); reasons included withdrawal by subject (16% vs 25%), adverse event (3% vs 11%), and lost to follow-up (6% vs 7%). Withdrawal due to lack of efficacy was uncommon (5% vs 2%).

Patients with baseline total AIMS score >14 had clinically meaningful reductions in AIMS score, suggesting deutetrabenazine has long-term benefit in these patients.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel