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).

Ketamine, an N-methyl-d-aspartate receptor antagonist, has been “repurposed” as a rapid-acting antidepressant for treatment-resistant depression (TRD). The s-enantiomer of ketamine, “esketamine,” was FDA approved for TRD and depressive symptoms in adults with major depressive disorder with suicidal ideations/behaviors. Intravenous (IV) ketamine, although financially less expensive, is often not covered by insurance and intranasal (IN) esketamine, although covered by insurance can be expensive. There is a paucity of literature on efficacy data comparing subanesthetic IV ketamine and IN esketamine for TRD in a real-world scenario. Thus, we conducted this study comparing the efficacy and the number of treatments required to achieve remission/response with repeated use of subanesthetic IV ketamine/IN esketamine among TRD patients.

This was an observational study where we included adults (≥18 years) with TRD who provided consent and had received up to 6 IV ketamine infusions (0.5 mg/kg, infused over 40 minutes) or up to 8 intranasal (IN) esketamine (56/84 mg) treatments for TRD at the Mayo Clinic Depression Center. Depression symptoms were measured utilizing the self-report 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale before and 24 hours after ketamine/esketamine treatment. Remission and response were defined as QIDS-SR 16 score ≤5 and ≥50% change in QIDS-SR 16, respectively. Continuous variables are reported as means ± SD and categorical variables as counts and percentages. The Wilcoxon rank-sum test was used to compare continuous variables. Chi-square and Fisher’s exact tests were used to compare categorical variables. The number of treatments to remission/response was calculated.

Sixty-three adults with TRD, middle-aged (47.0 ± 12.1 years), predominantly female (65%), of which 76% (n = 48) and 24% (n = 15) received IV ketamine and IN esketamine, respectively. Mean (SE) change in QIDS-SR 16 score was −8.7 ± 0.7 (P < .001), a significant reduction (improvement) from baseline (mean ± SD = 17.6 ± 3.7). Overall remission and response rates were 36.5% and 55.6%, respectively in the acute phase. Response (56.3% vs 53.3%) and remission rates (39.6% vs 26.7%) were similar among patients who received IV ketamine or IN esketamine, respectively (P > .05). The mean number of treatments received to achieve response (2.5 ± 1.6 vs 4.6 ± 2.1) and remission (2.4 ± 1.3 vs 6.3 ± 2.4) were significantly lower among patients who received IV ketamine compared to IN esketamine (P < .005). Most patients tolerated both treatments well.

Intravenous ketamine and intranasal esketamine showed similar response/remission in TRD patients but the number of treatments required to achieve response/remission was significantly lower with IV ketamine compared to IN esketamine. These findings need to be investigated in a randomized control trial comparing these two treatment interventions.

No funding

Wearable sensors have become increasingly accurate in measuring various aspects of health monitoring in humans. Persons with dementia (PWD) often experience problematic behavioral and psychological symptoms of dementia (BPSD). These behaviors can include kicking, hitting, biting, screaming, pushing and are stressful and dangerous for the PWD as well as for caregivers both formal paid caregivers and informal family caregivers. There are many proven methods to intervene during agitated behavior outburst and the earlier these methods are used the better the results. Such methods include redirection, one-on-one socialization, music therapy, pet assisted therapy, etc. These types of effective methods are preferred over routine or as needed medications to control the behaviors. The medications currently used have well documented adverse side effects, especially in aging adults.

This IRB approved study used a convenience sample of eight PWD who had a history of BPSD in an assisted living facility specializing in the care of PWD. We evaluated the use of off-the-shelf smart watch technology to measure limb movements, vocalizations, heart rate and location in a facility. The research goal was to determine the feasibility of using this technology to accurately measure patient data which in turn will allow clinicians to promptly detect agitation and provide early intervention. Output data from the watch was compared to data recorded by trained observers using the Cohen-Mansfield Agitation Inventory (CMAI). Data was collected in four-hour blocks of time over a two-day period.

All the participants wore the devices without difficulty. Observations were then compared to the information obtained from the smart watch technology. Limb movements and heart rate increases correlated well with observers’ measurements of agitation. True positive measures were greater than 60% (data streams from devices correlated with observations). The voice measures of tone, volume and words used did not correlate well due to background noise in this communal environment.

Data streams did correlate with observations. This technology could be useful in quickly identifying, and potentially anticipate, agitation in PWD. Further research is pending that will fine tune our software developed to measure the data streams and enhance accuracy. Also, improvements are being made in the ability to use voice recognition technology to capture the vocalizations associated with agitation. This technology can be used to quickly identify and prevent escalation of some BPSD by allowing early application of non-pharmacologic methods to treat agitation. Further study will also evaluate the impact this may have on the quality of life for caregivers and PWD.

Funding Acknowledgements: Old Dominion University Office of Research, $2,500

Tardive dyskinesia (TD) is typically caused by exposure to antipsychotics, is often irreversible, and can be debilitating. TD symptoms can increase the social stigma of patients with comorbid psychiatric disorders, negatively impact quality of life, and potentially increase medical morbidity and mortality. An increased risk of developing TD has been associated with factors such as older age, female sex, underlying mental illness, and long-term use and higher doses of antipsychotics. The association of TD with the use of typical versus atypical antipsychotics has also been evaluated, with mixed results. To date, predictive models assessing the joint effect of clinical characteristics on TD risk have not been developed and validated in the US population.

To develop a prediction model to identify patient and treatment characteristics associated with the occurrence of TD among patients with psychiatric disorders taking antipsychotic medications, using a retrospective database analysis.

Adult patients with schizophrenia, major depressive disorder, or bipolar disorder who were taking oral antipsychotics, and who had 6months of data prior to the index date were identified from Medicaid claims from six US states. The index date was defined as the date of the first claim for an antipsychotic drug after a claim for the underlying disorder but before TD diagnosis. A multivariate Cox prediction model was developed using a cross-validated version of the least absolute shrinkage and selection operator (LASSO) regression method to improve prediction accuracy and interpretability of the model. The predictive performance was assessed in a separate validation set via model discrimination (concordance) and calibration.

A total of 189,415 patients were identified: 66,723 with bipolar disorder, 68,573 with depressive disorder, and 54,119 with schizophrenia. The selected prediction model had a clinically meaningful concordance of 70% and was well calibrated (P=0.46 for Hosmer–Leme show goodness-of-fit test). Patient’s age at index date (hazard ratio [HR]: 1.03), diagnosis of schizophrenia (HR: 1.73), dosage of antipsychotic at index date (up to 100mg/day chlorpromazine equivalent; HR: 1.40), and presence of bipolar and related disorders (HR: 1.16) were significantly associated with an increased risk of TD diagnosis. Use of atypical antipsychotics at index date was associated with a modest reduction in the risk of TD (HR=0.94).

This study identified a group of factors associated with the development of TD among patients with psychiatric disorders treated with antipsychotics. This may allow physicians to better monitor their patients receiving antipsychotics, allowing for the prompt identification and treatment of TD to help maintain quality of life.

Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA

Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

ALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.

To assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.

This was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).

Of 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.

Treatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.

Funding Acknowledgements: This study was funded by Alkermes, Inc.

Clozapine is an atypical antipsychotic approved by the Food and Drug Administration for treatment-resistant schizophrenia and also indicated for the reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. The most serious side effect of clozapine treatment is agranulocytosis, which is defined as an absolute neutrophil count (ANC) < 0.50 × 109 per L. Benign ethnic neutropenia (BEN) is a condition found in members of African or Middle Eastern descent that is characterized by ANC < 1.50 × 109 per L in the absence of other causes. Filgrastim is a granulocyte colony-stimulating factor (G-CSF) that has shown efficacy in reducing the duration of agranulocytosis in some patients who develop clozapine-induced agranulocytosis. It is currently unknown whether filgrastim is beneficial in the treatment of neutropenia due to BEN. We here, for first the time report a case of a patient with BEN who developed agranulocytosis both during the first clozapine trial for schizophrenia and during the rechallenge, despite early stabilization with filgrastim treatment, which highlights the failure of filgrastim in treating BEN.

No funding.

“Subsyndromal” obsessive-compulsive disorder symptoms (OCDSs) are common and cause impaired psychosocial functioning. OCDSs are better captured by dimensional models of psychopathology, as opposed to categorical diagnoses. However, such dimensional approaches require a deep understanding of the underlying neurocognitive drivers and impulsive and compulsive traits (ie, neurocognitive phenotypes) across symptoms. This study investigated inhibitory control and self-monitoring across impulsivity, compulsivity, and their interaction in individuals (n = 40) experiencing mild–moderate OCDSs.

EEG recording concurrent with the stop-signal task was used to elicit event-related potentials (ERPs) indexing inhibitory control (ie, N2 and P3) and self-monitoring (ie, error-related negativity and correct-related negativity (CRN): negativity following erroneous or correct responses, respectively).

During unsuccessful stopping, individuals high in both impulsivity and compulsivity displayed enhanced N2 amplitude, indicative of conflict between the urge to respond and need to stop (F(3, 33) = 1.48, P < .05, 95% Cl [−0.01, 0.001]). Individuals high in compulsivity and low in impulsivity showed reduced P3 amplitude, consistent with impairments in monitoring failed inhibitory control (F(3, 24) = 2.033, P < .05, 95% CI [−0.002, 0.045]). Following successful stopping, high compulsivity (independent of impulsivity) was associated with lower CRN amplitude, reflecting hypo-monitoring of correct responses (F(4, 32) = 4.76, P < .05, 95% CI [0.01, 0.02]), and with greater OCDS severity (F(3, 36) = 3.32, P < .05, 95% CI [0.03, 0.19]).

The current findings provide evidence for differential, ERP-indexed inhibitory control and self-monitoring profiles across impulsive and compulsive phenotypes in OCDSs.

Evaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.

Healthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.

Thirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.

Single doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.

In the present study, we aimed to perform a systematic review evaluating the cognitive performance of patients with hoarding disorder (HD) compared with controls. We hypothesized that HD patients would present greater cognitive impairment than controls.

A systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit. The search terms were “hoarding disorder,” “cognition,” “neuropsychology,” “cognitive impairment,” and “cognitive deficit.” We included original studies assessing cognitive functioning in patients with HD.

We retrieved 197 studies initially. Of those, 22 studies were included in the present study. We evaluated 1757 patients who were 41 to 72 years old. All selected studies comprised case–control studies and presented fair quality. Contrary to our hypothesis, HD patients showed impairment only in categorization skills in comparison with controls, particularly at confidence to complete categorization tasks. Regarding attention, episodic memory, working memory, information-processing speed, planning, decision-making, inhibitory control, mental flexibility, language, and visuospatial ability, HD patients did not show impairment when compared with controls. There is a paucity of studies on social cognition in HD patients, although they may show deficits. The impact of emotion in cognition is also understudied in HD patients.

Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls. Further work is needed to explore social cognition and the impact of emotion in cognitive performance in HD patients.

Attentional problems are common and have been associated with multiple psychiatric disorders. This study examined problems of sustained attention across a range of psychiatric disorders using a validated computerized trans-diagnostic attentional paradigm (a continuous performance task). We hypothesized that multiple psychiatric disorders, particularly attention deficit hyperactivity disorder (ADHD), would be associated with pronounced attentional problems.

Totally, 576 non-treatment seeking participants (aged 18–29 years) were enrolled from general community settings, provided demographic variables, and underwent clinical assessments to detect mental health disorders. Each participant underwent the rapid visual information processing task, a validated computerized test measuring sustained attention. The two measures of sustained attention were the sensitivity index and target detection (proportion of targets detected). The profile of attentional deficits was examined across different disorders using z-scores relative to controls.

Participants with social phobia, obsessive-compulsive disorder (OCD), bulimia nervosa, and intermittent explosive disorder showed the greater impairment in target sensitivity, all with effect sizes of at least 0.8. Target detection was impaired across multiple disorders, with OCD and binge eating disorder exhibiting the most pronounced impairment. Post-traumatic stress disorder (PTSD) and compulsive sexual behavior were associated with particularly spared performance on both measures.

These data indicate that impaired attention is non-specific for ADHD and in fact several other disorders are associated with markedly larger deficits. Instead of clinicians assuming sustained attention problems are due to ADHD, a variety of disorders should be screened for when people report attentional problems. Future work should examine the contribution of comorbidities and psychoactive substances (prescribed or illicit) to the profiles identified.