As a result of COVID-19, patients and clinicians rapidly shifted to telehealth. An observational survey study, Real-World Tele-Health Evaluation of Tardive Dyskinesia (TD) Symptoms Communication/Observation Procedure Evaluation in Outpatient Clinical Settings (TeleSCOPE), was conducted to better understand how this shift affected the evaluation of drug-induced movement disorders (DIMDs), including TD.

Twenty-minute online quantitative surveys were conducted with neurology and psychiatry specialists (physicians and advanced practice providers) who met the following criteria: ≥3 years of practice with ≥70% of time spent in a clinic; prescribed a vesicular monoamine transporter 2 (VMAT2) inhibitor or benztropine for DIMD at least once in the past 6 months; and conducted telehealth visits with ≥15% of their patients from December 2020 to January 2021.

Respondents included 277 clinicians (neurology = 109, psychiatry = 168). Telehealth visits increased after COVID-19, with significantly greater increases in psychiatry vs neurology: phone (38% vs 21%); video (49% vs 42%). Across both specialties, top drivers/prompts for further DIMD evaluation were as follows: mention of tics or movements by family members or others (86%); trouble with gait, falls, walking, or standing (82%); difficulty swallowing or eating (74%); and difficulty writing, using phone, computer (71%). However, in the 6 months prior to June 2021, virtual evaluation, diagnosis, and monitoring of patients were challenging. For both specialties, many at-risk patients (ie, taking a dopamine receptor blocking agent) were not evaluated for DIMDs via video-based visits (psychiatry = 45%, neurology = 70%) or phone-only visits (psychiatry = 76%, neurology = 91%). Clinicians listed evaluation of gait/falls/walking/standing as the most challenging aspect of virtual assessment for phone-only visits (psychiatry = 53%, neurology = 57%) and video-based visits (psychiatry = 26%, neurology = 31%). Additional challenges included limited access to computers, insufficient training for clinicians and staff, and greater difficulty obtaining reimbursements (especially for complex telehealth visits). Patients without a participating caregiver, along with lower functioning patients, were at the highest risk of a missed DIMD diagnosis.

During the COVID-19 pandemic, telehealth significantly reduced clinicians’ ability or willingness to evaluate, diagnose, and monitor DIMDs. Clinicians stated multiple factors increased the risk of a missed or incorrect diagnosis. Challenges to optimal telehealth effectiveness included lack of patient access to computers, need for more clinician/staff training, lack of awareness of coverage, need for sufficient fee reimbursement. In-person evaluation continues to be the gold standard for assessing and treating DIMDs. However, if telehealth is necessary, the use of specific questions and directions is recommended for better communication and more accurate assessments.

Neurocrine Biosciences, Inc.

A planned subgroup analysis of a phase 3 study was performed to evaluate the efficacy and safety of pimavanserin (PIM) in Parkinson’s disease psychosis (PDP) patients withglobal cognitive impairment.

PDP is frequent, distressing, a leading cause of institutionalization, complicates PD management and is linked to increased morbidity, incident dementia and mortality. PIM, a selective serotonin receptor (5-HT2A) inverse agonist/antagonist, is newly FDA-approved for the treatment of hallucinations and delusions associated with PDP.

In Study 020, a 6-week FDA registration study, 199 patients with baseline Mini-Mental State Examination (MMSE) score ≥21, moderate-severe psychosis, and on stable PD meds, were randomized to PIM (34 mg/day) or placebo (PBO) for 6 weeks. This subgroup analysis evaluates efficacy and safety between two groups: those with MMSE total score ≥21 but <25 (cognitively impaired; equivalent to Montreal Cognitive Assessment [MoCA] score 15-19) and those with score ≥25 (cognitively normal; equivalent to MoCA score 20-30). Safety assessments were performed on the full safety dataset (i.e., three 6-week placebo-controlled studies) including 614 subjects (PIM=382, PBO=231).

Overall, patients in the PIM group experienced a statistically significant improvement in SAPS-PD scores from baseline to Day 43 compared with PBO (-5.79 vs. -2.73; p=0.001). In the subgroup analysis stratifying by baseline MMSE score, the change from baseline to Day 43 compared with PBO in the cognitively-impaired group (N=50) was numerically larger (-7.11 vs. -0.47; p=0.002). In the full safety dataset examining cognitively impaired patients, there were no between-group (PIM vs. PBO) differences in any treatment-emergent adverse event (TEAE) (57.6% vs. 56.1%) or serious TEAE (6.8% vs. 5.3%). The most common TEAEs occurring at ≥5% in either group were fall (7.4% vs.10.5%), confusional state (6.5% vs.1.8%), and orthostatic hypotension (0.0% vs. 8.8%).

In this subgroup analysis of PDP patients, the treatment effect of PIM on SAPS-PD was larger in the cognitively-impaired group, with similar TEAE and serious TEAE rates. These results hold promise for cognitively-impaired patients that will be further elucidated in future studies.

Clinical study was funded by ACADIA Pharmaceuticals Inc.

There are currently no approved pharmacotherapies to treat cognitive impairment associated with schizophrenia (CIAS). Iclepertin (BI 425809) is a novel glycine transporter-1 inhibitor under development for treatment of CIAS. A previous study demonstrated pro-cognitive effects of iclepertin in patients with schizophrenia; however, concurrent cognitive stimulation could in theory enhance any pro-cognitive pharmacological effects on neuroplasticity. We present preliminary demographics and baseline data from a trial exploring the efficacy of iclepertin together with at-home computerized cognitive training (CCT).

This is an ongoing Phase II, double-blind, placebo-controlled, parallel-group trial in patients with schizophrenia on stable antipsychotic therapy across ~58 centers in 6 countries. Patients aged 18–50 years, compliant with CCT during the run-in period (completing ≥2 hours/week for 2 weeks), were randomized (1:1) to receive once-daily iclepertin 10 mg or placebo together with CCT for 12 weeks. Thereafter, minimum compliance for at-home CCT is 1 hour/week, with a target of ~30 hours across 3–5 sessions totaling 2.5 hours/week. Patients have been stratified to balance potential effects of age (18–40; 41–50 years). Primary endpoint is change from baseline (CfB) in neurocognitive composite T-score of the MATRICS Consensus Cognitive Battery (MCCB) at Week 12. Secondary endpoints include CfB in the Schizophrenia Cognition Rating Scale (SCoRS) total score, MCCB overall composite T-score, and Positive and Negative Syndrome Scale (PANSS) total scores. Novel exploratory endpoints include the Virtual Reality Functional Capacity Assessment Tool to assess daily functioning and the Balloon Effort Task to assess motivation in cognitive performance.

Of the planned sample of 200 randomized patients, the overall treated population currently includes 183: 67% (n=122) are male; mean (standard deviation [SD]) age and time since first diagnosis are 38.2 (7.9) years and 13.5 (8.5) years. Overall, 49% (n=89) are White and 43% (n=79) are Black or African American; 80% (n=147) are from North America, 15% (n=28) from Europe, and 4% (n=8) from Australia/New Zealand. Mean (SD) baseline MCCB neurocognitive composite and overall T-scores (n=178) are 33.7 (11.9) and 32.5 (12.6). Mean (SD) baseline SCoRS total score (n=167) is 35.2 (8.7). Mean (SD) baseline PANSS total and negative symptom scale scores (n=183) are 64.7 (14.6) and 17.3 (5.4). Median (Q1, Q3) CCT compliance over the on-treatment period for patients who have completed or discontinued early is 2.00 (1.21, 2.51) hours/week.

This trial is, to our knowledge, the largest of its kind combining daily pharmacotherapy for CIAS with at-home CCT. It will indicate whether iclepertin together with concurrent cognitive stimulation provides enhanced cognitive benefit, and whether any improvements in neurocognition can translate into improved measures of daily functioning in patients.

Boehringer Ingelheim International GmbH (NCT03859973/1346-0038)

The impact of pandemic events such as the coronavirus (COVID-19) pandemic led to an economic crisis worldwide as well as an increase of mental health problems. In the United States, the gaps in the mental health care system struggle to meet the needs of vulnerable populations and have caused a major public health problem. We aim to increase the awareness of health care professionals, psychiatrists, and policy makers regarding failures and gaps in the mental health care system and suggest new ideas to overcome the growing burden of mental disorders.

We utilized data from PubMed, Science Direct, Cochrane, Embase and Clinicaltrials.gov databases to analyze available information on the US mental health system. We included any relevant articles addressing the prevalence of mental diseases, disparities and the gaps for an accessible and affordable mental health system, as well as the psychological impact of COVID-19 pandemic.

‘COVID-19’, ‘Coronavirus’, ‘SARS-CoV-2’, ‘mental health’, ‘Health, Mental’ were used.

Following scoping review of several studies we noticed that while prevalence of mental health problems in the US varies between states and socio-demographic groups, it is among the top 10 causes of premature death and disability in adults. We noticed that mental health problems are currently one of the costliest public health issues in the healthcare system. Tracking Poll from one of the studies in our scoping review suggested that financial inequities are magnified by the COVID-19 pandemic and that psychological distress was substantially larger among respondents with lower income (33%), Hispanics (28%) and Blacks (26%). Furthermore, in another poll 62% of US population are shown to be anxious due to COVID-19. We observed that the prevalence of reported symptoms of psychological distress among US adults increased when compared to 2018. Common barriers such as failure of accessibility, insufficient funding, insufficient psychiatric beds, limited insurance access and economic burden, clinician shortages, fragmented care, insufficient mental health care policies and insufficient education and awareness about mental illness become more prominent during the COVID-19 pandemic era.

The impact of COVID-19 on mental health is alarming, which affects public health and has made the health care system more vulnerable. Pandemic events not only cause acute negative impact, they also result in long-lasting health problems, isolation and stigma. The COVID-19 pandemic threatens the mental health of the population and its long-term consequences can lead to a secondary pandemic. The outcomes of the COVID-19 pandemic on mental health emphasize the need for policies and strategies to support and strengthen a concerted effort to address its burden on the US mental health care system. In addition, it magnifies the need for high quality and well-funded research for future pandemics.

Opioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.

We obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.

We found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.

Naltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.

Hyponatremia is an electrolyte disorder that can be caused by multiple factors, among which the syndrome of inappropriate antidiuretic hormone secretion (SIAHS) is one of the most frequent causes. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressant drugs in all age groups for efficacy, safety, and adverse effects, although they can cause serious and undesirable side effects.

Report of a series of cases of patients with SIAHS secondary to the use of SSRIs.

We report 21 cases of patients between 52 and 76 years of age, of both sexes, undergoing treatment for depressive disorder with SSRI antidepressants and anxiolytics, concomitant with other clinical treatments (ACEI, thiazides, and carbamazepine). Biochemical laboratory and electrocardiogram studies were performed prior to the start of treatment.

In the first weeks (mean = 2.5) after starting psychopharmacological treatment, hyponatremia (mean = 126 mEq/L) was recorded in 9 symptomatic patients, and Inadequate Antidiuretic Hormone Secretion Syndrome (SIAHS) was diagnosed with referral to Nephrology and Endocrinology. The SSRI was withdrawn, achieving normalization of the biochemical values (plasma and urinary sodium, plasma, and urinary osmolarity), psychotherapy was reinforced until the rotation of another antidepressant. The mean time of suspension of the antidepressant was 7.1 days, the time of disappearance of symptoms after the suspension was 4.3 days and the normalization of biochemical values was 21.68 days. Only one case was severe and 5 required hospitalization.

In the cases presented, the SSRI antidepressants were associated with hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion. This adverse event was more significant in elderly patients and in those treated with other drugs that cause the disease, such as antineoplastic, diuretic, and antiepileptic drugs, due to synergism between the causative mechanisms.

No funding

The dual orexin receptor antagonist lemborexant (LEM) is approved in multiple countries including the United States, Japan, Canada, and Australia for insomnia treatment in adults. In phase 3 study E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), LEM provided significant benefit vs placebo (PBO) on subjective sleep outcomes over 6 months and was well tolerated. This post hoc analysis evaluated the effect of LEM on sleep outcome measures and insomnia severity as assessed by the Insomnia Severity Index (ISI) over 6 months in subjects with a lifetime history of depression (DepHx subgroup). We performed this analysis as insomnia in DepHx subjects could be a residual symptom of unresolved depression, and therefore, these subjects may respond differently to insomnia treatment.

Study 303 was a randomized, double-blind, 12 months global study in adults (≥18 years) with DSM-5 insomnia disorder. For 6 months (Treatment Period 1), subjects were randomized to PBO or LEM (5 mg [LEM5]; 10 mg [LEM10]). For the next 6 months (Treatment Period 2; not reported), PBO subjects were rerandomized to LEM and LEM subjects continued their original dose. The inclusion criteria allowed for participation of subjects with a lifetime DepHx, concomitant antidepressant medication use and/or mild depression (maximum Beck Depression Inventory II score of 19). Subjects had a baseline ISI total score (ISI-ts) ≥15.

The Full Analysis Set comprised 949 subjects, including 112 subjects in the DepHx subgroup (PBO, n = 34; LEM5, n = 39; LEM10, n = 39). Baseline median subjective sleep onset latency (sSOL; minutes) was 52.9, 57.1, and 70.7 for PBO, LEM5, and LEM10, respectively. At 6 months, greater median decreases from baseline in sSOL were observed with LEM5 (−21.7) and LEM10 (−40.1) vs PBO (−12.9). Baseline mean subjective sleep efficiency (sSE; %) was 62.2, 59.2, and 62.4 for PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) increases from baseline in sSE were observed with LEM5 (17.2 [18.3]) and LEM10 (20.9 [19.0]) vs PBO (14.9 [15.4]). Baseline mean subjective wake after sleep onset (sWASO; minutes) was 123.7, 151.0, and 132.6 for PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) decreases from baseline in sWASO were observed with LEM5 (−52.7 [69.2]) and LEM10 (−68.8 [81.9]) vs PBO (−46.7 [69.4]). Mean baseline ISI-ts were 18.6, 19.9, and 19.0 PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) decreases from baseline in ISI-ts were observed with LEM5 (−9.1 [6.8]) and LEM10 (−10.0 [5.9]) vs PBO (−7.9 [5.6]). Treatment-emergent adverse event rates in the DepHx subgroup were similar to those in the overall study population.

At 6 months, LEM improved patient-reported sleep outcomes and reduced patient-reported insomnia severity in subjects with DepHx. These results suggest that LEM may be a therapeutic option for patients with insomnia and DepHx.

Eisai, Inc.

Few studies have analyzed compulsive buying behavior in relation to a specific product. Smartphones are hugely popular products today, especially among young people. These two aspects have motivated this research into the compulsive buying behavior of Smartphones by university students.

To study this behavior, the main features that differentiate compulsive buyers from those that are not are analyzed, and their risk profiles are obtained through a discrete choice model.

Sociodemographic features that define buyers with the greatest propensity to compulsiveness are younger age, longer time spent daily using social networks, higher spending on the acquisition of Smartphones and having owned a greater number of these devices. These buyers also show shopping addiction and greater feelings of guilt after the purchase as well as more positive and negative affective states when purchasing Smartphones.

This analysis not only determines the characteristics that define young individuals with a tendency toward compulsiveness in Smartphone purchases, but also contributes to quantifying the probability of having this tendency.

The fast pace of modern life and work competition has led to an increase in the incidence rate of depression year by year. In recent years, Mongolian medicine has achieved good results in the treatment of depression. Research on the production of Mongolian medicine group based on Qiwei Guangzao pill to explore its therapeutic effect on moderate depression.

The study selected 70 patients with moderate depression and randomly divided them into an experimental group and a control group. The experimental group received Mongolian medicine based on Qiwei Guangzao pills in the morning, middle, and evening, supplemented by droperidol and melitracen tablets; The control group only received oral administration of flupentixol and melitracin tablets. The treatment course was 4 weeks, and the patient’s status was evaluated by Hamilton Depression Scale (HAMD) score. SPSS25.0 software was used for statistical analysis of the data obtained.

Compared to the control group, the rehabilitation rate of patients in the experimental group was 14.3%, and the proportion of patients with significant treatment effects was 45.8%. The total effective rate was about 91.4%, indicating that the improvement of HAMD scores in the experimental group was higher than that in the control group.

The experimental results show that the Mongolian medicine group based on Qiwei Guangzao pill has a significant therapeutic effect on moderate depression, and can effectively improve patients’ sleep status and gastrointestinal symptoms.

The National Natural Science Foundation of China, Correlational study on Lianqiao-4 and intestinal flora in the treatment of liver injury by the theory of “ essence and dross decomposition” (Grant No. 82060910); The National Natural Science Foundation for Young Scientists of China, Study on genomics and proteomics mechanism of Lianqiao-4 against liver injury based on the theory of “ essence and dross decomposition “ in Mongolian Medicine (Grant No. 81760765); The central government supported cross-disciplinary projects with special funds for local construction (No. JCHXKXM001).

A combination of olanzapine and samidorphan (OLZ/SAM) is in development for schizophrenia to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The objective of this phase 1 exploratory study was to assess metabolic treatment effects of OLZ/SAM.

Healthy, non-obese adults (18–40 years) were randomized 2:2:1 to once-daily OLZ/SAM, olanzapine, or placebo for 21 days. Assessments included oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, weight gain, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance.

Sixty subjects were randomized (OLZ/SAM, n=24; olanzapine, n=24; placebo, n=12); 19 (79.2%), 22 (91.7%), and 11 (91.7%), respectively, completed the study. In the OGTT, olanzapine led to significant hyperinsulinemia (P<0.0001) and significantly reduced insulin sensitivity (2-hour Matsuda index) at day 19 vs baseline (P=0.0012), changes not observed with OLZ/SAM. No significant between-group differences were observed for change from baseline in clamp-derived insulin sensitivity index at day 21. Least squares mean weight change from baseline was similar with OLZ/SAM (3.16 kg) and olanzapine (2.87 kg); both were significantly higher than placebo (0.57 kg; both P<0.01). Caloric intake significantly decreased from baseline to day 22 with OLZ/SAM (P=0.015) but not with olanzapine or placebo. Forty-nine subjects (81.7%) experienced ≥1 AE (OLZ/SAM, 87.5%; olanzapine, 79.2%; placebo, 75.0%).

In this exploratory study, hyperinsulinemia and decreased insulin sensitivity were observed in the OGTT with olanzapine but not with OLZ/SAM or placebo. Clamp-derived insulin sensitivity index and weight changes were similar with OLZ/SAM and olanzapine in healthy subjects during the 3-week study.

This study was funded by Alkermes, Inc.