Flibanserin, a serotonin antagonist currently indicated for treatment of female sexual dysfunction disorder, has not heretofore been described to worsen cerebellar function. Such a case is presented.

A 60-year-old woman, 8 months prior to presentation, had an acute onset of fainting and hitting her head into a wall without loss of consciousness. She could not stand up, had left-sided weakness, and vomiting, with garbled, slow speech and severe headache. Findings in the emergency room showed a left cerebellar parenchymal hemorrhage of 3.2 x 3.1 x 2 cm with the epicenter at the dentate nucleus, extending medially towards midline into the cerebellar vermis, with surrounding perilesional edema extending into the middle cerebellar peduncle. Also, 5.2 cm of the hemorrhage extended from the petrous of the tentorium to the cerebellar vermis. Moreover, a ventral left thalamic hemorrhage with subependymal clot at the foramen of Monroe extended into the dependent portion of lateral ventricles without midline shift. Post one month of physical therapy, speech, walking, and coordination improved but she continued to have delayed speech and trouble getting up, with a wide stance.

Neurologic Examination: Cranial Nerve (CN) Examination: CN XI: Sternocleidomastoid hypertrophy, horizontal titubation. Motor examination: Drift test: L pronator drift with L abductor digiti mini sign. Gait examination: heel walking, dystonic posture of L hand. Tandem gait: unstable, wide based. Cerebellar examination: Both (B) finger-to-nose dysmetria, Left > Right. Slow rapid alternating movements (RAM) L Upper Extremity (UE). Due to absent sexual desire she started 100 mg of flibanserin nightly. Maintaining this for 5 weeks, her coordination markedly worsened with poor balance and a need for a cane to ambulate. She would stumble, with a wider gait, and found climbing stairs challenging. Physical examination displayed worse cerebellar function: prominent horizontal titubation. Finger-to-nose—dysmetria L>R. Decreased RAM, L UE. Markedly positive Holmes Rebound phenomenon, Bilateral UE. Tandem gait: unstable. A week post stopping flibanserin, gait and cerebellar examination returned to baseline.

The temporal correlation between the use of flibanserin and transient worsening of cerebellar function strongly suggests that this is the causative agent. Since serotonin is essential in cerebellar function, including its action on the cerebellar cortex and deep cerebellar nuclei, it strongly suggests that its action as a serotonin antagonist is the mechanism whereby flibanserin is causing cerebellar symptoms. In those on flibanserin, investigation to detect the presence of cerebellar dysfunction is warranted. Assessment for the presence of cerebellar dysfunction in those who are on anti-serotonin drugs, such as cyproheptadine and methysergide, may be worthwhile.

No Funding

Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).

Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.

Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.

These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.

Myriad Neuroscience/Assurex Health

Restraint and seclusion were considered a form of treatment but consistently has led to physical and mental injuries to staff and patients. De-escalation has been viewed as a safer option. Understanding which intervention yields decreased injuries, aggression and violence will guide policy and inform practice.

To identify which intervention leads to decreased physical and psychological injury to patients and staff.

The frequency of physical injuries to patients and staff from aggressive patients; frequency of psychological injuries to patients and staff from violent, aggressive incidents; frequency of violence, agitation and aggression; competence of staff at managing aggression and violence were evaluated.

Fourteen studies were included in this review. There are many forms of de-escalation. Studies where techniques were taught to staff, the intervention was effective in decreasing injury in approximately half the studies. De-escalation techniques taught to patients decreased injury in 100% of the studies included in this review.

Consensus on which intervention works best could not be reached, nor is there overwhelming evidence for a particular type of de-escalation better suited for decreasing aggression and violence. Caution should be exercised when choosing a de-escalation technique for implementation in institutions due to lack of regulating agencies that inform practice and standards. In addition, the literature lacks best practices for de-escalation techniques backed by evidence. Restraint and seclusion should be used as a last resort due to inherent risk associated with the intervention.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung disease, and its condition can lead to depressive disorders in patients. Understanding the subjective sleep quality of ARDS patients with depressive disorder conditions and their influencing factors is essential for developing effective interventions and improving patients’ sleep quality.

Sixty patients with depression were selected as the study subjects and randomly divided into experimental and control groups, with 30 people in each group. Pittsburgh Sleep Quality Index (PSQI), Symptom Checklist-90 (SCL-90), Self-Rating Anxiety Scale (SAS), Social Desirability Scale (SDS), State-Trait Anxiety Inventory (STAI), Life Event Scale (LES), and SQL Server Reporting Services (SSRS) were used for assessment. The data collected were analyzed by the relationship between PSQI and the results of the other six rating scales using SPSS23.0.

Sleep disorders were found in 77.8% of 60 patients with depression. The total score and factors of PSQI were significantly correlated with SCL-90 somatization, obsessive-compulsive disorder, depression, anxiety, and total mean score (P<0.05). The PSQI was positively correlated with SAI in SAS and STAI (P<0.01) but not correlated with TAI in STAI (P>0.05). The somatization disorder factor in SDS was significantly correlated with the PSQI factors and total scores except for the sleep persistence factor (P<0.05). The daytime dysfunction factor in PSQI was significantly correlated with the full score of social support (P<0.05), whereas there was no significant correlation between PSQI and LES (P>0.05).

Depressive disorders in ARDS patients hurt their subjective sleep quality.

The teaching support work of normal school students is a key step to improving students’ personal teaching abilities. It can help students understand the current situation of education in China and is a necessary way to enhance students’ sense of responsibility and mission in teaching. However, a large number of students will have significant mental symptoms such as depression and anxiety during teaching. Therefore, doing a good job in students’ mental health is not only conducive to teachers’ psychological construction, but also can promote students to develop a good outlook on education.

118 voluntary students in a university were taken as the research objects, and all the students were divided into an experimental group and a control group, with 59 students in each group. The intervention means based on the transformation of the management mode of psychotherapy combined with education were proposed. The students in the experimental group used the combined treatment means, while the students in the control group only used psychotherapy for intervention. The intervention lasted for 12 months, and the changes in anxiety and depression symptoms of students during the intervention were evaluated.

The differences in anxiety and depression scores of students before and after the treatment are shown in Table 1.Table 1.

Changes in scores of psychological depression and anxiety in two groups of students

The psychological condition of the students is the key to deciding whether their voluntary activities can be carried out normally. It can be seen from Table 1 that the depression and anxiety scores of students in the experimental group are significantly lower than those in the control group after the intervention. Therefore, it can be seen that the transformation of the management mode of psychotherapy combined with education can significantly reduce the current situation of psychological depression and anxiety of students in the support education, which is of great significance to the comprehensive development of students.

The research is supported by: The key commissioned project of Higher Education Teaching Reform of Heilongjiang Province in 2021: “The Research on the Effective Connecting Mode and the Implementation Path of Local Application-Oriented Universities’ Assistance in Poverty Alleviation and Rural Revitalization in Border Underdeveloped Areas” (the Fund Number: SJGZ20210047); The key project of Education Science Planning of Heilongjiang Province in 2021: The Research on the “Cross-border Integration” Talent Training Path of Specialty Groups of Tourism, Trade, Economy and Management of Special Application-oriented Undergraduate Demonstration Universities to Russia (the Fund Number: GJB1421625).

Tardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo.

Patients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55 years) and older (≥55 years) patients.

This analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE): total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were –6.7±0.62 and –6.5±0.47, respectively (percent changes of –61.4%±4.10% and –54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively.

Deutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel

Mindfulness training helps employees better cope with work and life stress by enhancing individual attention and self-awareness. At the same time, mindfulness training can help employees accept and tolerate their emotions and experiences, improve their self-efficacy and self-acceptance ability, and thus reduce anxiety.

A survey was conducted on 20 employees of a listed company in a specific city, and 20 questionnaires were collected, including 13 males and seven females. There were 6 cases with obvious anxiety symptoms, ten subjects with mild anxiety, and four without anxiety symptoms. Sixteen employees with anxiety symptoms were selected as the experimental group and received psychological intervention treatment using mindfulness training. Three months later, they were re-evaluated using the Anxiety Self Rating Scale. The effectiveness of the intervention treatment was statistically analyzed using SPSS23.0 software.

After treatment, the experimental group of employees showed significant improvement in anxiety levels, with six recovered, eight significantly improved, and two not recovered. There was a statistically significant difference between the control and patient groups, with P values less than 0.05.

The overall education level of the company’s employees is relatively high, accompanied by work pressure, interpersonal relationships, and family relationships, leading to anxiety symptoms among employees. Mindfulness training can improve employees’ emotional regulation and coping abilities and promote positive emotions and psychological states.

Social Science Foundation of Hebei Province (No.HB22GL037); New Liberal Arts Research and Reform Practice Project of the Ministry of Education (No.2021120010); National Natural Science Foundation of China (No.71862013).

In VIVRE (NCT04448431), vortioxetine was associated with significantly higher rates of symptomatic and functional remission, better daily and social functioning, and greater treatment satisfaction than desvenlafaxine in patients with major depressive disorder (MDD) and partial response to selective serotonin reuptake inhibitor (SSRI) therapy. This analysis further explored the relative improvement in patient functioning with vortioxetine versus desvenlafaxine.

VIVRE was a randomized, double-blind study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in adults with MDD and partial response to initial SSRI monotherapy. Mean percentage changes from baseline to week 8 in Functioning Assessment Short Test (FAST) total and domain scores were analyzed by treatment group in the overall population and in working patients.

In the overall population, the mean reduction in FAST total score from baseline after 8 weeks of treatment was 37.2% in vortioxetine-treated patients versus 31.8% in desvenlafaxine-treated patients (P = 0.04). Significantly greater improvements versus desvenlafaxine were seen in vortioxetine-treated patients for FAST autonomy, cognitive functioning, and interpersonal-relationships scores (all P < 0.05). In working patients, the mean reduction in FAST total score from baseline at week 8 was 38.7% versus 32.1% in the vortioxetine and desvenlafaxine groups, respectively (P = 0.04). Significant correlations were seen between absolute changes in patient functioning, and those in depression severity and health-related quality of life.

Vortioxetine was significantly better than desvenlafaxine in improving overall functioning as well as daily, social, and cognitive functioning in patients with MDD with inadequate response to prior SSRI therapy.

Legal scholars have psychological problems because they have been in an “abnormal environment” for a long time. Music therapy is a psychological intervention method based on musicology, medicine and psychology. Therefore, the study used music therapy to intervene and treat the psychological diseases of legal scholars.

In the study, 84 patients with psychological diseases in a hospital in a western city were randomly divided into group A (41) and group B (43) by using SPSS21.0 statistical software. Group A was the control group without intervention; Group B was the music group, which was intervened by music therapy. In the experiment, Pittsburgh Sleep Quality Index (PSQI) was used to quantitatively evaluate the sleep quality of patients. The experimental results are shown in Table 1.Table 1.

Sleep quality of patients in the two groups before and after the intervention

Before the intervention, the sleep quality score of group B was significantly higher than that of group A, 2.62 ± 0.57 points; After the intervention, the indexes of group B were lower than those of group A, with a total score of 8.44 ± 2.01, much lower than 10.28 ± 2.14 in group A. The experimental results show that music therapy can significantly improve the psychological diseases of legal scholars.

Legal scholars often suffer from psychological diseases due to long-term “abnormal environment”. The study used music therapy as an adjunctive treatment, and the results showed that music therapy could effectively alleviate mental and psychological diseases.

In a phase 3 trial of children with ADHD, DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, improved ADHD symptoms and reduced at-home early morning and late afternoon/evening functional impairments versus placebo, as measured by the validated Parent Rating of Evening andMorning Behaviors-Revised, Morning (PREMB-R AM) and Evening (PREMB-R PM) subscales. This post hoc analysis evaluated the effect of DR/ER-MPH versus placebo onindividual PREMB-R AM/PM item scores.

Data were analyzed from a pivotal, randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) withADHD (NCT02520388). Using the 3-item PREMB-R AM and 8-item PREMB-R PM, both key secondary endpoints, investigators evaluated early morning and lateafternoon/evening functional impairment by scoring each item on a severity scale from 0 (none) to 3 (a lot). For post hoc analyses, treatment comparisons between DR/ER-MPH and placebo at endpoint were determined by using least squares mean changes from baseline on individual PREMB-R AM/PM items score derived from an analysis ofcovariance (ANCOVA) model with treatment as the main effect, and study center and baseline score as covariates.

Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose achieved after 3 weeks of treatment was 68.1 mg. Following 3 weeks of treatment, DR/ER-MPH significantly reduced mean individual item scores from baseline versus placebo on all PREMB-R AM items (all P≤0.002; “getting out of bed”, “getting ready”, and “arguing or struggling in the morning”). Additionally, DR/ER-MPH significantly reduced mean individual item scores from baseline on 5 out of 8 PREMB-R PM items (P<0.01 in 2 items [“sitting through dinner” and “playing quietly”] and P<0.05 in 3 items [“inattentive/distractible”, “transitioning between activities”, and “settling down/getting ready for bed”]). There was a trend towards a reduction on 2 other items of the PREMB-R PM (P<0.09). Distributions of the ratings for each item will be presented. No serious TEAEs were reported; TEAEs were consistent withmethylphenidate.

Post hoc analyses revealed that DR/ER-MPH significantly reduced all PREMB-R AM item scores, including “getting out of bed”, and many PREMB-R PM items, including “getting ready for bed” in children with ADHD. These findings are worth further exploration.

Ironshore Pharmaceuticals & Development, Inc.

Asenapine is a 2nd-generation antipsychotic currently marketed as a sublingual (SL) tablet in the US for the treatment of schizophrenia. HP-3070, asenapine transdermal system, is a patch for treatment of schizophrenia in adults. Low- and high- HP-3070 doses deliver asenapine concentrations that are similar to SL asenapine 5 mg BID and 10 mg BID, respectively, but with fewer peak and trough fluctuations.

In this Phase 3, randomized, double-blind, placebo (PBO)-controlled, 6-week inpatient study, adults with schizophrenia having baseline Positive and Negative Syndrome Scale (PANSS) total score ≥80 and Clinical Global Impression–Severity of Illness Scale (CGI-S) score ≥4 were randomized 1:1:1 to HP 3070 high-dose, HP-3070 low-dose, or PBO.

The primary efficacy objective was Week 6 PANSS score change from baseline (CFB) vs PBO.

The key secondary objective was Week 6 CGI-S CFB vs PBO. Safety assessments included treatment-emergent adverse events (TEAEs), laboratory results, vital signs, dermal safety, and extrapyramidal symptoms (EPS) assessments.

A total of 616 patients were randomized, with 486 patients completing the study. Discontinuation rates were 23.3%, 18.6%, and 21.4% for HP-3070 high-dose, HP-3070 low-dose, and PBO, respectively; withdrawal of consent and AEs were the most common reasons for discontinuation. Demographics and baseline characteristics were well-balanced among treatment groups.

For PANSS total score, least squares mean (LSM) (standard error [SE]) estimates of the treatment comparison (HP-3070 vs PBO) for CFB at Week 6 were -4.8 (1.634; 95% CI: -8.06, -1.64; p=0.003) and -6.6 (1.630; 95% CI: 9.81, 3.40; p<0.001) for HP-3070 high- and low-dose, respectively. For CGI-S CFB at Week 6, LSM (SE) for the treatment comparison were 0.4 (0.100; 95% CI: 0.55, 0.16; p<0.001) for HP 3070 high-dose and 0.4 (0.099; 95% CI: 0.64, 0.25; p<0.001) for low-dose.

No deaths or serious TEAEs related to study treatment occurred. The HP-3070 safety profile was consistent with SL asenapine. Incidence of TEAEs at the patch application site was higher for HP-3070 (14.2% high-dose, 15.2% low-dose) than for PBO (4.4%); most of these events were mild or moderate in severity. PBO patients had higher rates of psychiatric disorders (24.3% vs 15.7% and 17.6% for HP-3070 high- and low-dose, respectively), with insomnia and anxiety as most common. Study treatment discontinuations due to application site reactions or skin disorders were low (≤0.5%) across treatment groups. There was no marked mean CFB for vital signs or electrocardiogram parameters, nor treatment differences observed on EPS assessments.

In this study, HP-3070 was efficacious, safe, and well-tolerated for treating schizophrenia in adults; both doses met primary and key secondary endpoints. As the first transdermal antipsychotic patch in the US, HP-3070 will provide patients a novel treatment option.

Funded by Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical Co.

The COVID-19 pandemic impacted mental health across different groups, including healthcare workers (HWs). To date, few studies focused on potential positive aspects that may follow the exposure to the pandemic. We investigated the prevalence of posttraumatic stress disorder (PTSD) in Italian HWs and whether posttraumatic growth (PTG) dimensions affected the risk of suicidal ideation (SI) during the first COVID-19 wave.

An online self-report survey was conducted between April and May 2020. Sociodemographic data, information about COVID-19-related stressful events, Impact of the Event Scale-revised, and Post-Traumatic Growth Inventory-Short Form (PTGI-SF) scores were collected and compared between participants. Patient Health Questionnaire-9 scores were also collected to assess SI through item 9. Multivariate logistic regression was used to assess the relationship between PTGI and SI.

Among 948 HWs, 257 (27.0%) reported a provisional PTSD diagnosis. The median PTGI-SF score was 24. Participants reporting PTSD symptoms had higher scores in the Spiritual change, Appreciation of life, and New possibilities domains, and in the total PTG scale. A total of 100 HWs (10.8%) screened positive for SI. Improvements in Relating to others domain of PTGI-SF (odds ratioOR: .46; 95% confidence interval: .25–.85) were associated with lower odds of SI.

COVID-19 pandemic has been indicated as a risk factor for SI, also among HWs. PTG may have a protective role on suicide risk. Improvements in Relating to others domain reduced odds of SI, consistently with the role of loneliness and lack of connectedness with others in enhancing suicidal risk.

MIND-TD is a collaboration of healthcare professionals (HCPs) who are committed to raising awareness of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. The MIND-TD questionnaire was developed to help HCPs screen for TD and facilitate discussion with patients.

In August 2020, an expert panel of 13 HCPs (4 psychiatrists, 6 neurologists/movement disorder specialists [MDSs], and 3 advanced practice providers [APPs]) met virtually to discuss potential screening questions for TD. This work was continued by 4 panelists (1 psychiatrist, 2 neurologists/MDSs, and 1 APP) who tested the questions in clinical practice for revision and refinement. The same group also worked with the sponsor to develop 2 additional sections that could be used to elicit more information from patients. The panel recognized the need for a tool that could facilitate telehealth screening for TD, including audio-only interactions. Therefore, practices from speech-language pathologists (eg, diadochokinetics) were used to refine the questionnaire.

Part 1 of the MIND-TD questionnaire includes a yes-or-no question for each of the 4 following topics: presence of extra or unwanted movements (Movement); feelings of embarrassment or self-consciousness (Impact); if anyone else has noticed the movements (Notice); and if movements interfere with everyday routines (Daily Activities). Part 1 can be administered by any trained medical staff, either in person or via telehealth (with video or audio-only). Routine administration is suggested in all patients who meet any of the following criteria: current or prior use of any first- or second-generation antipsychotic; use of an anticholinergic medication in conjunction with a current or past antipsychotic; or current diagnosis of TD. Part 2 of the MIND-TD questionnaire has 2 sections. The first (Thorough Interview) includes 9 items related to physical/functional difficulties (eg, eating, speaking, walking, and gripping objects) and 3 simple instructions for speech difficulties. The second section (Differentiate) includes checklists of characteristic movements for TD and drug-induced parkinsonism, along with an item related to akathisia and suggestions for observing abnormal or involuntary movements. Part 2 should be administered by the treating HCP in patients who have abnormal movements that may be related to TD. Part 2 requires visual observation of the patient, whether in-person or via video.

MIND-TD is a screening questionnaire that can facilitate a dialogue between HCPs and patients about the risks, symptoms, and impact of TD. The MIND questions can stand alone and be administered during in-person visits or telehealth visits (video or audio-only). The TD section can be used to gather more information about a patient’s abnormal movements.

Neurocrine Biosciences, Inc.