In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.

Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.

343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.

Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

This analysis assessed the relative efficacy and tolerability of lurasidone versus other atypical antipsychotics in the treatment of pediatricschizophrenia.

A systematic literature review identified 13 randomized-controlled trials for the treatment of pediatric schizophrenia. A Bayesian network meta-analysis compared the efficacy and tolerability of the following atypical antipsychotics: aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, andziprasidone. Patients were 7-17 years old and trial duration ranged from 6-12 weeks. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause treatment discontinuation, and extrapyramidal symptoms. Results from the fixed effect models were reported as mean differences for continuous outcomes and odds ratios for binary outcomes; each with a 95% credible interval.

Lurasidone had significantly greater improvement compared with placebo for PANSS (-7.95 [-11.76, -4.16]) and CGI-S (-0.44 [-0.67, -0.22]), but did not differ from comparators. The differences in weight gain for lurasidone relative to comparators were as follows: clozapine (-3.81kg [-8.03, 0.42]), olanzapine (-3.62kg [-4.84, -2.41]), quetiapine (-2.13kg [-3.20, -1.08]), risperidone (-1.16kg [-2.14, -0.17]), asenapine (-0.98kg [-1.71, -0.24]), paliperidone (-0.85kg [-1.57, -0.14]), aripiprazole (-0.15kg [-0.88, 0.58]), and ziprasidone (0.38kg [-0.49, 1.24]); all were statistically significant except for clozapine, aripiprazole, and ziprasidone. Rates of all-cause discontinuation andextrapyramidal symptoms were similar for lurasidone and comparators, except aripiprazole and paliperidone, which had higher rates of all-cause discontinuation.

In this network meta-analysis of atypical antipsychotics for the treatment of adolescent schizophrenia, lurasidone was associated with similar efficacy, but less weight gain than active comparators.

This study was funded by Sunovion Pharmaceuticals Inc.

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

Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive treatment for many psychiatric illnesses, including treatment-resistant depression (TRD). Ketamine, an NMDA receptor antagonist, is also an effective antidepressant. This retrospective review examined the clinical benefits of combining these two established treatments for patients suffering from TRD in a novel approach coined combination TMS with ketamine (CTK).

A group of 28 adult patients with a primary diagnosis of unipolar (n=18) or bipolar (n=10) depression received three CTK treatments a week at a private neuropsychiatric practice. Patients were given a concurrent treatment of rTMS (1Hz; 40 minutes; 130% of motor threshold) with bio-marker-determined IV ketamine infusions (0.2–4.7 mg/kg; 30 minutes). The TMS coil was positioned on the mid-prefrontal area. Frequency of treatment was dependent on patient responsiveness (10–30 sessions), which was measured as symptom reduction on the Clinical Global Impression (CGI) scale. CGI data was evaluated pre-treatment, post-treatment and at two-year follow-up.

Mean reduction in CGI severity for the patient group following CTK was 4.46 ± 0.54 at a 99% confidence interval and was deemed statistically significant using a paired t-test (a=0.01, t=22.81, p < 0.0001). This significant reduction in CGI severity was sustained for at least 2 years following treatment completion.

Despite years of unsuccessful treatments, all 28 patients in this trial obtained substantial and enduring reductions in their depressive symptoms following CTK therapy. Further research into method optimization and randomized controlled trials are warranted.

Catatonia is not only present in adults; children & adolescents can suffer from catatonia but are often misdiagnosed. A study by Ghaziuddin, Dhossche and Marcotte (2012) found that 18 of the 101 child and adolescent patients had symptoms of catatonia, but only 2 actually had been given a diagnosis by their providers.

17-year-old male who was recently discharged from the inpatient psychiatric unit with the diagnosis of Major Depressive Disorder. His discharge medication was bupropion XL 150mg daily. Within 10 days of his discharge, he was back to the emergency room with worsening anxiety and manic symptoms. At the emergency room, patient’s sister reported that he was acting differently within the last 3–4 days, and making statements that he can save the world that everyone was talking about him. He was also speaking faster than usual, having decreased need for sleep. He reported hearing voices, seeing things. Patient was admitted again, and was given diagnosis of Bipolar Mood Disorder, type I, manic phase, with psychosis. He was started on divalproex 500mg bid for mood stabilization. His Bupropion was discontinued. Gradually his Divalproex was increased to 750mg bid. During his hospital stay he developed lack of spontaneous speech, sluggish responses to questions with automatic answers such as “I don’t know”. He also developed very sluggish motor movements. There was negativism. He needed one on one support for his daily activities of living, needed step by step instructions for all ADLs.

All the test results were negative including EEG, MRI and CT scan of the brain. Bush Francis catatonia rating scale was done and he scored 15. Lorazepam Challenge Test was performed, and the scale was repeated after the patient was given an IM dose of 2mg of Lorazepam, and he scored 2. At this point catatonia diagnosis was confirmed. He was started on scheduled doses of Lorazepam, gradually his Lorazepam dose was increased up to 9mg per day. His catatonia responded to Lorazepam treatment.

17 year old male who initially hospitalized for symptoms of MDD and discharged with antidepressant, came back to the ER within 10 day with symptoms of mania with psychosis. During in-patient’s 2nd in-patient stay he developed catatonia, which was promptly diagnosed and appropriately treated with Lorazepam.

Catatonia can happen in children & adolescents with mood disorders, or with other psychiatric or medical conditions. Timely diagnosis and treatment is very crucial to avoid poor outcome, especially because treatment options for catatonia are well understood; Benzodiazepines, electroconvulsive therapy and reduction or discontinuation of antipsychotics are successful in the treatment of catatonia (Ghaziuddin, Dhossche and Marcotte, 2012).

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

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.

Naloxone use has increased in recent years in response to the nation’s opioid crisis. Once only available to health care professionals, it is now obtainable by prescription for persons at risk for substance overdose and their families. Increasing its availability is seen by some as an “over-the-counter solution” to the opioid problem. However, while naloxone has been viewed as relatively safe, with a low side effect profile when appropriately dosed and monitored, it is not without safety concerns that may go unrecognized or misattributed to other causes.

Here we present a case study of a 41-year-old female who presented to our medication-assisted treatment (MAT) clinic complaining of sudden onset weight gain, shortness of breath, upper and lower extremity peripheral edema, tachycardia, insomnia, and nocturnal enuresis. These symptoms made it difficult for her to work at her housekeeping job, resulting in missed workdays. She had seen a primary care provider for her symptoms and been prescribed a rescue inhaler for her shortness of breath. This patient had previously been treated for opioid use disorder with buprenorphine/naloxone and experienced similar symptoms, which disappeared when she relapsed on opioids. However, symptoms reappeared upon resuming her prescribed treatment.

The patient was identified as experiencing side effects to naloxone, causing noncardiogenic edema. Her MAT medication was switched to buprenorphine. Within two weeks her heart rate had returned to normal, she had lost weight, and she no longer had nocturnal enuresis or needed the rescue inhaler. Her peripheral edema resolved so she was able to walk better and resume work. At the same time, buprenorphine continued to relieve her cravings.

There is a dearth of information related to naloxone-induced edema. Our patient had not received a formal evaluation of pulmonary edema, but her pulmonary and cardiac symptoms were consistent with that diagnosis. Although pulmonary edema is mentioned in the product literature, peripheral edema is not. A literature search indicates that the number of case studies on naloxone-induced pulmonary edema have increased since 2018, but only one other case of naloxone-induced peripheral edema was discovered.

Naloxone is used in a variety of settings by differing types of health care providers. As the number of persons treated with naloxone increases, there will likely be a corresponding increase in incidences of pulmonary and/or peripheral edema as side effects. Providers and patients who are not aware of these manifestations and their relationship to naloxone treatment may easily attribute presenting symptoms to cardiogenic or other causes, as this case illustrates. It is important for providers in all settings to consider new onset shortness of breath and edema within the context of the person’s whole health and to be aware of their implications for mental as well as physical health.

No Funding

Bipolar disorder (BD) is a severe psychiatric disorder associated with structural and functional brain abnormalities, some of which have been found in unaffected relatives as well. In this study, we examined the potential role of decreased fractional anisotropy (FA) as a BD endophenotype, in adolescents at high risk for BD.

We included 15 offspring of patients with BD, 16 pediatric BD patients, and 16 matched controls. Diffusion weighted scans were obtained on a 3T scanner using an echo-planar sequence. Scans were segmented using FreeSurfer.

Our results showed significantly decreased FA in six brain areas of offspring group; left superior temporal gyrus (LSTG; P < .0001), left transverse temporal gyrus (LTTG; P = .002), left banks of the superior temporal sulcus (LBSTS; P = .002), left anterior cingulum (LAC; P = .003), right temporal pole (RTP; P = .004) and left frontal pole (LFP; P = .017). On analysis, LSTG, LAC, and RTP demonstrated a potential to be an endophenotype when comparing all three groups. FA values in three regions, LBSTS, LTTG, and LFP were increased only in controls.

Our findings point at decreased FA as a possible endophenotype for BD, as they were found in children of patients with BD. Most of these areas were previously found to have morphological and functional changes in adult and pediatric BD, and are thought to play important roles in affected domains of functioning. Prospective follow up studies should be performed to detect reliability of decreased FA as an endophenotype and effects of treatment on FA.

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.

Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.

Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.

Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.

No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Pediatric psychiatric inpatients are among the most vulnerable individuals in society. While the use of seclusion and restraint is well chronicled in the field of research in this population, there is limited literature describing the effects, meaning, and attitudes of mandating the wear of clothing in hospital settings. This research explores the phenomenon of the practice of mandatory wear of hospital-issued clothing and its meaning to patients and the awareness and attitudes of this practice among staff caring for this population. This research aims to improve understanding of the experiences of patients regarding this practice at a large, urban hospital providing care for children using a mixed methods design. A qualitative, descriptive phenomenological analysis was conducted through individual interviews with adolescent patients (N = 5) on an inpatient psychiatric unit. Additionally, a cross-sectional self-reported questionnaire examined the awareness and attitudes toward this practice among unit staff (N = 41). The patients’ attitudes toward clothing restrictions was predominantly negative, noting a lack of self-expression, feeling like a mental health patient, desires to wear ones’ personal clothing, and feelings of shame and punishment. Among the staff there was a modest correlation between age, number of years practicing as a health professional, and years practicing in a pediatric setting with feelings of a need for a change in the clothing policy to allow patients to wear their own clothing on admission. Staff age and number of years working at the institution demonstrated a modest correlation between awareness of legal statutes regarding patients’ rights to their own clothing. This research found a readiness among staff to adopt a clothing policy that would permit patients to wear their own clothing on admission, which would improve the negative experiences described among the patients in the sample.

No Funding

Art therapy is a unique and magical psychological treatment method with a particularly significant therapeutic effect on patients with mental illness. Under the pressure of employment and life, many students may experience psychological problems to some extent. And the psychological development of educational teaching methods is the future academic development trend. The research focuses on the music curriculum system, combining it with educational psychology theory to explore teaching paths and teaching courses with drug therapy to assist in treatment.

The study selected 200 college students with borderline disorders and personality split as the subjects and divided them into experimental and control groups. The control group received traditional medication treatment and received routine music education. Based on the control group, the experimental group reformed the music teaching curriculum system to assist in therapy. The treatment cycle is 16 weeks.

The study used the Personality Diagnosis Questionnaire (PDQ-4+) as an evaluation tool and processed the data using SPSS23.0 software. The results showed no statistically significant difference in the baseline PDQ-4+edge subscale scores between the two groups of patients before intervention (P>0.05). After intervention treatment, the marginal symptoms of both groups of patients were improved, and the improvement effect of the experimental group was significantly better than that of the control group (P<0.05).

Considering the path reform of educational psychology in the construction of the music curriculum system and incorporating it into the treatment of students with borderline personality and personality split can effectively alleviate their symptoms.

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.

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.

Treatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.

AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.

To evaluate the effect of AXS-05 in improving anhedonic symptoms in MDD.

GEMINI (N=327) was a randomized, double-blind, placebo-controlled, 6-week study, which randomized adults with MDD to AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) or placebo, twice daily. The primary endpoint was change from baseline in the MADRS total score at Week 6. A post-hoc analysis was conducted to determine the impact of AXS-05 versus placebo on the 5-item MADRS anhedonia subscale (MAS).

Baseline MAS scores were 19.8 and 19.6 in the AXS-05 and placebo group, respectively. At Week 1, AXS-05 treatment resulted in a significant mean reduction from baseline in the MAS score of 4.44 versus 2.69 points for placebo (p< 0.001). At Week 6, the mean reduction from baseline in the MAS was 9.70 for AXS-05 compared to 7.22 for placebo (p=0.001). Response rates (≥ 50% MAS improvement) were significantly greater for AXS-05 compared to placebo at Week 1 (p< 0.001) and at every time point thereafter.

Treatment with AXS-05 was generally safe and well tolerated. The most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.

Treatment with AXS-05 rapidly and significantly reduced anhedonic symptoms as well as overall depressive symptoms.

Axsome Therapeutics