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.

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.

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.

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.

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

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

Depression is an important cause of disability in the United States (US). The care experience of major depressive disorder (MDD) is highly variable and has only been documented to a limited degree. This study examines the prevalence incidence and treatment patterns for MDD in the US general population.

In this longitudinal study 2 interview waves were conducted between 2002 and 2015. The initial wave (W1) was carried out with 12,218 individuals from the general population in 8 US states with participants aged 18 years or older. In the second wave (W2) 10,931 of the initial participants agreed to be interviewed again 3 years later; the analyses were carried out for individuals who participated in both interviews (N=10,931). Diagnosis of MDD was confirmed according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria.

The 3-year incidence of MDD was 3.4% (95% CI 3.1%–3.7%). The prevalence of MDD was 5.1% (95% CI 4.7%–5.5%) and 4.2% (95% CI 3.8%–4.6%) in W1 and W2, respectively. The percentages of participants who achieved partial and complete remission were 4.4% (95% CI 4.0%–4.8%) and 3.9% (95% CI 3.5%–4.3%) in W1 compared with 7.9% (95% CI 7.4%–8.4%) and 4.4% (95% CI 4.0%–4.8%) in W2, respectively. The prevalence of MDD was 13.4% and 16.5% in W1 and W2, respectively, when including participants with MDD partial and complete remission episodes. 61.9% of participants with an MDD diagnosis in W1 had at least one associated comorbidity. 41.8% of participants with an MDD diagnosis at W1 still reported significant depressive symptoms at W2. 19.9% of participants in partial remission and 5.5% of participants in complete remission in W1 did not achieve remission in W2. 52.2% and 42.9% of participants with MDD were treated with an antidepressant (AD) in W1 and W2, respectively; selective serotonin reuptake inhibitors (SSRIs) were the most commonly prescribed (34.7% in W1 vs 28.3% in W2). ADs were mainly prescribed by primary care physicians (45.7%) followed by psychiatrists (31.4%), neurologists (2.5%), and other specialties (7.9%). The average duration of treatment was 36.9 (SE 2.4) months. More than one-third of AD users in W1 expressed dissatisfaction with their AD treatment which translated into changes in types of antidepressant in W2.

Depression affects a sizable part of the general population in the US with a prevalence of MDD at 13.4%–16.5%; yet MDD remains largely undertreated as shown by the finding that only about half (52%) of individuals in this study who met the diagnostic criteria for MDD were treated with an antidepressant (SSRI being the most common treatment). In addition, more than a quarter of patients with MDD in this study did not achieve remission after initial treatment underscoring the challenges in successful antidepressant treatment of MDD.

Takeda Pharmaceuticals U.S.A. Inc. and Lundbeck LLC