To assess differences in cognitive impairment in a group of patients with schizophrenia receiving first-generation long-acting antipsychotics (FG-LAI) versus Aripiprazole long-actinginjectable (ALAI).

A descriptive, cross-sectional, multi-centerstudy.

Study sample: 28 outpatients with stable schizophrenia (18 men and 10 women) with ages ranging from 22 to 64years.

Inclusion criteria were: Clinically stable patients with a diagnosis of schizophrenia (according to DSM-5 criteria) and without any changes to their antipsychotic or antidepressant therapy in the last six months.

Simple stratified sampling was performed to collect data from patients with schizophrenia receiving FG-LAI (n=14) versus patients with schizophrenia receiving Aripiprazole long-acting injectable (ALAI) (n=14)

Groups were matched by age, gender, years of evolution of the disease, and years on formal education.

Functionality in the different cognitive domains was evaluated based on the Brief Assessment of cognition in Schizophrenia (BACS.), a hetero-applied instrument, which Spanish version has been validated. BACS evaluates the following cognitive domains:

Verbal memory (V.M): Word list test

Working memory (W.M): Digit sequencing task

Motor speed (M.S): Token motor task

Verbal fluency (V.F): Semantic or category fluency

Attention (A): Symbol coding

Executive function (E.F): Tower of London

The data obtained were analyzed using the SPSS 22.0 statistical package Differences between the means of quantitative variables were assessed using the independent-sample Student-t test. Individual test scores were converted into standardized (T and Z) scores and composite scores that were corrected for age and gender.

Informed consent was obtained from all patients according to the Declaration of Helsinki (World Medical Association).

In the group receiving ALAI, the most severely impaired cognitive domain was attention, whereas motor speed was barely affected. In contrast, verbal memory was most impaired, whereas motor speed was the least impaired cognitive domain in the group receiving FG-LAI.

Patients with schizophrenia taking ALAI showed a better cognitive function in all domains (except for motor speed and attention) than patients receiving FG-LAI.

Summarized results in Table1.

In our study, patients with schizophrenia receiving Aripiprazole long-acting injectable have better cognitive function than patients receiving first-generation long-acting antipsychotics.

To determine whether amphetamine extended-release oralsuspension (AMPH EROS) has an onset of effect at 30minutes postdose inchildren with ADHD.

This randomized, double-blind, 2-treatment, 2-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6 to 12 years withattention-deficit/hyperactivity disorder (ADHD) and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. A dose of 5 to 20mg/day of AMPH EROS was determined during a 1-week open-label phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received one day of double-blind active drug or placebo each in random sequence during 2 double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom session, returned to open label drug for 5days then crossed over on day 6 during a second double-blind laboratory classroom session. DB dose was fixed at AMPH EROS 15, 17.5, or 20mg . The primary endpoint was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham rating scale-combined score (SKAMP-C) at 30minutes postdose on two DB days. The key secondary endpoint was change from predose in the SKAMP-C score at 3hours postdose for AMPH EROS compared with placebo. Safety assessments included vital signs and adverse events.

Eighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30minutes and 3hours postdose, changes from baseline in SKAMP-C for AMPH EROS vs. placebo were statistically significant (p<0.01 and p=0.0002, respectively) with corresponding effect sizes of 0.96 and 1.57. Adverse events (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.

AMPH EROS was effective in reducing ADHD symptoms at 30minutes postdose. AEs were mild or moderate and consistent with those of other extended-release amphetamines.

Funding Acknowledgements: Support was provided by Tris Pharma, Inc.

Viloxazine ER (viloxazine extended-release capsules (Qelbree®) is a novel, nonstimulant, FDA-approved treatment for attention-deficit/hyperactivity disorder (ADHD) in adults and children ≥6 years of age. Viloxazine ER inhibits cytochrome P450-1A2, the enzyme responsible for caffeine metabolism. In a Phase 1 study, the peak exposure (Cmax) of caffeine was unchanged, while the systemic total exposure (AUC) was shown to increase ~5-fold following coadministration of caffeine (200mg) with viloxazine ER (900 mg/day x 4 days) compared to caffeine alone. Except for insomnia (44.4%), and possibly dizziness (8.3%), the incidence of adverse events (AEs) was not notably higher following coadministration vs. either caffeine or viloxazine ER alone. The objective of this analysis was to evaluate the impact of caffeine consumption on the incidence of AEs in adults with ADHD treated with viloxazine ER.

Data were analyzed from the Phase 3, double-blind (DB), placebo-controlled trial (NCT04016779) and ensuing (ongoing) open-label extension (OLE) safety trial (NCT04143217) supporting the viloxazine ER indication for adults with ADHD. Participants reported caffeine intake during the past week at each study visit.

Correlation was assessed between viloxazine ER dose (mg/day) and weekly total caffeine consumption (mg) and between ADHD Investigator Symptom Rating Scale (AISRS) Total score and caffeine consumption. Fifteen AE preferred terms, known to be associated with caffeine consumption, were evaluated. For viloxazine ER-treated subjects (200–600 mg/day) who experienced a potentially caffeine-associated AE, the probability the AE occurred as a function of viloxazine ER dose and caffeine consumption during the DB or OLE trials was estimated using a logistic regression model for AEs with an incidence ≥5%.

Of 372 enrolled subjects ~85% reported caffeine use during the DB trial; mean caffeine use was 1034 mg/week for the placebo group and 859 mg/week for the viloxazine ER group. There was no correlation between viloxazine ER dose and caffeine consumption (p=0.73), nor between AISRS total score and caffeine consumption (p=0.908). Of subjects reporting caffeine use, 44 (DB placebo), 79 (DB viloxazine ER), and 33 (OLE viloxazine ER) reported any of the pre-identified caffeine- associated AEs and were included in the regression analysis. For these subjects, insomnia-related AEs, fatigue, nausea, headache-related AEs, decreased appetite, and somnolence-related AEs occurred in ≥5% of viloxazine ER-treated subjects. Based on the regression analysis, caffeine consumption significantly increased the probability of experiencing insomnia-related AEs only (p=0.02).

This analysis suggests using caffeine concomitantly with viloxazine ER does not increase the likelihood of experiencing caffeine-related AEs except for insomnia. Still patients should be aware of the potential for viloxazine ER to augment caffeine exposure.

Supernus Pharmaceuticals, Inc.

Difficulties with emotion regulation have been associated with multiple psychiatric conditions. In this study, we aimed to investigate emotional regulation difficulties in young adults who gamble at least occasionally (ie, an enriched sample), and diagnosed with a range of psychiatric disorders using the validated Difficulties in Emotion Regulation Scale (DERS).

A total of 543 non-treatment-seeking individuals who had engaged in gambling activities on at least 5 occasions within the previous year, aged 18–29 were recruited from general community settings. Diagnostic assessments included the Mini International Neuropsychiatric Inventory, Minnesota Impulsive Disorders Interview, attention-deficit/hyperactivity disorder World Health Organization Screening Tool Part A, and the Structured Clinical Interview for Gambling Disorder. Emotional dysregulation was evaluated using DERS. The profile of emotional dysregulation across disorders was characterized using Z-scores (those with the index disorder vs. those without the index disorder).

Individuals with probable ADHD displayed the highest level of difficulties in emotional regulation, followed by intermittent explosive disorder, social phobia, and generalized anxiety disorder. In contrast, participants diagnosed with obsessive-compulsive disorder showed relatively lower levels of difficulties with emotional regulation.

This study highlights the importance of recognizing emotional dysregulation as a trans-diagnostic phenomenon across psychiatric disorders. The results also reveal differing levels of emotional dysregulation across diagnoses, with potential implications for tailored treatment approaches. Despite limitations such as small sample sizes for certain disorders and limited age range, this study contributes to a broader understanding of emotional regulation’s role in psychiatric conditions.

Combination olanzapine and samidorphan (OLZ/SAM) is in development for treatment of schizophrenia and bipolar I disorder and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension study (NCT02873208; ENLIGHTEN-2-EXT) in schizophrenia assessed the safety and tolerability of OLZ/SAM. Methods: Patients completing the 24-week, randomized, double-blind, phase 3 ENLIGHTEN−2 study comparing weight gain with OLZ/SAM vs olanzapine were eligible for ENLIGHTEN-2-EXT enrollment. Initial OLZ/SAM doses were based on olanzapine dose (10 or 20 mg) received at the conclusion of ENLIGHTEN-2; subsequent olanzapine dose adjustments were allowed. The samidorphan dose (10 mg) remained fixed throughout. Assessments included adverse events (AEs), weight, waist circumference, metabolic laboratory parameters, and Positive and Negative Syndrome Scale (PANSS) scores. Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.

265 patients received OLZ/SAM; 167 (63.0%) completed the extension study. Common AEs (= 5%) were weight decreased (n=23; 8.7%), extra dose administered (n=21; 7.9%), headache (n=18; 6.8%), and weight increased (n=16; 6.0%). At week 52, mean (SD) change from baseline for weight and waist circumference was −0.03 (6.216) kg and −0.35 (6.115) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. PANSS total scores remained stable during the extension.

OLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.

Alkermes, Inc.

Objective: NeuroStar® Advanced Therapy System is a transcranial magnetic stimulation (TMS) device with FDA-clearance for the treatment of Major Depressive Disorder (MDD) in adult patients who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode. With TMS, magnetic pulses are transmitted into the brain. Though the exact mechanism of action is unknown, it is postulated that resulting neuronal depolarization and changes in brain functional activity may be associated with various physiologic changes that lead to relief of depression in the indicated population. The type of magnetic field generated with TMS is not intended to induce a seizure during therapeutic use, but unintentional seizures have been reported during TMS treatment.

No seizures were reported with the use of the NeuroStar® system in clinical trials conducted prior to FDA clearance. The estimated risk of seizure in the NeuroStar® label is approximately 1 in 30,000 treatments or 1 in 1,000 patients. Since introduction of the NeuroStar® system into clinical practice, the rate at which seizures have been reported is even lower.

We conducted a review of literature that named the NeuroStar® Advanced Therapy System as the device used for TMS treatment and reviewed all seizure events reported to Neuronetics, Inc., directly or through FDA MedWatch through June 30, 2019. Articles reporting seizures in subjects with epilepsy during TMS treatment were excluded.

Previous comprehensive reviews of seizures induced by treatment with any TMS device by Wasserman et al. (1998) and Rossi et al. (2009) revealed that the rate of seizures is low. Many subjects that developed seizures during TMS had either received stimulation at parameters beyond current recommendations or had been predisposed to develop seizures in some way. Some of the events reported as seizures may, in fact, have been non-epileptic events.

Our literature review and analysis of seizures reported to Neuronetics, Inc. revealed that the rate of seizures during TMS treatment with the NeuroStar® appears to be lower than the rate that is published in the NeuroStar® Advanced Therapy prescribing information.

Seizures that take place during TMS treatment with the NeuroStar® system are rare. The rate of seizures reported directly to Neuronetics, Inc. is lower than that included in the NeuroStar® prescribing information. Our literature review validated seizures during TMS treatment with the NeuroStar® system reported in published literature have described either non-epileptic events (syncope) or occurred with risk factors for seizure induction, such as other predisposing clinical factors or treatment parameters outside the guideline recommend “safe” ranges.

Neuronetics, Inc.

Psychosis is defined as the presence of false beliefs or false perceptions. In children some causes of psychosis include psychiatric diagnosis such as schizophrenia and autism. However, it may also be secondary to medical conditions like various forms of encephalitis. Studies have shown that IVIG has been efficacious in the treatment of psychosis in the setting of autoimmune encephalitis.

A 9-year-old girl with a past medical history of Turner Syndrome, developmental delay, epilepsy, growth hormone deficiency, metabolic bone disease, and autism (ASD) presented with auditory and visual hallucinations that began June 2020. She began with her hearing voices that repeated the word “dead” and told her that she would not live. The hallucination later took the form of a man that would mock her, laugh about her parents dying, and tell her to kill them. The patient had associated symptoms of insomnia, anxiety, sadness, and increased anger. On her initial admission, CSF studies including culture and gram strain were unremarkable. NMDA, VHKC, and GAD65 antibodies were negative. At this time the hallucinations were thought to be due to ASD and she was prescribed Risperdal 0.25mg twice a day. Unfortunately, this did not improve her symptoms and from the time period of June 2020 to May 2021 she subsequently underwent trials of Risperdal, Zyprexa, Invega, Abilify, Thorazine, Haldol, and Clozaril. However, the symptoms persisted. Zoloft was prescribed, which was efficacious for anger and dysphoria. Trazodone, melatonin, and Remeron were tried for the treatment of insomnia, but did not cause enough improvement to continue the medications. Due to progression of command hallucinations with “the man” instructing her to hurt others, the patient was admitted July 2021 for administration of IVIG. Repeat CSF studies and brain MRI were unremarkable. From July 29, 2021 to August 1, 2021 she received three doses of IVIG which resulted in improvement of psychosis. Prior to administration, she was seeing “the man” throughout the day every single day, was sleeping only 3–4 hours a night, and having nightmares everyday. On evaluation 2 weeks after IVIG, she was only seeing “the man” 1–2 time a day, sleeping 6–8 hours a night, having nightmares 1–2 times a week, and her mood had improved.

This case illustrates the potential use of IVIG for the treatment of treatment-resistant psychosis. Although the cause of this patient’s symptoms remains unclear, there were clear benefits from the administration of IVIG that were not seen with trials of antipsychotics.

No Funding

Gambling disorder is common, affects 0.5–2% of the population, and is under-treated. Duration of untreated illness (DUI) has emerged as a clinically important concept in the context of other mental disorders, but DUI in gambling disorder, has received little research scrutiny.

Data were aggregated from previous clinical trials in gambling disorder with people who had never previously received any treatment. DUI was quantified, and clinical characteristics were compared as a function of DUI status.

A total of 298 individuals were included, and the mean DUI (standard deviation) was 8.9 (8.4) years, and the median DUI was 6 years. Longer DUI was significantly associated with male gender, older age, earlier age when the person first started to gamble, and family history of alcohol use disorder. Longer DUI was not significantly associated with racial-ethnic status, gambling symptom severity, current depressive or anxiety severity, comorbidities, or disability/functioning. The two groups did not differ in their propensity to drop out of the clinical trials, nor in overall symptom improvement associated with participation in those trials.

These data suggest that gambling disorder has a relatively long DUI and highlight the need to raise awareness and foster early intervention for affected and at-risk individuals. Because earlier age at first gambling in any form was strongly linked to longer DUI, this highlights the need for more rigorous legislation and education to reduce exposure of younger people to gambling.

To describe the presence of psychotic symptomatology in a patient with hyperthyroidism

Psychiatric-spectrum symptoms associated with thyrotoxicosis has been well reported in the past. However, psychosis in a patient with a thyroid nodule is a rare find. Here, the case of twenty four-year-old, single, unemployed, Albanian American male with self-reported history of Attention Deficit Disorder (ADD) and Cannabis use disorder was brought in to the Comprehensive Psychiatric Emergency Program (CPEP) due to new onset psychosis. Patient was paranoid, disorganized with labile mood. He had poor insight, judgement and impulse control. The event coincided with a period of unemployment in his life and new onset of hallucinations from past few days. He was brought in to the hospital after he was found pacing and having lack of sleep. Patient was treated with antipsychotic for acute psychosis. He was started on Risperidone initially to which he did not respond to. Blood work showed low TSH and elevated T4. Physical exam was noted for palpable thyroid nodule. Further labs resulted in high thyroid peroxidase antibody. Ultrasound of thyroid with color flow showed single nodule in the left lobe and iodine uptake activity localized to the left lobe. Patient was started on Methimazole 5 mg along with Haldol 5mg orally twice a day which improved his symptoms tremendously. Patient was stabilized and after 1 week was discharged on Haldol 5 mg by mouth two times a day for Psychosis, Cogentin 1 mg by mouth two times a day for extrapyramidal system (EPS), and Methimazole 5 mg by mouth daily for overactive thyroid nodule.

Psychosis associated with thyroid nodule is rare but possible. The onset of psychotic syndrome is an important clinical element whose underlying medical cause must be promptly clarified. Psychosis can present in a number of ways and can have different causes. Apart from psychiatric causes, underlying medical causes should always be considered. In this case it was important to get a full clinical history of the patient as well as complete physical examination. The differential diagnosis of a psychotic disorder in light of a medical disease should always be considered in order to promptly diagnose and treat the underlying cause to reduce the morbidity and possibly the mortality associated with it.

Panic disorder (PD) is a prevalent and impairing anxiety disorder with previous reports suggesting that the longer the condition remains untreated, the greater the likelihood of nonresponse. However, patients with PD may wait for years before receiving a guideline-recommended pharmacological treatment. The widespread prescription of benzodiazepines (BDZ) for managing anxiety symptoms and disorders might delay the administration of pharmacotherapy according to guidelines (eg, selective serotonin reuptake inhibitors, SSRIs). The present study aimed to determine the mean duration of untreated illness (DUI) in a sample of PD patients, to quantify and compare DUI-SSRI to DUI-BDZ, and to compare findings with those from previous investigations.

Three hundred and fourteen patients with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of PD were recruited from an Italian outpatient psychotherapy unit, and epidemiological and clinical variables were retrieved from medical records. Descriptive statistical analyses were undertaken for sociodemographic and clinical variables, Wilcoxon matched-pair signed rank test was applied to compare the distribution of DUI-SSRI vs DUI-BDZ, and Welch’s t test was performed to compare findings with those from previous studies.

The mean DUI-SSRI of the total sample was 64.25 ± 112.74 months, while the mean DUI-BDZ was significantly shorter (35.09 ± 78.62 months; P < 0.0001). A significantly longer DUI-SSRI, compared to findings from previous studies, was also observed.

The present results confirm a substantial delay in implementing adequate pharmacological treatments in patients with PD, and highlight the discrepancy between recommendations from international treatment guidelines and common clinical practice in relation to BDZ prescription.

To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response.

A post hoc analysis of pooled data from ASPIRE I and ASPIRE II evaluated ESK plus SoC vs PBO plus SoC in adults with MDSI without response (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at 24 hours after the first dose or at week 1 after the first two doses (ie, 24-hour and week 1 nonresponders). Response and remission (MADRS score ≤ 12) rates were assessed on day 25.

The analysis included 362 patients (n = 182, ESK plus SoC; n = 180, PBO plus SoC). Among 24-hour nonresponders, more patients receiving ESK plus SoC vs PBO plus SoC achieved response (63.9% vs 48.0%, P = .010) and remission (35.1% vs 24.4%, P = .074) at day 25. Odds of response/remission were higher with ESK plus SoC vs PBO plus SoC (response: 1.89, 95% CI, 1.17-3.05; remission: 1.48, 95% CI, 0.93-2.35). Similar findings were observed among week 1 nonresponders for response (48.4% vs 34.5%, P = .075), remission (25.0% vs 13.1%, P = .060), and odds of response/remission (response: 2.03, 95% CI, 1.22-3.40; remission: 1.63, 95% CI, 1.01-2.62).

Patients with MDSI not responding within the first week of treatment with ESK plus SoC may still benefit from a full 4-week treatment course.