CerefolinNAC (CFLN-NAC) contains L-methylfolate (6 mg), methylcobalamin (2 mg), and N-acetylcysteine [NAC] (600 mg) [Pamlab 2017]. Dizziness and lightheadedness have not heretofore been described with use of CFLN-NAC.

Case Study: A 64 year old right-handed female was started on CFLN-NAC for smell and taste issues. Over a three day period, she experienced a gradual increase in dizziness. This was a non-vertiginous lightheadedness, so severe that she was unable to walk, and would lie down the entire day to alleviate the dizziness. It was associated with nausea, but without any vomiting or falls. The dizziness would come and go, last for several hours, and was 9/10 in severity.

She admits to a past history of epochs of vertigo. The vertigo occurred three times with nausea and vomiting 13 years, 11 years, and 4 years prior to presentation. She also developed a constant, bilateral, high-pitched tinnitus 14 years prior to presentation, which obstructs her hearing. It is level 3/10 in intensity during the night and in the quiet. There were no alleviating or aggravating factors. Acupuncture was without effect, and she denies any ear pain. After ceasing CFLN-NAC for three days, a gradual reduction of dizziness to baseline ensued.

Abnormalities in Physical Examination: General: Decreased blink frequency and hypokinesia. Cranial Nerve III, IV, VI: Saccadization of horizontal eye movements. Motor Examination: Tone: 1+ cogwheel rigidity in both upper extremities, left more than right. Drift Test: Bilateral Abductor Digiti Minimi sign with cerebellar spooning. Reflexes: Absent quadriceps femoris and Achilles bilaterally. Positive Hoffman reflex bilaterally. Neuropsychiatric Testing: Go-No-Go Test: 6/6 (normal). Animal Fluency Test: 19 (normal). Reliable Digit Span: 10 (normal). Clock Drawing Test: 4 (normal). Center for Neurologic Study Lability Scale: 10 (normal). Other: Audiometry and Fiberoptic Endoscopy: normal. MRI of the brain with and without contrast was normal.

None of the individual components in CFLN-NAC have been reported to precipitate dizziness [Pamlab 2017]. The non-vertiginous nature of the dizziness makes it unlikely to be due to vestibular involvement, raising the spectre of this drug having an impact on the autonomic nervous system. While a nocebo effect could be in action, this is unlikely since dizziness was not presented as a potential side effect on initiation of the medication. In addition, methylcobalamin can cause hyperviscosity syndrome, but due to an absence of visual disturbances and altered mental status, it is also improbable. The relatively rapid onset with initiation and resolution upon discontinuation of this medication strongly suggests that it is not a coincidence, rather an origin for the dizziness. Those who are treated with CFLN-NAC should be queried as to new onset dizziness. For those already dizzy, one should consider other treatment options.

Smell and Taste Treatment and Research Foundation

Flibanserin, a serotonin antagonist currently indicated for treatment of female sexual dysfunction disorder, has not heretofore been described to worsen cerebellar function. Such a case is presented.

A 60-year-old woman, 8 months prior to presentation, had an acute onset of fainting and hitting her head into a wall without loss of consciousness. She could not stand up, had left-sided weakness, and vomiting, with garbled, slow speech and severe headache. Findings in the emergency room showed a left cerebellar parenchymal hemorrhage of 3.2 x 3.1 x 2 cm with the epicenter at the dentate nucleus, extending medially towards midline into the cerebellar vermis, with surrounding perilesional edema extending into the middle cerebellar peduncle. Also, 5.2 cm of the hemorrhage extended from the petrous of the tentorium to the cerebellar vermis. Moreover, a ventral left thalamic hemorrhage with subependymal clot at the foramen of Monroe extended into the dependent portion of lateral ventricles without midline shift. Post one month of physical therapy, speech, walking, and coordination improved but she continued to have delayed speech and trouble getting up, with a wide stance.

Neurologic Examination: Cranial Nerve (CN) Examination: CN XI: Sternocleidomastoid hypertrophy, horizontal titubation. Motor examination: Drift test: L pronator drift with L abductor digiti mini sign. Gait examination: heel walking, dystonic posture of L hand. Tandem gait: unstable, wide based. Cerebellar examination: Both (B) finger-to-nose dysmetria, Left > Right. Slow rapid alternating movements (RAM) L Upper Extremity (UE). Due to absent sexual desire she started 100 mg of flibanserin nightly. Maintaining this for 5 weeks, her coordination markedly worsened with poor balance and a need for a cane to ambulate. She would stumble, with a wider gait, and found climbing stairs challenging. Physical examination displayed worse cerebellar function: prominent horizontal titubation. Finger-to-nose—dysmetria L>R. Decreased RAM, L UE. Markedly positive Holmes Rebound phenomenon, Bilateral UE. Tandem gait: unstable. A week post stopping flibanserin, gait and cerebellar examination returned to baseline.

The temporal correlation between the use of flibanserin and transient worsening of cerebellar function strongly suggests that this is the causative agent. Since serotonin is essential in cerebellar function, including its action on the cerebellar cortex and deep cerebellar nuclei, it strongly suggests that its action as a serotonin antagonist is the mechanism whereby flibanserin is causing cerebellar symptoms. In those on flibanserin, investigation to detect the presence of cerebellar dysfunction is warranted. Assessment for the presence of cerebellar dysfunction in those who are on anti-serotonin drugs, such as cyproheptadine and methysergide, may be worthwhile.

No Funding

Restraint and seclusion were considered a form of treatment but consistently has led to physical and mental injuries to staff and patients. De-escalation has been viewed as a safer option. Understanding which intervention yields decreased injuries, aggression and violence will guide policy and inform practice.

To identify which intervention leads to decreased physical and psychological injury to patients and staff.

The frequency of physical injuries to patients and staff from aggressive patients; frequency of psychological injuries to patients and staff from violent, aggressive incidents; frequency of violence, agitation and aggression; competence of staff at managing aggression and violence were evaluated.

Fourteen studies were included in this review. There are many forms of de-escalation. Studies where techniques were taught to staff, the intervention was effective in decreasing injury in approximately half the studies. De-escalation techniques taught to patients decreased injury in 100% of the studies included in this review.

Consensus on which intervention works best could not be reached, nor is there overwhelming evidence for a particular type of de-escalation better suited for decreasing aggression and violence. Caution should be exercised when choosing a de-escalation technique for implementation in institutions due to lack of regulating agencies that inform practice and standards. In addition, the literature lacks best practices for de-escalation techniques backed by evidence. Restraint and seclusion should be used as a last resort due to inherent risk associated with the intervention.

Anxiety disorder is one of the common mental health problems in college students, which hurts their study, work, and life. Comprehensive psychological crisis intervention is a complete psychological treatment method expected to be essential in treating anxiety disorders in college students.

One hundred college students with anxiety disorder were selected as research subjects and randomly divided into two groups. The experimental group received comprehensive psychological crisis intervention treatment and comprehensive intervention measures such as psychological assistance, cognitive behavioral therapy, and intimate relationship training. The control group received traditional psychotherapy, including counseling and medication. The Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and other assessment tools were used to carry out psychological measurements of the two groups of patients before, after, and at the follow-up point, respectively. The collected information was statistically analyzed by SPSS23.0 software.

After the comprehensive psychological crisis intervention treatment, the anxiety and depression levels of the experimental group were significantly reduced (P<0.001), and life satisfaction was significantly increased (P<0.001). Compared with the control group, the experimental group showed obvious advantages in curative effect.

Comprehensive psychological crisis intervention has shown remarkable efficacy in college students with anxiety disorders, can effectively reduce anxiety and depression, and improves the life satisfaction of patients. This approach may become an essential option for treating anxiety disorders in college students.

2021 Humanities and Social Sciences Research Project for Basic Research Business Expenses of Provincial Undergraduate Universities in Heilongjiang Province. No. 2021- kyywf-0384.

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.

Slow release is a fundamental feature of long-acting injectable (LAI) antipsychotics. This property allows continuous drug exposure between dosing intervals. However, there can be a significant delay between giving the first LAI dose and achievement of efficacious plasma concentrations. This time period requires additional pharmacologic intervention. Until now, this delay was addressed with one of two strategies: 1) continuing with supplemental oral antipsychotic, or 2) giving more LAI up front (e.g. loading dose). A third strategy has now been developed to reduce the time needed for oral supplementation when starting the LAI aripiprazole lauroxil (AL) from 21days to 1day. A nano-crystalline milled dispersion of AL (ALNCD; brand name ARISTADA INITIO™) was formulated by reducing the AL particle diameter from micron-size particles to nanometer- sized particles. ALNCD has faster dissolution and a shorter half-life than AL and is designed to be used as a single injection along with a single oral aripiprazole dose of 30mg as a 1-day alternative to the 21days of oral aripiprazole supplementation. Here we provide an overview of the new 1-day initiation regimen for starting AL treatment, and demonstrate the relative contributions of each of its components.

A blinded, randomized, phase 1, pharmacokinetic (PK), and safety study compared the 1-day initiation regimen with the 21-day oral aripiprazole regimen. A combination of observed data, and population pharmacokinetic model–based simulations were used to plot plasma aripiprazole concentrations of single doses of ALNCD, 30mg oral aripiprazole, and AL, individually, and all three combined.

The PK profiles of the 1-day and 21-day initiation regimens (both in conjunction with either 441mg or 882mg doses of AL) were comparable, with therapeutically relevant aripiprazole levels achieved within 4days of treatment initiation. The safety profile of the 1-day initiation regimen was similar to the 21-day initiation regimen, and consistent with that of AL. Aripiprazole concentration–time profiles demonstrated that each component delivered aripiprazole to the systemic circulation at different time periods, with the 30mg dose of oral aripiprazole predominant in the first week, followed by ALNCD, and then AL.

The 1-day initiation regimen is well-tolerated and a suitable alternative to 21days of oral aripiprazole supplementation for starting AL. Each component of the 1-day initiation regimen, together with AL, is necessary to provide continuous coverage from treatment initiation until the next regularly scheduled AL injection.

Funding Acknowledgements: This study was funded by Alkermes Inc.

Borderline personality disorder is a common psychological disorder, especially among college students. Red culture is an important historical and cultural aspect of China, with rich educational significance. Red culture identity education plays an important role in university education, but its effectiveness for students with borderline personality disorder has not been fully studied.

A total of 100 college students with borderline personality disorder were selected as experimental subjects and divided into two groups, respectively receiving art design education and routine education. Data were collected by the Stanford Acute Stress Response Questionnaire (SASRQ) and the 3-minute Delirium Diagnostic Scale (3D-CAM) and statistically analyzed using SPSS23.0 software.

The results showed that after participating in red culture identity education, the mental health status of students with borderline personality disorder was significantly improved. They exhibit higher emotional stability, self-confidence, and a sense of self-worth. At the same time, they are also more willing to express themselves and have a deeper understanding and identification with the core socialist values.

Art and design education can effectively improve the level of red cultural identity of college students with borderline personality disorder. The collaborative educational approach of art and design education can help college students with borderline personality disorder better adapt to the social environment, and enhance their mental health and self-development ability. Therefore, educational psychology should incorporate art and design education into the education plans of students with borderline personality disorders to promote the development of their red cultural identity.

Meningitis causes inflammation of the meninges and when bacteria are not the cause may be considered aseptic. Drug-induced aseptic meningitis (DIAM) can arise from the use of certain medications. The pathophysiology of DIAM is not well understood. Within the antiepileptic medication class, only lamotrigine, carbamazepine, and levetiracetam have been associated with DIAM via documented cases. Common presentation of DIAM involves fever, headache, meningismus, and mental status changes (abnormal consciousness and focal neurological deficits). Other clinical features may include neck stiffness, photophobia, nausea, vomiting, abdominal pain, bone pain, hypotension, edema (facial and optic nerve), rash, and seizures. Case reports of DIAM with varying or limited symptomology exist. Therefore, the presentation alone will not allow for a DIAM diagnosis, prompting further analysis and diagnostic exclusion.

A middle-aged male presented with a 48-hour history of confusion, disorientation, unresponsiveness, and hypersomnolence. Past medical history included hypertension, hyperlipidemia, type-2 diabetes, and seizures. Home medication included chlorthalidone, levetiracetam, lisinopril, metformin, potassium chloride, rosuvastatin with no medication allergies reported. Upon admission, the patient denied fever, headache, nausea, neck pain, vomiting, and rash. Somnolence, dysarthria, and obtundation were noted during the physical evaluation. Hospital medications included home medications along with enoxaparin, correctional dose insulin lispro, and IV lactated ringers. Vitals and labs were unremarkable. On hospital day (HD) 1 the MRI scan was unremarkable, ruling out a demyelinating process. Serology tests (ie, ANA and dsANA) were negative. Neurology was consulted, and a lumbar puncture was performed. On HD-2 AEIM was suspected, prompting levetiracetam discontinuation and lacosamide initiation (50 mg by mouth twice daily). The CSF analysis was notable for pleocytosis (lymphocytic predominance at 96%), elevated protein (100 mg/dL), and slightly elevated glucose (79 mg/dL). The CSF VDRL was negative, ruling out neurosyphilis. Bacterial meningitis was ruled out based on the CSF analysis (WBC 144 × 103 and glucose) and the lack of bacterial growth on gram stain. Inasmuch, antibiotic therapy was not initiated. Empiric acyclovir 1000 mg IV every 8 hours was initiated as viral meningitis had not been eliminated, due to the lack of viral meningeal PCR testing. By HD-3, the CSF culture resulted without growth and the patient was alert and oriented. By HD-4 the patient was discharged, having received 6 doses of IV acyclovir, with 7 more days of oral therapy.

In 2018, McDonald et al documented the first case of probable levetiracetam-related antiepileptic induced meningitis (AEIM). The mainstay of treatment is discontinuing the offending agent. Resolution of symptoms is typically 2 to 3 days after drug discontinuation as seen in this patient case report. Symptomatic resolution within days of stopping the suspected offending drug has been observed in all reported cases of AEIM where 1 to 2 weeks is generally seen with viral meningitis. Applying the Naranjo Scale yields a score of 4, which indicates possible levetiracetam-induced meningitis in this adult patient. Providers should be cognizant when prescribing antiepileptics to assess and monitor for aseptic meningitis that may appear with atypical symptoms.

No funding

Major depressive disorder (MDD) has been ranked among the top causes worldwide of years lived with disability. In this study we assessed meaningful change for the PHQ-9 and the SDS and determined the meaningful change threshold (MCT) using anchor-based methods, which could be used to compare meaningful differences in patients within different treatment arms.

TRANSFORM-1 (NCT02417064) and -2 (NCT0241858) were Phase 3 trials that evaluated the efficacy and safety of fixed and flexible doses of esketamine nasal spray (56 mg or 84 mg) in combination with newly initiated oral antidepressant (ESK+AD) vs oral antidepressant + placebo nasal spray (AD+PBO) in TRD patients. Patient Reported Outcomes (PROs) were integrated into these trials to evaluate the patient perspective of treatment using instruments capturing concepts of importance to patients. The 9-item Patient Health Questionnaire (PHQ-9) is a PRO instrument used to assess self-reported depression symptoms and the Sheehan Disability Scale (SDS) is a PRO for self-reported function and disability. Blinded trial data (combined treatment groups) from TRANSFORM-1 was used for the anchor-based analysis. The Clinical Global Impression - Severity (CGI-S) was used as an anchor and patients were classified into response groups depending on their level of change over the course of the study. Patients were classified among all possible change categories (15 levels, ranging from -7 to 7 where negative change scores indicate improvement). Cumulative Distribution Function (CDF) curves of change from baseline to day 28 were generated using unblinded data from TRANSFORM-2 to visualize the range of responses demonstrated in the respective treatment groups for the PHQ-9 and SDS. MCT values were used to as thresholds to evaluate percentage of responders in each treatment group.

In anchor-based analyses using TRANSFORM-1 combined treatment groups, the correlation between change on the CGI-S and change on the PHQ-9 at Day 28 was high (> 0.60) with anchor-based MCTs ranging from 5 to 8 points. The magnitude of change (standardized effect size estimate within-subject change) for patients improving was exceptionally high (> 0.80). Similar results were observed on the SDS: high correlation of CGI-S and SDS at Day 28 (0.75), moderate SES (0.66), with suggested MCT ranging from 3 to 7 with an MCT value of 5 pts. CDF curves from TRANSFORM-2 showed clear separation between the ESK+AD vs AD+PBO across a number of responder definitions inclusive of those identified with the anchor-based analyses.

The current study is the first to derive an MCT on the PHQ-9 and SDS in TRD to measure meaningful change from the perspective of the patient using regulatory-preferred psychometric anchor-based methodology. These analyses assist with interpretation of meaningfulness of esketamine phase 3 clinical trial results from the patient perspective.

Study was funded by Janssen Global Services, LLC.