Neuropsychiatric Adverse Events Research Articles

Assessing the Incidence Rate of Neuropsychiatric Adverse Effects in Older Adults Following Levetiracetam Initiation: A Retrospective Study.

Levetiracetam (LEV) is commonly prescribed for epilepsy management. However, neuropsychiatric disorders (NPDs) are concerning adverse effects that may result in medication discontinuation. This study aims to examine the incidence and factors influencing LEV associated NPDs in adult patients aged 50 years and above. A retrospective analysis was conducted on patients aged 50 years and above prescribed LEV between 2010 and 2020, with at least one follow-up appointment six months post-treatment initiation. The incidence of new-onset or aggravated NPDs and variables potentially influencing this risk were examined. Independent t-test, chi-squared, and Fisher's exact test were used, in addition to univariate and multivariate logistic regression. The study included 100 patients with a mean age at LEV start of 63.31 years (SD = 16.48). Neuropsychiatric symptoms were observed in 6 (6.0%) patients. Factors associated with new-onset NPDs were younger age at epilepsy diagnosis (p=0.005), younger age at LEV start (p=0.004), and concurrent use of Carbamazepine/Oxcarbazepine (p=0.004). On multivariate analysis, only the association with Carbamazepine/Oxcarbazepine remained significant (OR 14.62, 95% CI 1.86-114.70, p=0.011). The findings indicate that the incidence of NPDs in elderly patients is relatively low (6%). Further research with larger samples is needed in comparison with a younger sample as a control group to confirm these findings.

Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial

ObjectiveTo determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression.DesignRandomised, double blind, placebo controlled trial with two parallel arms.SettingFive tertiary...

The Use of Neuraminidase Inhibitors in Teenagers May Not Increase the Risk of Neuropsychiatric Adverse Events: A Nationwide Population-based Retrospective Study

Abstract Background: Pandemic influenza virus is a public health issue, and the neuraminidase inhibitors (NIs) “Oseltamivir” and “Zanamivir” are effective treatments. While teenagers use NIs, there are concerns regarding neuropsychiatric adverse events (NPAEs). Aim: We aimed to use the Taiwan National Health Insurance Research Database to identify the correlation between NPAEs and NIs use in teenagers aged 13–19 years. Methods: The final population between 2000 and 2015 included in this study was 3698 individuals, with 2287 individuals having received “Oseltamivir” and “Zanamivir” (study cohort group) and 9148 individuals not receiving “Oseltamivir” and “Zanamivir” (comparison cohort group). We initially used a multivariate Cox regression analysis during the tracking period to determine the cumulative incidence of NPAEs. Results: Our findings revealed no significant increase in the likelihood of developing NPAEs in the study group. The Kaplan–Meier survival curve demonstrated that individuals who received “Oseltamivir” and “Zanamivir” were not associated with statistically significantly increased NPAEs compared with controls (log-rank test, P = 0.724). Conclusion: No more risk in comparison of the normal population in our study, and the safety of “Oseltamivir” and “Zanamivir” is established treatments for influenza.

Neuropsychiatric effects of glucocorticoids

Neuropsychiatric effects of glucocorticoids

A Bayesian approach for investigating the pharmacogenetics of combination antiretroviral therapy in people with HIV.

Combination antiretroviral therapy (ART) with at least three different drugs has become the standard of care for people with HIV (PWH) due to its exceptional effectiveness in viral suppression. However, many ART drugs have been reported to associate with neuropsychiatric adverse effects including depression, especially when certain genetic polymorphisms exist. Pharmacogenetics is an important consideration for administering combination ART as it may influence drug efficacy and increase risk for neuropsychiatric conditions. Large-scale longitudinal HIV databases provide researchers opportunities to investigate the pharmacogenetics of combination ART in a data-driven manner. However, with more than 30 FDA-approved ART drugs, the interplay between the large number of possible ART drug combinations and genetic polymorphisms imposes statistical modeling challenges. We develop a Bayesian approach to examine the longitudinal effects of combination ART and their interactions with genetic polymorphisms on depressive symptoms in PWH. The proposed method utilizes a Gaussian process with a composite kernel function to capture the longitudinal combination ART effects by directly incorporating individuals' treatment histories, and a Bayesian classification and regression tree to account for individual heterogeneity. Through both simulation studies and an application to a dataset from the Women's Interagency HIV Study, we demonstrate the clinical utility of the proposed approach in investigating the pharmacogenetics of combination ART and assisting physicians to make effective individualized treatment decisions that can improve health outcomes for PWH.

APOE-ε4 allele[s]-associated adverse events reported from placebo arm in clinical trials for Alzheimer's disease: implications for anti-amyloid beta therapy

APOE-ε4 allele[s] is a risk factor for Alzheimer's disease (AD) and Amyloid-Related Imaging Abnormalities (ARIA) in anti-amyloid beta therapy, and is also associated with cerebrovascular risk factors such as hyperlipidemia or atherosclerosis. During AD clinical trials, APOE-ε4 carriers may experience neuropsychiatric adverse events (AEs) related to these risks, complicating the differentiation of ARIA from cerebrovascular events based on symptoms. This study aimed to examine the hypothetical impact of considering the APOE-ε4 allele's risk for non-ARIA AEs during AD clinical trials. We used data from the Critical Path for Alzheimer's Disease (CPAD) from the placebo arm of randomized controlled trials (RCT) for AD treatment. We determined whether AEs were reported more frequently in APOE-ε4 carriers, quantifying with reporting odds ratio (ROR) using a mixed effect model. We also evaluated the association between ROR levels and the prior probability that an AE is symptomatic ARIA. We analyzed 6,313 patients with AD or mild cognitive impairment in 28 trials. Of the prespecified 35 neuropsychiatric or related AEs, several had a significantly high ROR: “delusion” (ROR = 4.133), “confusional state” (ROR = 1.419), “muscle spasms” (ROR = 9.849), “irritability” (ROR = 12.62), “sleep disorder” (ROR = 2.944), or “convulsion” (ROR = 13.00). However, none remained significant after adjusting for Mini-Mental State Examination scores. There is no strong evidence to suggest that specific neuropsychiatric AEs occur more frequently without drug treatment association among APOE-ε4 carriers. The influence of APOE-ε4 allele[s] on the clinicians' assessment of the likelihood of ARIA during safety monitoring in anti-amyloid beta monoclonal antibody treatment might be unchanged, thus maintaining the current level of awareness of clinicians of AEs.

ADR assessment of isoniazid induced psychosis: Case report and review of literature

Tuberculosis ranks among the top 10 causes of death globally and stands as the primary cause attributed to a single infectious agent. Among all antitubercular drugs, Isoniazid is most important role in the management of pulmonary tuberculosis.Various neuropsychiatric adverse effects have been documented in association with the use of isoniazid, both in therapeutic and overdose scenarios. This case report describes a 68-year-old male with multiple health issues, including disseminated tuberculosis, developed drug-induced psychosis, likely due to isoniazid in his anti-tubercular therapy. This case underscores the challenges of psychiatric adverse effects in tuberculosis treatment and emphasizes the importance of prompt recognition and intervention.

Incidence and determinants of adverse events in individuals with HIV commencing Dolutegravir-based antiretroviral therapy in mainland Tanzania

Tanzania adopted a Dolutegravir (DTG)-based regimen as first-line treatment in 2019 following the World Health Organization recommendation. Data on the DTG safety profile from sub-Saharan Africa including Tanzania are limited. We investigated the incidence of DTG-related adverse events (AEs) and associated factors among people living with HIV (PLHIV) initiated on a DTG regimen. A prospective cohort study was conducted from 25 Care and Treatment Clinics in mainland Tanzania. PLHIV aged 12 years and above who were initiated on a DTG-based regimen were actively followed up for three months. The Cox regression model was used to determine the predictors of occurrence of AEs over time. A p-value of 0.05 was considered statistically significant. From January 2020 to June 2022, a cohort of 935 participants who were both newly diagnosed and ART-experienced who transitioned to a DTG-based regimen was enrolled. Out of 935 participants, 59 (6.3%) reported a total of 62 AEs. The most frequently experienced AE was skin itching and rashes (15/62; 24.2%). DTG-associated neuropsychiatric AEs were less common and included headache (6 [9.6%]) and sleep disturbances (3 [4.8%]). The overall incidence of occurrence of the first AEs was 96.7 per 1000 person-months [95% C.I: 74.4–125.7] with the highest incidence observed among the elderly (≥ 60 years). Individuals on WHO HIV Clinical Stage 2 had a 2.7 significantly higher risk of developing AEs (adjusted hazard ratio = 2.73, 95% CI = 1.46–5.12, p = 0.017). We report a low incidence of grade I (mild) and grade II (moderate) DTG-associated AEs suggesting that the regimen is generally safe in the population. Continued monitoring of DTG safety in the population is recommended.

Paranoid psychosis after a single parenteral dose of indomethacin administered for headache diagnosis: A case and review of the literature

Background: Indomethacin is a non-steroidal anti-inflammatory used to diagnose and treat hemicrania continua and paroxysmal hemicrania. Treatment can be complicated by gastrointestinal adverse effects; less commonly reported are idiosyncratic neuropsychiatric adverse effects with indomethacin. Methods: A 50-year-old male with lateralized brief attacks of headache associated with cranial autonomic symptoms was administered a single 200 mg dose of intramuscular indomethacin. Within an hour, he developed acute psychosis, with paranoid delusions and verbal and physical aggression lasting 5 h, followed by recovery to baseline. We used search terms “indomethacin psychosis,” “indomethacin psychiatric,” “indomethacin side effects,” “non-steroidal anti-inflammatory psychosis,” and “non-steroidal anti-inflammatory psychiatric” within PubMed to identify previous reports and literature in this area. Results: Neuropsychiatric adverse effects of indomethacin have been reported since 1965 in a dose-dependent manner, usually with oral courses. They may be more common in the elderly, postpartum women and postoperative patients. Conclusion: Neuropsychiatric adverse effects should be considered in headache medicine, particularly in at-risk groups when indomethacin is administered. Patients, particularly those at highest risk, should be counseled about the risk of neuropsychiatric side effects on indomethacin which may be dose-dependent and are generally reversible on stopping the drug.

Assessing the risk of intentional self-harm in montelukast users: an updated Sentinel System analysis using ICD-10 coding

Background Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS). Methods Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps. Results Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses. Conclusion Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.

Neuropsychiatric Adverse Effects of Synthetic Glucocorticoids: A Systematic Review and Meta-Analysis.

Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids. Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model. We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use. The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.

Steroid-induced Psychosis in a Patient without a Previous Psychiatric History

This is a 45-year-old Hispanic male with retinitis pigmentosa, no previous psychiatric history, and no known substance use disorder who was treated with 80 mg of oral prednisone, tapered off over 6 weeks before undergoing eye surgery. One week after completing the treatment, he went missing, and when he was found, he described visual and auditory hallucinations, as well as paranoid thoughts. He demonstrated a calm affect, flat mood, decreased expressiveness, poor eye contact, and fluent speech. The thought process was linear and goal-directed. Thought content was negative for hallucinations and paranoia, but delusional, with limited judgment and insight into his current situation. Negative suicidal or homicidal ideations. He was admitted to the hospital for further work up for encephalopathy. Images and laboratory results were irrelevant. The patient's encephalopathy completely resolved the following day, and no antipsychotic medications were administered. The psychiatric assessment was compatible with steroid-induced psychosis based on the acute onset, the brief psychotic episode with complete resolution of symptoms (5 days), precipitated by stressors (combined effects of an incapacitating disease). With this case presentation, we want to raise awareness among primary care physicians of the occurrence of steroid-induced psychosis and highlight the importance of patient education including their caregivers, as the cornerstone for an early recognition and prompt management of neuropsychiatric adverse events of glucocorticosteroids.

Immunotherapeutic treatment of inflammation in mice exposed to methamphetamine.

Currently, there are no FDA-approved medications to treat methamphetamine addiction, including the inflammatory, neurotoxic, and adverse neuropsychiatric effects. We have shown that partial (p)MHC class II constructs (i.e., Recombinant T-cell receptor Ligand - RTL1000), comprised of the extracellular α1 and β1 domains of MHC class II molecules linked covalently to myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide, can address the neuroimmune effects of methamphetamine addiction through its ability to bind to and down-regulate CD74 expression, block macrophage migration inhibitory factor (MIF) signaling, and reduce levels of pro-inflammatory chemokine ligand 2 (CCL2). The present study evaluated the effects of our third-generation pMHC II construct, DRmQ, on cognitive function and concentration of inflammatory cytokines in the frontal cortex, a region critical for cognitive functions such as memory, impulse control, and problem solving. Female and male C57BL/6J mice were exposed to methamphetamine (or saline) via subcutaneous (s.c.) injections administered four times per day every other day for 14 days. Following methamphetamine exposure, mice received immunotherapy (DRmQ or ibudilast) or vehicle s.c. injections daily for five days. Cognitive function was assessed using the novel object recognition test (NORT). To evaluate the effects of immunotherapy on inflammation in the frontal cortex, multiplex immunoassays were conducted. ANOVA was used to compare exploration times on the NORT and immune factor concentrations. Post hoc analysis revealed increased novel object exploration time in MA-DRmQ treated mice, as compared to MA-VEH treated mice (non-significant trend). One-way ANOVA detected a significant difference across the groups in the concentration of macrophage inflammatory protein-2 (MIP-2) (p = 0.03). Post hoc tests indicated that mice treated with methamphetamine and DRmQ or ibudilast had significantly lower levels of MIP-2 in frontal cortex, as compared to mice treated with methamphetamine and vehicle (p > 0.05). By specifically targeting CD74, our DRQ constructs can block the signaling of MIF, inhibiting the downstream signaling and pro-inflammatory effects that contribute to and perpetuate methamphetamine addiction.

Meta-analysis of the relationship between montelukast use and neuropsychiatric events in patients with allergic airway disease

Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses verifying this relationship remain lacking. To better understand the relationship between montelukast and neuropsychiatric events, it is vital to guide patients in the effective use of the drug, especially in children whose mothers are concerned about its side effects. In this study, randomized controlled trials (RCTs) investigating montelukast and neuropsychiatric events were retrieved from a literature search of the Medline (1966 to February 2023), Embase (1974 to February 2023), Web of Science, and other related databases. After screening, 18 RCTs were ultimately included in a meta-analysis to merge statistics, which demonstrated no significant increase in neuropsychiatric events compared with placebo. A similar pattern of adverse neuropsychiatric events was observed in patients grouped according to age, with headache being the most common adverse neuropsychiatric event. Overall, montelukast did not significantly increase neuropsychiatric events in patients with allergic rhinitis and/or asthma compared with placebo. Large-sample RCTs are needed to verify the association between neuropsychiatric events and montelukast use in children, and attention is also devoted to FDA warnings.

Combining varenicline preloading with Acceptance and Commitment Therapy (ACT) in persons with serious mental illness who smoke: The randomized ACTSLow pilot feasibility trial

BackgroundPeople with serious mental illness (SMI; bipolar [BD] or schizophrenia spectrum disorders [SSD]) who smoke have 30–60% lower odds of quitting and are more prone to experience neuropsychiatric adverse events (NPSAEs) when quitting than smokers without SMI. We pilot-tested the feasibility of combining two different dosing strategies of varenicline preloading with Acceptance and Commitment Therapy (ACT) in persons with SMI in an attempt to bolster quit rates without increasing NPSAEs. MethodsTwelve-week, single center, randomized, double-blind, pilot feasibility trial of low (0.5mg twice daily, slower titration) versus standard dose (1.0mg twice daily, standard titration) varenicline in persons with BD or SSD with a 12-week follow-up. All participants received up to 10 sessions of ACT for smoking cessation. Participants were asked to preload with varenicline while still smoking and set a flexible target quit day (TQD) by day 35. ResultsRecruitment was hampered by shutdowns related to COVID-19 and the worldwide varenicline recall, respectively. Retention goals were met. Treatment satisfaction was high across both dosing and diagnostic groups. Most participants (92.9%) adhered to preloading instructions and the flexible TQD. Seven-day point prevalence abstinence at week 12 was highest in BD participants (37.5%) but lowest in SSD participants (16.7%) who received the standard dose. Medication was well tolerated. ConclusionsAlthough recruitment was hindered by unanticipated world events, feasibility was demonstrated. Participants adhered to and were highly satisfied with the combination of pre-cessation varenicline plus ACT. Findings support testing this combined treatment approach in a fully powered trial of persons with BD who smoke.

The association between depression and efavirenz-based antiretroviral treatment in people living with human immune-deficiency virus: a systematic review

The neuropsychiatric disturbance such as depression in people living with (PLHIV) requires serious attention as this affects their health outcome. Efavirenz (EFV)-based treatment has been associated with neuropsychiatric adverse events, but its mechanism still unknown. The purpose of this systematic review is to dissect recent studies regarding EFV and depression, in the hope to discover reasonings behind this association. PRISMA flow chart was used to search for the related literatures in the last five years (2018-2023). Targeted population was PLHIV on EFV-based ART only and/or compared with non-EFV-based ART. Relevant keywords used to search were HIV, efavirenz and depression. Five eligible articles were selected which included a total of 3272 PLHIV. Overall, three studies agreed that EFV-based ART was related to depression, while the other two studies did not. It was shown that EFV-based ART did cause neuropsychiatric adverse effects in the first few weeks of treatment, but subsided after several months. However, longer-term research is needed to determine its long-term effects. Variation of results in different studies must be influenced by the possible genetic factors, baseline depression, different social and psychological circumstances throughout the treatment and different assessment tools for depression. Depression on EFV-based treatment in PLHIV may manifest in the initial few weeks of treatment, and additional research is still needed to determine its effects throughout longer treatment durations. Early diagnosis of depression in PLHIV is essential to decide the best choice of ARV for better outcome.

Propiverine induced pure visual hallucinations without cognitive impairment: A case report

Rationale: Propiverine is believed to have fewer adverse effects on the central nervous system than other anticholinergic medications since it penetrates the blood–brain barrier less deeply. In daily practice, no evidence links propiverine use to neuropsychiatric adverse effects. To our knowledge, this is the first report of psychotic symptoms being linked to propiverine use. Patient concerns: A urologist prescribed 30 mg/day of propiverine capsules to a 62-year-old male patient who complained of urine incontinence and visited the urology outpatient clinic. The patient returned to the urology outpatient clinic a week later because he was experiencing visual hallucinations. Interventions: In the psychiatry outpatient clinic, the patient was conscious, cooperative, and oriented during the mental state examination. He spoke about daylong visual hallucinations that included visions of numerous animals and geometric forms. His mood was somewhat anxious as a result of these images, which started appearing 3 days after taking the propiverine capsule and persisted for 4 days. His cognitive functions were normal. Physical examination, blood chemistry, endocrinology, and brain exams using cranial tomography and electroencephalogram revealed no abnormalities. We advised stopping the medication since visual hallucinations started soon after taking propiverine capsules. Outcomes: After discontinuation of propiverine capsules, the patient’s visual hallucinations disappeared. Lessons: Health practitioners should be aware that adverse effects like visual hallucinations can happen even with anticholinergic medications like propiverine that have a low level of penetration into the blood–brain barrier.

The Risk of Neuropsychiatric Adverse Events With Use of Leukotriene Receptor Antagonists in Patients With Asthma: Analysis of Korea’s National Health Insurance Sharing Service Database

Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning. To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast. This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting β2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group). There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls. We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period.

Neuropsychiatric adverse effects from CFTR modulators deserve a serious research effort.

This review highlights the problem of neuropsychiatric adverse effects (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI), current suboptimal mitigation approaches, a novel testable mechanistic hypothesis, and potential solutions requiring further research. Studies show that a minority of persons with cystic fibrosis (PwCF) initiating cystic fibrosis transmembrane conductance regulator (CFTR) modulators experience neuropsychiatric AEs including worsening mood, cognition, anxiety, sleep, and suicidality. The GABA-A receptor is a ligand-gated chloride channel, and magnetic resonance spectroscopy neuroimaging studies have shown that reduced GABA expression in rostral anterior cingulate cortex is associated with anxiety and depression. Recent research details the impact of peripheral inflammation and the gut-brain axis on central neuroinflammation. Plasma ETI concentrations and sweat chloride have been evaluated in small studies of neuropsychiatric AEs but not validated to guide dose titration or correlated with pharmacogenomic variants or safety/efficacy. Although ETI is well tolerated by most PwCF, some experience debilitating neuropsychiatric AEs. In some cases, these AEs may be driven by modulation of CFTR and chloride transport within the brain. Understanding biological mechanisms is a critical next step in identifying which PwCF are likely to experience AEs, and in developing evidence-based strategies to mitigate them, while retaining modulator efficacy.

Neuropsychiatric Adverse Events Following Antiretroviral Therapy in People Living with HIV: A Real-World Study of Dynamic Trends and Risk Factors in Hangzhou, China.

Neuropsychiatric adverse events (NPAEs) occur frequently in people living with human immunodeficiency virus (PLWH) receiving antiretroviral therapy (ART). This study aimed to assess the dynamic trends and risk factors of NPAEs among PLWH in Hangzhou taking efavirenz (EFV)- or dolutegravir (DTG)- or elvitegravir (EVG)-based regimens. A total of 287 ART-naive PLWH were included in this study, EFV (400mg)- (n = 122), EFV (600mg)- (n = 37), DTG- (n = 73), EVG-based (n = 47) and other ART regimens (n = 8) as the initial ART regimen were administered for 12 months. All data were collected at five time points within a 12-month follow-up. The Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale were used to evaluate sleep disorders and anxiety and depression symptoms, respectively. The dynamic trends and potential risk factors of NPAEs were investigated using a generalized linear mixed model. Mean age was 29.4 (SD: 7.5) years with 97.2% males. After 12 months of ART, the prevalence of sleep disorders and anxiety decreased significantly, although only a slight improvement was observed for depression. In addition, there was a significant positive correlation between sleep disorders, anxiety, and depression. The risk factors for NPAEs differed slightly depending on the choice of ART regimen, but the seven factors most commonly associated with NPAEs were age, sex, marital status, education level, smoking status, body mass index, and WHO clinical stage. Treatment-induced changes in CD4-positive T-cell count and virological suppression did not depend on the particular choice of ART regimen. The prevalence of sleep disorders and anxiety changed significantly over time on ART and the risks of these disorders were associated with seven common clinical anddemographic factors.