Neuropsychiatric Side Effects Research Articles

Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)

The COVID-19 pandemic has posed a challenge for new etiotropic agents, leading to an urgent repurposing of antimicrobial and antiviral drugs to treat a new infection based on the results of in silico, in vitro, in vivo experimental studies, and clinical trials. However, less attention has been paid to the safety of repurposed drugs. Exposure to repurposed drugs with limited risk-benefit evidence in COVID-19 required adaptation of safety monitoring, which affected the completeness and quality of reports, and making causality assessments the most difficult task. A review of data accumulated over the period of the COVID-19 pandemic on the nature of adverse reactions associated with the use of repurposed drugs (hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ribavirin) used in real practice is presented. The results of RCTs and observational studies, systematic reviews and meta-analyses were used. Systematized data on the safety of the use of hydroxychloroquine and chloroquine in patients with COVID-19 in short-term treatment (14 days), including a series of meta-analyses, the risk of adverse effects was increased by 1.52 times; the main manifestations are prolongation of the QT interval and arrhythmias (up to 25%), gastrointestinal disorders (up to 50%), increased levels of bilirubin (3%) and transaminases (up to 10%), dermatological (up to 10%) and neuropsychiatric side effects (up to 21.7%). Most of the side effects of repurposed antiviral drugs of the nucleoside analog group are associated with their direct cytotoxic effect, which is manifested by toxic damage to the gastrointestinal tract, hepatotoxicity, nephrotoxicity, cardiotoxicity, and hematotoxicity. The greatest number of side effects from the gastrointestinal tract and liver were observed for lopinavir/ritonavir in comparison with other drugs. New side effects have been identified for remdesivir when used in the context of the COVID-19 pandemic cardiotoxicity (bradycardia and severe hypotension) and nephrotoxicity, which was regarded by regulatory authorities as a safety signal. To solve the problems of assessing the cause-and-effect relationship, further more thorough research and analysis will be required. The accumulated information in the context of the ongoing COVID-19 pandemic should be subject to ongoing dynamic analysis and published in medical journals to alert clinicians.

Long-term cyclosporine A treatment promotes anxiety-like behavior: Possible relation with glutamate signaling in rat hippocampus

• Long-term CsA treatment induces anxiety-like behavior; • Hippocampus of CsA-treated rats presents increased GluN2 levels, NOS and CREB activities; • Chronic CsA administration affects hippocampal adaptive responses that can induce anxiogenic behavior. Chronic immunosuppressive treatment with cyclosporine A (CsA) leads to multiple side effects, including some that occur in the central nervous system (CNS). This study aims to investigate the impact of long-term CsA treatment on anxiety behavior and verify the alterations related to glutamate signaling in the rat hippocampus. Adult male Wistar rats were intraperitoneally injected with 15 mg/kg/day CsA for eight weeks, subjected to anxiety tests, and had their brains collected for biochemistry and Western blot analysis. Herein, we reported that eight weeks of CsA treatment promoted an anxiety-like effect and increased N-methyl-D-aspartate receptor (NMDAR) GluN2 subunit levels, nitric oxide synthase, and cAMP-response element binding protein (CREB) activities. Future work should consider the impact of long-term CsA treatment on NMDAR function, as well as on other neurotransmitter signaling pathways. Peripheral side effects should also be considered a factor that could lead to CsA-induced neuropsychiatric effects. In conclusion, this work reports modifications to CNS adaptive responses following chronic CsA treatment, which can influence anxiogenic behavior and other associated neurotoxic events. Understanding the mechanisms underlying CsA-induced neuropsychiatric side effects is an important step toward better symptom management in patients submitted to immunosuppression in the clinical setting.

Comparing the Relationships of Genetically Proxied PCSK9 Inhibition With Mood Disorders, Cognition, and Dementia Between Men and Women: A Drug-Target Mendelian Randomization Study.

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are important therapeutic options for reducing cardiovascular disease risk; however, questions remain regarding potential differences in the neuropsychiatric impact of long-term PCSK9 inhibition between men and women. Methods and Results Using PCSK9 gene single-nucleotide polymorphisms from European ancestry-based genome-wide association studies of low-density lipoprotein cholesterol (N=1 320 016), circulating PCSK9 protein levels (N=10 186), tissue-specific PCSK9 gene expression, sex-specific genome-wide association studies of anxiety, depression, cognition, insomnia, and dementia (ranging from 54 321 to 194 174), we used drug-target inverse variance-weighted Mendelian randomization (MR) and complementary MR methods (MR Egger, weighted median, and weighted mode) to investigate potential neuropsychiatric consequences of genetically proxied PCSK9 inhibition in men and women. We failed to find evidence surpassing correction for multiple comparisons of relationships between genetically proxied PCSK9 inhibition and the risk for the 12 neuropsychiatric end points in either men or women. Drug-target analyses were generally well-powered to detect effect estimates at several hypothesized thresholds for both combined-sex and sex-specific end points, especially analyses using PCSK9 instruments derived from protein and expression quantitative trait loci. Further, MR estimates across complementary MR methods and additional models using genetic instruments derived from circulating PCSK9 protein levels and tissue-specific PCSK9 expression were in alignment, strengthening causal inference. Conclusions Genetically proxied PCSK9 inhibition showed a neutral neuropsychiatric side effect profile with no major sex-specific differences. Given statistical power considerations, replication with larger samples, as well as data from other ancestral populations, are necessary. These findings may have important clinical implications for lipid-lowering drug-prescribing practices and side effect monitoring of approved and future PCSK9 therapies.

Recent Updates on the Development of Deuterium-Containing Drugs for the Treatment of Cancer.

Cancer is one of the deadliest diseases in the world. In 2020, 19.3 million cancer cases and 10 million deaths were reported in the world. It is supposed that the prevalence of cancer cases will rise to 28.4 million by 2040. Chemotherapy-based regimens have a narrow therapeutic index, severe adverse drug reactions, and lack metabolic stability. Besides, the metabolism of anticancer produces several non-active and toxic metabolites that reduce exposure of the target site to the parent drug. Therefore, developing better-tolerated and effective new anticancer drugs and modification of the existing anticancer drugs to minimize toxicity and increase efficacy has become a very urgent need. Deuterium incorporation reduces the metabolism of certain drugs that are breakdown by pathways involving hydrogen-carbon bond scission. For example, CYP450 mediated oxidative metabolism of drugs that involves the breakdown of a hydrogen-carbon bond affected by deuteration. Deuterium incorporation into the drug increases the half-life and reduces the dose, which provides better safety and efficacy. Deutetrabenazine is the first deuterated form of tetrabenazine approved to treat chorea associated with Huntington’s disease and tardive dyskinesia. The study revealed that Deutetrabenazine has fewer neuropsychiatric side effects with favorable safety than tetrabenazine. The current review highlights the deuterium kinetic isotope effect on drug metabolism, deuterated compound pharmacokinetic property, and safety profile. Besides, this review explains the deuterated anticancer drug development update status.

POST-STROKE DEPRESSION AMONG STROKE SURVIVORS ATTENDING THERAPY CENTERS IN CHITWAN

Background: The neuropsychiatric side effect of post-stroke depression is one of the most prevalent in stroke survivors. The purpose of this study was to determine the extent of post-stroke depression and the factors that influence post-stroke depression among stroke survivors attending therapy centers at various hospitals in Chitwan. Methods: A hospital-based cross-sectional study using the face-to-face interview method was carried out in different therapy centers in Chitwan, Nepal. A total of 137 stroke survivors were considered as a sample. The data was collected from November 25, 2021 to January 29, 2021. We used Pearson’s Chi-square test and binary logistic regression analysis to assess the factors influencing post-stroke depression among stroke survivors in Chitwan. Results: Among 137 stroke survivors, just more than half i.e., 54.70% (75) suffered from any kind of depression, and the remaining participants i.e. 45.30% (62) did not have depression. Result showed that current depression status among stroke survivors were significantly associated with age group [above 60 years (COR =2.88; CI=1.17-7.10)], educational status [primary and below (COR =4.02; CI=1.47-10.95)], past employment status [unemployment (COR=2.79; CI=1.37-5.69)], past alcohol intake [alcohol intake (COR=1.04; CI=0.52-2.10)] and current BMI status [underweight (COR =1.23; CI=0.24-6.07)]. Conclusions: More than half, or 54.70% (75), suffered from depression, which is an unacceptable rate. Increased literacy, improved socioeconomic status, and lifestyle changes among stroke survivors would reduce the severity of depression. It is necessary to provide comprehensive, up-to-date information as well as supportive interventions with the goal of reducing depression among stroke survivors.

Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK Biobank

ObjectiveTo test the hypothesis that systemic and inhaled glucocorticoid use is associated with changes in grey matter volume (GMV) and white matter microstructure.DesignCross-sectional study.SettingUK Biobank, a prospective population-based cohort study...

The association between cardiac drug therapy and anxiety among cardiac patients: results from the national DenHeart survey

BackgroundNeuropsychiatric side effects of cardiac drugs such as nervousness, mood swings and agitation may be misinterpreted as symptoms of anxiety. Anxiety in cardiac patients is highly prevalent and associated with poor outcomes, thus an accurate identification is essential. The objectives were to: (I) describe the possible neuropsychiatric side effects of common cardiac drug therapies, (II) describe the use of cardiac drug therapy in cardiac patients with self-reported symptoms of anxiety compared to those with no symptoms of anxiety, and (III) investigate the association between the use of cardiac drug therapy and self-reported symptoms of anxiety.MethodsDenHeart is a large national cross-sectional survey combined with national register data. Symptoms of anxiety were measured by the Hospital Anxiety and Depression Scale (HADS-A) on patients with ischemic heart disease, arrhythmia, heart failure and heart valve disease. Side effects were obtained from ‘product summaries’, and data on redeemed prescriptions obtained from the Danish National Prescription Registry. Multivariate logistic regression analyses explored the association between cardiac drug therapies and symptoms of anxiety (HADS-A ≥ 8).ResultsAmong 8998 respondents 2891 (32%) reported symptoms of anxiety (HADS-A ≥ 8). Neuropsychiatric side effects were reported from digoxin, antiarrhythmics, beta-blockers, ACE-inhibitors and angiotensin receptor antagonists. Statistically significant higher odds of reporting HADS ≥ 8 was found in users of diuretics, lipid-lowering agents, nitrates, antiarrhythmics and beta-blockers compared to patients with no prescription.ConclusionSome cardiac drugs were associated with self-reported symptoms of anxiety among patients with cardiac disease. Of these drugs neuropsychiatric side effects were only reported for antiarrhythmics and beta-blockers. Increased awareness about the possible adverse effects from these drugs are important.

The effects of AVM0703 mobilization of endogenous gamma delta/invariant TCR+ bispecific natural killer T-like cells against solid tumors and blood cancers.

2579 Background: Glucocorticoids (GC) are a common component of blood cancer regimens, typically at doses 40 mg or lower due to concerns of pancreatitis and hepatotoxicity (Walasik-Szemplińska et al. Thyroid Research. 2019;12:13; Ataallah et al. Cureus. 2020;12[7]) and neuropsychiatric effects. AVM Biotechnology has developed a high concentration, high volume, preservative-free, patent pending formulation of dexamethasone (AVM0703), that allows administration of up to 21 mg/kg (1470 mg for 70 kg) over a one-hour IV infusion. Prophylactic use of circadian physiologic hydrocortisone reduces the risk of GC neuropsychiatric side-effects (Warris LT, et al. J. Clin. Oncol. 2016;34:2287; Meijer & de Kloet Endocrinology. 2017;158:448). Acute supra-pharmacologic doses (>6 mg/kg) AVM0703 mobilizes endogenous bispecific gamma delta invariant TCR+ bi-specific Natural Killer T-like cells (AVM-NKT) (PCT/US21/19773), via a non-GC receptor, that rapidly home to diseased organs in preclinical models and are directly related to tumor killing, including Non-Hodgkin’s Lymphoma, Melanoma, and Multiple Myeloma. Methods: Cancer cell lines and (mouse host) were i) immune-resistant mouse A20 B lymphoma (Balb/c), ii) xenografted human T-ALL CCRF-CEM (NCRnu), iii) mouse B16F10 melanoma (B62DF1), and iv) mouse MOPC315 (Balb/c). Cancer cell lines were inoculated into the flank either as single cell suspensions or encased in Matrigel. When tumor volume reached between 100-500mm3 well-established tumors, mice were orally gavaged with a human equivalent dose (HED) of 15-18 mg/kg AVM0703 as monotherapy, or as a preconditioning prior to adoptive cell transfer (ACT), or in combination with chemotherapy. Responses were determined by tumor volume measurements, tumor immunohistochemistry or flow cytometry detection of residual cancer cells. Results: Immunohistochemistry analysis of tumors from AVM0703 treated mice demonstrated pseudoprogression similar to checkpoint inhibitors: i.e. tumors were measurable however in some cases all cancer cells had been eradicated. Therefore, subsequent tumor monitoring at end point was done by flow cytometry to quantify the total number of live cancer cells more accurately than tumor measurements by calipers or immunohistochemistry, due to pseudoprogression and limitations of examining only a few sections from each tumor. Conclusions: AVM0703 led to: i) complete response (CR) in 27% of immune-resistant mouse A20 tumors as monotherapy and CR in 60% when combined with 2 doses of cyclophosphamide/fludarabine (CyFlu); ii) tumor eradication and long-term memory against xenografted human T-ALL; iii) enhancement of ACT equivalent to CyFlu preconditioning in mouse melanoma; and iv) preliminary 95% CR against mouse multiple myeloma.

The mobilization of endogenous bi-specific natural killer T-like cells and independent of glucocorticoid receptor activation related to acute supra-pharmacologic weight-based dexamethasone (AVM0703) and 18 mgs/kg body weight.

e14545 Background: Glucocorticoids (GC) are a common component of blood cancer regimens, at doses 40 mg or lower due to concerns of pancreatitis and hepatotoxicity (Walasik-Szemplińska et al. Thyroid Research (2019) 12:13; Ataallah et al. Cureus. 2020 Jul; 12(7)) and neuropsychiatric effects. AVM Biotechnology has developed a high concentration, high volume, preservative-free, patent pending formulation of dexamethasone (Dex) (AVM0703), allowing administration up to 21 mg/kg (1470 mg for 70 kg) in one-hour IV infusion. Prophylactic use of physiologic hydrocortisone reduces the risk of GC neuropsychiatric side-effects (Warris, L. T. et al. J. Clin. Oncol. (2016) 34:2287; Meijer & de Kloet Endocrinology (2017) 158:448). At supra-pharmacologic doses (>6 mg/kg) AVM0703 mobilizes endogenous bispecific gamma delta invariant TCR+ Natural Killer T-like cells (AVM-NKT) (PCT/US21/19773), via a non-GC receptor, that rapidly home to cancer in tumor models and are directly related to tumor killing. GCs have been reported to induce biological responses independent of GCRs: corticosterone has been shown to bind a G-protein coupled receptor that does not bind either Dex or aldosterone (Mitre-Aguilar, et. Al International Journal of Clinical and Experimental Pathology (2015) 8:1; Powell, C. E., et. Al. Endocrine (1999) 10: 271) and the non-GCR mineralocorticoid receptor has high affinity for prednisone but not Dex. Methods: a) Mouse splenocytes or human whole blood were incubated with Dex from 1nM to 1mM. Apoptosis was measured for human whole blood by CBCs and for mouse splenocytes by flow cytometry 4 to 6 hours later. RU486 was used to block expected transmembrane (tm)GCR activity. b) Naïve, tumor bearing and humanized mice were dosed with AVM0703 at human equivalent doses (HED) >18 mg/kg. Depending on the disease state of the mice, novel AVM-NKT were observed in the blood between 3 and 96 hours later, determined by flow cytometry. Results: a) Apoptosis via the tmGCR was observed at expected concentrations between 10nM and 100uM and was blocked by the GCR antagonist RU486. At concentrations above 250uM, which correspond to in vivo peak blood levels from acute 7mg/kg and greater, no Dex-induced apoptosis was observed. b) Acute supra-pharmacologic AVM0703 induced the appearance of CD3+, CD56+, gdTCR+, invariant TCR+ bi-specific Natural Killer T-like cells, that in a cancer setting also expressed activation markers like CD16 and NKp44. Intriguingly, the AVM-NKT also express B220 in certain settings, and CD3+ B220+ DP has been indicative of IL-2 or IL-12 lymphoma killing (Masztalerz, A, et. Al. Anticancer Res (2004) 24(5A):2633). Conclusions: CBC’s and clinical chemistries from enrolling clinical trial confirmed the in vitro non-GCR findings.

Prescription Patterns of Asthma Preventers Among Children and Adolescents Between Australia and South Korea.

Purpose: Inhaled Corticosteroids (ICSs) and oral Leukotriene Receptor Antagonists (LTRAs) are commonly prescribed asthma preventers, however, concerns have been raised as to whether montelukast (LTRA) is associated with an increase in occurrences of neuropsychiatric side effects in children. Our study was conducted to observe prescribing patterns of asthma preventers among paediatric patients specifically focusing on ICSs and LTRAs between Australia and South Korea to see intercountry differences in the use of these medicines. Materials and Methods: The Health Insurance Review and Assessment Paediatric Patients Sample dataset for South Korea and data provided by Services Australia were used in the study. Paediatric patients aged between 3 and 19 with more than one dispensing of an asthma preventer and at least one reliever between 1 Jan 2018 and 31 December 2018 were selected. Prevalence per 1,00,000 persons and standardised prevalence were estimated. Results: A total of 3,58,470 patients (2,04,270 from South Korea and 1,54,200 from Australia) were included in the study. A higher prevalence of ICS-based inhalers was seen in Australia with 80.1% compared to 13.5% in South Korea. In addition, Australia showed a stronger tendency of prescribing high dose ICS-based inhalers compared to South Korea with 22.9% vs. 4.9%. In contrast, use of LTRAs was more prevalent in South Korea with 57.6% while in Australia, montelukast was the only LTRA dispensed at a proportion of 18.9%. Moreover, 29.9% of xanthines which are orally available preventers, were prescribed more frequently in South Korea compared to Australia (0.1%). Conclusion: Australia showed a tendency of prescribing ICS-based preventers whereas South Korea exhibited a preference towards the oral LTRAs. Given the potential risk of neuropsychiatric side effects among paediatric patients with montelukast, reasons for the high use of montelukast in South Korea should be investigated further.

Functional connectivity maps of theta/alpha and beta coherence within the subthalamic nucleus region

The subthalamic nucleus (STN) is a primary target for deep brain stimulation in Parkinson's disease (PD). Although small in size, the STN is commonly partitioned into sensorimotor, cognitive/associative, and limbic subregions based on its structural connectivity profile to cortical areas. We investigated whether such a regional specialization is also supported by functional connectivity between local field potential recordings and simultaneous magnetoencephalography. Using a novel data set of 21 PD patients, we replicated previously reported cortico-STN coherence networks in the theta/alpha and beta frequency ranges, and looked for the spatial distribution of these networks within the STN region. Although theta/alpha and beta coherence peaks were both observed in on-medication recordings from electrode contacts at several locations within and around the STN, sites with theta/alpha coherence peaks were situated at significantly more inferior MNI coordinates than beta coherence peaks. Sites with only theta/alpha coherence peaks, i.e. without distinct beta coherence, were mostly located near the border of sensorimotor and cognitive/associative subregions as defined by a tractography-based atlas of the STN. Peak coherence values were largely unaltered by the medication state of the subject, however, theta/alpha peaks were more often identified in recordings obtained after administration of dopaminergic medication. Our findings suggest the existence of a frequency-specific topography of cortico-STN coherence within the STN, albeit with considerable spatial overlap between functional networks. Consequently, optimization of deep brain stimulation targeting might remain a trade-off between alleviating motor symptoms and avoiding adverse neuropsychiatric side effects.

Clinical pattern of synthetic cannabinoids users in Upper Egypt: cross-sectional study

BackgroundThere is an expanding use of new psychoactive substances containing synthetic cannabinoids in the last years. This study was conducted to identify the epidemiologic data of acute and chronic toxicity by synthetic cannabinoids in Upper Egypt patients.ResultsAll cases included in the presenting study were fifty males. Most users of synthetic cannabinoids were in the adolescence and middle age group (15–< 35) representing 68%. Curiosity was the most common motivator for using synthetic cannabinoids. Alteration of perception was reported in 68% of subjects after synthetic cannabinoids use. Additionally, dizziness, loss of consciousness, convulsion, and panic attacks were also reported. Cardiovascular adverse effects experienced by users were palpitations (76%) and chest pain (12%). Half of included subjects (50%) reported financial problems and about one-third (32%) got involved in domestic violence. Abnormal routine laboratory findings that were found in included cases were in the form of 12% anemia, 10% leukocytosis, and 6% leucopenia. Also, liver and kidney functions were elevated in 8% and 4% of the cases, respectively. While 22% and 4% of cases were positive for hepatitis C and HIV respectively.ConclusionsThis study can be concluded that adolescence are the most common users of SCs; neuro-psychiatric and cardiovascular side effects were the most experienced by subjects. Violence in many forms, especially domestic violence, was associated with synthetic cannabinoids abuse.Trial registrationRegistered in clinical trial under name syntheticcannabinoidsAssiut and ID NCT03866941 and URL.

Case study: New onset of neuropsychiatric symptoms following switching to a dolutegravir regimen

Although reports of neuropsychiatric side effects have been reported with efavirenz, these have been limited in comparison with regard to the now recommended dolutegravir regimens. We present a patient with new onset neuropsychiatric manifestations secondary to dolutegravir that resulted in significant physical injuries. The patient was initiated on risperidone for symptomatic control which was subsequently weaned and discontinued following reverting to an original efavirenz antiretroviral regimen, with resolution of neuropsychiatric symptoms. Neuropsychiatric side effects are increasingly noted with dolutegravir, and these should be monitored for on initiation and switching of treatment regimens.

Psychosis beas\xa0 a rare side effect of sildenafil: a\xa0case report

BackgroundSildenafil citrate is a commonly used medication for the management of erectile dysfunction. Previous studies have described some neuropsychiatric side effects of this medication. So far, however, there has been little discussion about sildenafil-induced psychosis.Case presentationWe here present the case of a 32-year-old Iranian male, without a known psychiatric history, who developed psychotic symptoms following initiation of sildenafil. We also postulate a mechanism by which this may occur.ConclusionsThis report highlights the importance of watchful observation for the occurrence of this rare but serious side effect. Further studies are needed to clarify the precise mechanism that causes sildenafil-induced psychosis.

Assessment of Repetitive and Compulsive Behaviors Induced by Pramipexole in Rats: Effect of Alpha-Synuclein-Induced Nigrostriatal Degeneration.

Treatment with dopamine agonists in Parkinson’s disease (PD) is associated with debilitating neuropsychiatric side-effects characterized by impulsive and compulsive behaviors. The vulnerability to develop such impairments is thought to involve interactions between individual vulnerability traits, types of antiparkinsonian medications, and the neurodegenerative process. We investigated the effect of the dopamine D3/D2 agonist pramipexole (PPX) and selective nigrostriatal degeneration achieved by viral-mediated expression of alpha-synuclein on the expression of repetitive and compulsive-like behaviors in rats. In a task assessing spontaneous food hoarding behavior, PPX increased the time spent interacting with food pellets at the expense of hoarding. This disruption of hoarding behavior was identical in sham and lesioned rats. In an operant post-training signal attenuation task, the combination of nigrostriatal lesion and PPX decreased the number of completed trials and increased the number of uncompleted trials. The lesion led to an increased compulsive behavior after signal attenuation, and PPX shifted the overall behavioral output towards an increased proportion of compulsive lever-presses. Given the magnitude of the behavioral effects and the lack of strong interaction between PPX and nigral degeneration, these results suggest that extra-nigral pathology may be critical to increase the vulnerability to develop compulsive behaviors following treatment with D3/D2 agonists.

Epilepsy in adults with neurodevelopmental disability - what every neurologist should know.

This seminar in epileptology addresses Learning Objective 6.1.4 of the International League against Epilepsy Curriculum: Demonstrate the ability to recognize and manage the special needs of persons with epilepsy (and Neurodevelopmental Disorders [NDDs]). The review identifies the essential competencies for neurologists working with people with epilepsy and NDDs, and these competencies are discussed alongside clinical examples. Furthermore, the seminar explores the opportunities offered by integrated service provision between neurology and services for NDD. The epileptic encephalopathies are not a subject of this seminar paper as they are circumscribed by other ILAE learning objectives. This seminar frames the complexity of seizures in association with NDD with a focus on major NDDs; intellectual disability, autism spectrum disorder, and attention deficit hyperactivity disorder. The evidence presented considers epidemiology, co-morbidities, risk factors, mortality, and the diagnostic and treatment challenges. People with NDDs and epilepsy have higher rates of physical and psychiatric co-morbidity, polypharmacy, neuropsychiatric side effects of drugs, and premature mortality including sudden unexpected death in epilepsy. There is a limited Level 1 evidence base to guide assessment and treatment for seizures in adults with NDDs. Therefore, throughout this seminar, the evidence presented for associations and treatment should be observed in context along with its limitations. The evidence for pharmacological treatment of seizures in association with NDDs is presented alongside expert commentary and guidance. There is Level 2 evidence to support treatment with some of the newer anti-seizure medications including brivaracetam, lacosamide, eslicarbazepine acetate, and perampanel as second-line choices. Seizures with a co-morbid NDD should be considered as a collective complex clinical presentation and not discrete conditions. This seminar was co-designed, co-produced and co-authored by an expert by experience and includes case studies and a video to highlight what can go wrong and how it can be avoided.

Depressive symptoms are no longer a barrier to HCV treatment initiation in the HIV–HCV co-infected population in Canada

Background Psychiatric illness was a major barrier for HCV treatment during the Interferon (IFN) treatment era due to neuropsychiatric side effects. While direct acting antivirals (DAA) are better tolerated, patient-level barriers persist. We aimed to assess the effect of depressive symptoms on time to HCV treatment initiation among HIV–HCV co-infected persons during the IFN (2003–2011) and second-generation DAA (2013–2020) eras. Methods We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). We predicted Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) classes for depressive symptoms indicative of a depression risk using a random forest classifier and corrected for misclassification using predictive value-based record-level correction. We used marginal structural Cox proportional hazards models with inverse weighting for competing risks (death) to assess the effect of depressive symptoms on treatment initiation among HCV RNA-positive participants. Results We included 590 and 1127 participants in the IFN and DAA eras. The treatment initiation rate increased from 9 (95% confidence interval (CI): 7–10) to 21 (95% CI: 19–22) per 100 person-years from the IFN to DAA era. Treatment initiation was lower among those with depressive symptoms compared to those without in the IFN era (hazard ratio: 0.81 (95% CI: 0.69–0.95)) and was higher in the DAA era (1.19 (95% CI: 1.10–1.27)). Conclusion Depressive symptoms no longer appear to be a barrier to HCV treatment initiation in the co-infected population in the DAA era. The higher rate of treatment initiation in individuals with depressive symptoms suggests those previously unable to tolerate IFN are now accessing treatment.

Levetiracetam Prophylaxis Therapy for Brain Tumor-Related Epilepsy (BTRE) Is Associated With a Higher Psychiatric Burden

Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis.Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up.Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed.Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM.

Management of Medication-Induced Psychiatric Disorders.

Management of Medication-Induced Psychiatric Disorders.

Clinical considerations with use of psychotropic medications in COVID-19 patients

Clinical considerations with use of psychotropic medications in COVID-19 patients