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.

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.

According to Nemeth et al. (2011), pediatric mania is difficult to distinguish from childhood hyperactivity. Both share 3 common symptoms: distractibility, motoric hyperactivity, and talkativeness (Biederman, 2000). Oftentimes, children are referred from their pediatrician due to a lack of appropriate response to stimulant medication. Pediatricians have learned that merely raising the dose or changing the stimulant does not work. A thorough neuropsychological evaluation often reveals Bipolar Mania. They may have comorbid Bipolar Disorder and ADHD. This poster paper will examine measures that can assist in this important differential diagnosis as well as offer treatment options, including medication management.

This case study includes three pediatric patients diagnosed with Childhood Bipolar Disorder and ADHD. A comprehensive psychoeducational assessment was conducted for each of the patients, which resulted in this comorbid diagnosis.

One of the most helpful measures was the TOVA. When a child’s attention and impulsivity scores are normal, and response time and variability scores are abnormal, both on and off medication, that is an indication of a mood disorder (Nemeth et al., 2007). These children also performed poorly on measures of processing speed, and verbal learning and interference tasks (Henin et al., 2007). Measures of affect and personality were important diagnostically. A combination of Amantadine and either Clonidine HCL ER or Propranolol, as prescribed by a medical psychologist, were found to be effective in controlling the symptoms of this comorbid diagnosis.

An evaluation of children’s intellectual, attentional, behavioral, mood, and personality functioning is crucial for a differential diagnosis. In cases of comorbidity, ADHD and Childhood Bipolar Disorder, the sooner the child is on appropriate medications, the better. When just the surface diagnosis of ADHD is medicated, the outcome is often problematic. There may be a poor response to treatment and a higher rate of suicide.

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.

An open-label extension study (NCT02873208) evaluated the long-term tolerability, safety, and efficacy of combination olanzapine/samidorphan (OLZ/SAM) treatment in patients with schizophrenia. This qualitative sub study explored perceptions of benefit, burden, and satisfaction with previous medications and OLZ/SAM.

Semi-structured interviews (60 minutes; audio-recorded) were conducted. Interviewer sensitivity training, senior interviewer oversight, and a list of common medications to aid recall supported data collection. Interview transcripts were content coded and analyzed (NVivo v11.0).

All 41 patients reported a lifetime burden with schizophrenia adversely impacting employment, relationships, emotional health, social activities, and daily tasks. Hospitalization for schizophrenia management was another reported aspect of disease burden. Although most (n=32) patients reported previous medication benefits, side effects affecting physical, emotional/behavioral, and cognitive functioning were reported by all (n=41). Following OLZ/SAM treatment, 39/41 patients (95%) reported improvements in symptoms including hallucinations, paranoia, depression, sleep, and concentration. Furthermore, patients described improvements in self-esteem, social activities, relationships, and daily activities. Twenty-three patients (56%) reported side effects attributed to OLZ/SAM; lack of energy (n=12 [29%]) and dry mouth (n= 5 [12%]) were most common. Twenty-four (59%) patients were “very satisfied” with OLZ/SAM; most (n=35 [85%]) preferred to continue OLZ/SAM vs switching to another medication. As most substudy patients (n=40; 98%) completed the extension study, satisfied patients may be overrepresented in this analysis.

This qualitative interview approach provided valuable insight into patients’ experiences with previous medications and OLZ/SAM. Overall, most patients reported treatment satisfaction and improvements in symptoms, function, and health-related quality of life with OLZ/SAM.

Alkermes, Inc.

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

“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.

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.