Neurology and psychiatry have been linked together for a long period of time. One overlap demonstrated in the literature is the correlation between epilepsy with mood and psychosis. There is a big group of psychoses called the psychosis of epilepsy (POE); however, there is not much evidence about the diagnosis and management. Differentiation between POEs is difficult and is compounded by a lack of evidence-based guidelines on appropriate management. Even if you arrive at the diagnosis, POE can be difficult to manage. Some antiepileptic drugs (AEDs) cause psychiatric side effects and some antipsychotics may be epileptogenic. In this poster, we will discuss ways to diagnose and treat POE, as well as how to optimize certain AEDs in patients with POE.

Articles were chosen from multiple databases, such as MEDLINE, Google Scholar, and PsychInfo, to gather evidence about the diagnosis and management of POE. Specific keywords, such as Psychosis, Epilepsy, Antipsychotic, Antiepileptic, and Electroencephalogram (EEG) were used. Articles talking about recommendations regarding the use of AEDs and antipsychotics in POE were extracted from these databases.

POE includes preictal, ictal, postictal, and interictal psychosis. Preictal psychosis is very rare and tends to present with dissociation and déjà vu. This is correlated with temporal lobe epilepsy and resolves after the seizure. Ictal psychosis will correspond with epileptic activity on EEG and can manifest as aggression, delusions, or hallucinations. Antipsychotics are contraindicated in this POE. Postictal psychosis usually presents as a combination of mood symptoms and grandiose delusions seen with interictal sharp epileptiform discharges on EEG. Interictal psychosis can be subtyped into brief and chronic, with brief occurring during periods of increasing seizure frequency and chronic having no association with seizures. They both present similar to symptoms seen in classic schizophrenia and antipsychotics are often utilized.

Clozapine and chlorpromazine were found to have the highest seizure prevalence from second- and first-generation antipsychotics respectively, and the lowest was found with risperidone. AEDs that are commonly used in psychiatry, such as oxcarbazepine, carbamazepine, valproic acid, and lamotrigine are discussed in detail regarding their optimal dosing strategy for patients presenting with POE.

Diagnosis and management of the various types of POE can be challenging due to the lack of literature. We recommend using the antipsychotic, risperidone, as it has shown to have the lowest seizure prevalence among all antipsychotics. Both neurologists and psychiatrists should keep POE on their differential when dealing with seizure patients with psychosis. It is crucial for psychiatrists to understand how to optimize AEDs in the management of POE as these patients are often seen on the consult service.

No Funding

Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.

This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.

When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.

This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.

These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.

Tinnitus not heretofore been described as the only manifestation of delusional possession in Kandinsky-Clerambault syndrome. Such a case is presented.

Case Report: A 70-year-old left handed (pathological) man, eight years prior to presentation, noted gradual onset of decreased hearing and high- pitched constant tinnitus AU made worse with stress. Initially only present in quiet, it intensified, ultimately present in all situations, even with ambient background noise. He believed that the Devil was inside of his head, had been there for many years, and was making his life unbearable by subjecting him to the tinnitus. Other than the tinnitus, the devil did not cause any other symptoms, nor did it communicate with him in any fashion. In an effort to eliminate the Devil-induced tinnitus, he twice attempted suicide through self-strangulation. The tinnitus persisted despite treatment with mirtazapine and lumateperone.

Abnormalities in physical examination: General: Decreased blink frequency. Continuous fidgeting and generalized tremulousness. Neurological examination: Mental status examination: Hypoverbal. Able to remember 5 digits forwards and 3 digits backwards. Unable to remember any of four objects in 3 minutes with and without reinforcement. Presidents as follows: Biden, Obama, ?. Animal Fluency Test: 7 (Abnormal). Cranial Nerve (CN) Examination: CN I Alcohol Sniff Test: 0 (Anosmia). CN VIII Calibrated Finger Rub Auditory Screening Test: Strong 2 AU. Motor Examination: 1+ cogwheel rigidity in the right upper extremity. Gait Examination: Unstable tandem gait. Reflexes: 1+ throughout. Other: Tinnitus Severity Questionnaire : 38/40 (Severe tinnitus). Tinnitus Handicap Inventory: 94/100 (Grade 5- Catastrophic handicap).

While Kandinsky Clerambault Syndrome, Delusion of Possession Syndrome is uncommon in the United States (Dimkov, 2020; Enoch, 2020), 46% of Italians believe in the Devil (Marra, 1990) and 0.6% of Canadians believe that they have been possessed by a demon (Ross & Joshi, 1992). Although the most common neurological presentation of Kandinsky Clerambault syndrome is glossolalia, sensory phenomenon of anosmia (Chand et al, 2000; Medeiros De Bustos et al, 2014), ageusia (Chand et al, 2000), kinaesthesia (Gedevani et al, 2022), allochiria (Medeiros De Bustos et al, 2014), synesthetic neuralgia (Medeiros De Bustos et al, 2014), cenesthesia (Medeiros De Bustos et al, 2014), pain (Medeiros De Bustos et al, 2014) and anaesthesia (Yap, 1960) have also been described. While tinnitus has not been reported with Kandinsky Clerambault, it has been noted to occur with depression, anxiety (Zöger et al, 2006; Salviati et al, 2013), and psychosis (Frankenburg & Hegarty, 1994; Jain et al, 2017). Given the widespread belief in the general population of the Devil and possession by external entities, assessment of presence of Kandinsky Clerambault Syndrome in those with intractable tinnitus may be worthwhile.

No Funding

Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), among other symptoms. Previous studies of narcolepsy have largely relied on quantitative methods, providing limited insight into the patient experience. This study used qualitative interviews to better understand this rare condition.

Patients with narcolepsy (types 1 [NT1] and 2 [NT2]) were recruited using convenience and snowball sampling. Trained qualitative researchers conducted hour-long, individual interviews. Interview transcripts were coded and thematically analyzed using inductive and deductive approaches.

Twenty-two adults with narcolepsy (NT1=12; NT2=10) participated (average age: NT1=35; NT2=44). Most were female (NT1=83%; NT2=70%) and white (NT1=75%; NT2=60%). Average times since diagnosis were 7 years (NT1) and 11 years (NT2).

At disease onset, symptoms experienced included EDS (NT1=83%; NT2=80%)—sometimes involving sleep attacks (NT1=35%; NT2=50%)—fatigue (NT1=42%; NT2=30%), oversleeping (NT1=33%; NT2=20%), and cataplexy (NT1=42%). Participants sought a diagnosis from healthcare professionals including sleep specialists, neurologists, pulmonologists, psychiatrists, and primary care physicians. Many participants reported receiving a narcolepsy diagnosis >10 years after symptom onset (NT1=50%; NT2=60%). During that time, patients reported misdiagnoses, including depression, sleep apnea, and attention-deficit/hyperactivity disorder.

Common symptoms included EDS (NT1=100%; NT2=90%), cognitive impairment (NT1=92%; NT2=100%), and fatigue (NT1=75%; NT2=90%). All participants with NT1 reported cataplexy. Participants rated these symptoms as among the most bothersome.

Study results provide descriptions of narcolepsy symptoms and the often challenging journey toward seeking a diagnosis. By using patient-centered, qualitative methods, this study fills a gap by providing additional insights into the patient experience of narcolepsy.

Alkermes, Inc.

The incidence of delirium in the ICU occurs upwards of 80% and is associated with increased length of stay in hospitals and mortality. The effects of previously recommended antipsychotics and benzodiazepines for management of ICU delirium have come into question as they have been associated with no change in or even exacerbation of delirium. This has led to unclear pharmacological treatment recommendations and the need to seek explicit treatment of ICU delirium. Dexmedetomidine, an adrenergic alpha 2 receptor agonist, has been shown to reduce the development of delirium and improve the resolution of delirium. The aim of this review is to explore the evidence that supports the use of dexmedetomidine for treatment and prevention of hyperactive delirium in ICU patients.

A literature review using articles from databases such as PubMed and Google Scholar was conducted to gather supporting evidence on the use of dexmedetomidine in ICU delirium. The articles included in this review were randomized controlled trials (RCT), observational studies, systematic reviews and meta-analyses, and literature review articles. The main outcomes measured included a decrease in scales used to measure delirium and agitation, time spent in delirium, duration of mechanical ventilation, and incidence of delirium.

A RCT comparing the use of lorazepam and dexmedetomidine in 106 adult mechanically ventilated ICU patients demonstrated that dexmedetomidine at 0.15- 1.5 μg/kg/h resulted in more days without delirium. Another study done to compare the efficacy and safety of prolonged sedation in 375 mechanically ventilated patients found that individuals receiving dexmedetomidine at a rate of 0.2-1.4 μg/kg/h spent less time on the ventilator, developed delirium 20% less often, and were off mechanical ventilation almost 2 days sooner compared to midazolam. The Dexmedetomidine to Lessen ICU Agitation RCT, which involved 74 adults treated at rate of 0.5-1.5 μg/kg/h in whom extubation was not done due to delirium severity, demonstrated that dexmedetomidine increased ventilator free hours by 17 hours compared to placebo. Another RCT of 100 delirium-free ICU adults demonstrated a greater proportion of patients who remained delirium-free during the ICU stay after administration of nocturnal dexmedetomidine at rate of 0.2-0.7 μg/kg/h. A case series done to explore the use of dexmedetomidine in post-traumatic brain injury (TBI) showed dexmedetomidine at a rate of 0.49 μg/kg/h in 85 patients with severe TBI did not worsen neurological function.

Delirium in ICU patients occur at exceptionally high rates and there is a need for clear pharmacologic treatment. Current literature supports the use of dexmedetomidine for reduction of delirium in ICU patients with potential to eliminate risk associated with previously used antipsychotics and benefits of safe use in TBI, decreased risk of polypharmacy and overall mortality associated with ICU delirium.

No Funding

Zuranolone is an investigational positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and a neuroactive steroid in clinical development as a once-daily, oral, 14-day treatment course for adults with major depressive disorder or postpartum depression (PPD). The randomized, double-blind, placebo-controlled SKYLARK Study (NCT04442503) demonstrated that zuranolone 50 mg significantly improved depressive symptoms (as assessed by 17-item Hamilton Rating Scale for Depression total score) at Day 15 (primary endpoint; p<0.001) and was generally well tolerated in adults with PPD.

In the SKYLARK Study, patients were randomized 1:1 to receive zuranolone 50 mg or placebo for 14 days. Safety and tolerability were assessed by the incidence and severity of treatment-emergent adverse events (TEAEs), rates of dose reduction and treatment discontinuation, as well as weight gain and sexual dysfunction.

The SKYLARK Study assessed safety data from 98 patients treated with zuranolone 50 mg and 98 patients treated with placebo. TEAEs were reported in 66.3% of zuranolone-treated patients and 53.1% of placebo-treated patients. In patients that experienced TEAEs, most reported mild (zuranolone, 50.8%; placebo, 75%) or moderate (zuranolone, 44.6%; placebo, 23.1%) events. The most common (≥5%) TEAEs were somnolence (26.5%), dizziness (13.3%), sedation (11.2%), headache (9.2%), diarrhea (6.1%), nausea (5.1%), urinary tract infection (5.1%), and COVID-19 (5.1%) with zuranolone, and headache (13.3%), dizziness (10.2%), nausea (6.1%), and somnolence (5.1%) with placebo. Dose reduction due to TEAEs was 16.3% in patients receiving zuranolone vs 1.0% in patients receiving placebo; the most common TEAEs (>1 patient) leading to zuranolone dose reduction were somnolence (7.1%), dizziness (6.1%), and sedation (3.1%). Treatment discontinuation due to TEAEs was 4.1% in patients receiving zuranolone vs 2.0% in patients receiving placebo; TEAEs leading to zuranolone discontinuation in >1 patient included somnolence (2.0%). Serious TEAEs were reported in 2.0% of zuranolone-treated and 0% of placebo-treated patients; these included upper abdominal pain (1.0%, [1/98]), peripheral edema (1.0%, [1/98]), perinatal depression (1.0%, [1/98]), and hypertension (1.0%, [1/98]). Per investigators, serious TEAEs were not related to zuranolone. No signals for weight gain or sexual dysfunction were identified.

In adults with PPD, zuranolone 50 mg was generally well tolerated. Most TEAEs were mild or moderate in severity. Dose reduction due to TEAEs mainly resulted from somnolence, dizziness, and sedation, while treatment discontinuation due to TEAEs was low. No signals for weight gain or sexual dysfunction were identified.

Sage Therapeutics, Inc., and Biogen Inc.

The dextroamphetamine transdermal system (d-ATS) was developed as an alternative to current oral formulations of amphetamine, which is a first-line treatment for ADHD. In a randomized controlled trial of d-ATS in children and adolescents with ADHD, the primary endpoint (SKAMP total score) and secondary endpoints were met. This analysis evaluated the efficacy of d-ATS using SKAMP total score by optimized dose, gender, age group, ADHD type, and baseline ADHD severity.

This study comprised a 5-week, open-label dose-optimization period (DOP) followed by a 2-week, randomized, cross-over double-blind treatment period (DBP). All eligible patients received d-ATS 5 mg/9hr, with weekly evaluation for dose increase to 10 mg/9hr, 15 mg/9hr, and 20 mg/9hr. Once reached, the optimal dose was maintained for the DOP and used during the DBP. Preplanned subgroup analyses of mean SKAMP total score by optimized dose, gender, age group, ADHD type, and baseline ADHD severity were conducted. Efficacy was assessed by difference (d-ATS vs placebo) in least-squares (LS) mean SKAMP total score from a mixed-model repeated-measures (MMRM) analysis and is reported throughout as LS mean (95% confidence interval [CI]).

In total, 110 patients were enrolled in the DOP, and 106 patients were randomized in the DBP. During the DOP, three patients reported 3 TEAEs that led to study discontinuation (irritability, appetite loss, abdominal pain). The difference (d-ATS vs placebo) in LS mean SKAMP total score was -5.9 (-6.8, -5.0), with differences in attention, deportment, and quality of work sub-scores of -1.4 (-1.7, -1.1), -1.9 (-2.2, -1.5), and -1.3 (-1.5, -1.0), respectively. Patients receiving d-ATS at each optimized dose demonstrated improvements vs placebo in LS mean SKAMP total score (-7.3 [-10.8, -3.7], -4.5 [-6.0, -3.0], -5.9 [-7.4, -4.5], -7.6 [-9.6, -5.6] at 5, 10, 15, and 20 mg/9hr, respectively). Both male and female patients experienced improvements vs placebo in SKAMP total score. The observed difference was greater in males (-6.3 [-7.3, -5.2]) vs females (-5.0 [-6.6, -3.4]). Similarly, improvements vs placebo were seen in patients with combined type ADHD and in those with predominantly inattentive type ADHD, with an observed LS mean difference of -8.0 (-9.2, -6.8) for the combined type and -3.3 (-4.6, -2.1) for the inattentive type. In addition, patients demonstrated improvement during the DBP regardless of baseline ADHD severity. The difference in LS mean SKAMP total score was -4.5 (-5.9, -3.1) for patients with a baseline SKAMP total score of 0-36 and -6.7 (-7.9, -5.6) for those with a baseline SKAMP score of 37-54.

d-ATS was effective and generally well-tolerated in treating ADHD in children and adolescents regardless of optimized dose, gender, age group, ADHD type, or baseline ADHD severity.

Noven Pharmaceuticals, Inc.

Major depressive disorder (MDD) is the second leading cause of disability in the US, and increases the risk of poor health outcomes. This analysis assessed the real-world benefit and availability of esketamine for patients with difficult-to-treat MDD.

Data were drawn from the Adelphi Real World Depression Disease Specific Programme XII (DSPTM), a cross-sectional retrospective survey of physicians and their patients in the United States in 2022. Physicians reported details for patients with MDD receiving esketamine regarding their prescribed medication (including access), daily functioning and disease improvement whilst receiving esketamine (reported by Clinical Global Impression Improvement Scale (CGI-I)),)) change in depression severity (reported by Clinical Global Impression Severity Scale (CGI-S)) and physician satisfaction. CGI-I responses measured level of disease improvement since the initiation of current depression treatment regimen (‘Very much worse=1’ to ‘Very much improved=7’). CGI-S response options were converted to numerics to measure level of severity change (‘Normal, not at all ill=0’ to ‘Among the most extremely ill patients=6’) and compared at time of esketamine initiation and currently. Physician satisfaction with medication’s ability to achieve patient treatment goals was derived from a numeric scale (where ’Not at all satisfied=1’ to ’Very satisfied=5’).

94 patients with MDD were currently receiving esketamine. Mean age was 44.3 (SD 13.26) and 47% were male. 26% of patients had been receiving esketamine for 0-3 months, 5% for 3-6 months, 15% for 6-12 months, 23% for 1-2 years and 30% for more than 2 years. CGI-I results showed physicians rated depression as improved in 98% of patients receiving esketamine >30 days. CGI-S results showed that patients receiving esketamine 1-30 days had a mean improvement of 1.2 while patients receiving esketamine for >30 days showed mean improvement of 0.9. 80% of physicians reported high satisfaction (score of 4 or 5) with esketamine’s ability to achieve patient treatment goals.

In patients receiving esketamine >30 days physicians reported that 62% could function better socially, 53% had a better quality of life, 41% had increased ability to work, 37% could better meet their own basic needs and 34% had an improvement in overall general health.

When prescribing esketamine, the treatment was only “available without restrictions” for 18% of patients, whilst 82% experienced at least some restrictions.

Physicians reported rapid and sustained clinical improvement among patients with MDD treated with esketamine in this real-world survey.

The analysis described here used data from Adelphi Real World Depression DSP. The DSP is a wholly owned Adelphi Real World product. Janssen is one of the multiple subscribers to the DSP.

Centanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) that has demonstrated efficacy, safety, and tolerability vs placebo (PBO) in adults with ADHD in 2 pivotal phase 3 trials (Adler LA, et al. J Clin Psychopharmacol. 2022;42:429-39).

Pooled data from 2 double-blind, multicenter, PBO-controlled trials enrolling adults (18–55 years) meeting DSM-5 ADHD criteria were analyzed. Patients were randomized 1:1:1 to CTN sustained release (SR) 200 mg or 400 mg total daily dose (TDD) or matching PBO if Adult ADHD Investigator Symptom Rating Scale (AISRS) score was ≥28 at screening (if not receiving pharmacologic ADHD treatment) or ≥22 at screening and ≥28 at baseline (if receiving treatment). Having had no prior benefit from ≥2 ADHD therapies of different classes, use of prohibited medications, and positive alcohol/drug screens were exclusionary. Studies had 4 periods: (1) screening and washout (≤28 days), (2) single-blind PBO run-in (1 week), (3) double-blind treatment (6 weeks), and (4) follow-up (10 days after last dose). Patients with ≥30% Adult ADHD Self-report Scale (ASRS) improvement from start to end of screening were screen failures; those with ≥30% ASRS improvement from start to end of PBO run-in were terminated early. A mixed model for repeated measures analysis evaluated CTN SR vs PBO based on ADHD treatment history; least squares mean (LSM) change from baseline (BL) in AISRS at day 42 was the outcome of interest.

In total, 859 patients were analyzed (CTN SR 200 mg TDD, n=287; 400 mg TDD, n=287; PBO, n=285). LSM change from BL in AISRS score was significant at day 42 for each CTN SR TDD group (both, P<0.001) in the overall population vs PBO. Among patients with prior stimulant/nonstimulant treatment (n=542), LSM change from BL was significant at day 42 vs PBO in the CTN SR 200 mg (P=0.016) and 400 mg (P=0.008) TDD groups. Although cohort size was limited (n=47), LSM change from baseline with CTN SR 400 mg TDD was significant (P<0.05) from days 14 to 42 in those who took 2 prior stimulant/nonstimulant treatments, with P=0.030 at day 42. In those with no prior stimulant/nonstimulant treatment (n=317), LSM change from BL was significant at day 42 for the CTN SR 200 mg (P=0.007) and 400 mg (P=0.008) TDD groups vs PBO. When analyzed by history of any past stimulant use, LSM change from BL was significant at day 42 for CTN 200 mg (n=179; P=0.013) and 400 mg (n=166; P=0.006), with significance (P<0.05) noted at day 7 (200 mg TDD) and at day 21 (400 mg TDD), remaining significant to day 42.

This pooled analysis suggests that CTN SR treatment is efficacious in adults with ADHD, regardless of prior treatments, an encouraging finding given reported adult ADHD treatment patterns.

Study Registration: NCT03605680, NCT03605836

Otsuka