Neuropsychiatric Reactions Research Articles

Quantification of Efavirenz Hydroxymetabolites in Human Plasma Using LC-HRMS/MS.

Efavirenz (EFV) is a drug used to treat HIV. Low plasma concentrations of EFV result in suboptimal viral suppression, whereas high concentrations can cause adverse neuropsychiatric side reactions. Some studies have identified a correlation between the plasma concentrations of EFV metabolites and neurotoxicity. To our knowledge, no studies have investigated the metabolism of EFV in young children and its effect on treatment outcomes. Therefore, the aim of this study was to develop and validate a method for quantifying EFV and its metabolites in human plasma derived from children. Sample preparation was performed using protein precipitation of 100 µL plasma. Thereafter, an aliquot of the supernatant was used to quantify EFV, 7-hydroxyefavirenz (7-OH-EFV), 8-hydroxyefavirenz (8-OH-EFV), and a newly discovered metabolite ("EFAdeg") associated with 8-OH-EFV. A second aliquot of the supernatant was hydrolyzed using β-glucuronidase/arylsulfatase and used with the first aliquot to quantify phase II metabolites. The analyses were performed using a Dionex Ultimate 3000RS LC-system coupled with a Q Exactive Orbitrap mass spectrometer. The method has a measuring range of 100-50,000 ng/mL (EFV, 8-OH-EFV), 125-25,000 ng/mL (7-OH-EFV), and 200-10,000 ng/mL ("EFAdeg"). All criteria of the European Medicines Agency guidelines regarding precision, accuracy, and selectivity were met. Of note, carryover must be considered for 8-OH-EFV. Overall, the validated method was successfully applied to plasma samples obtained from children and confirmed the presence of the newly discovered metabolite, "EFAdeg." An LC-HRMS/MS method for the quantification of EFV and its phase I and II metabolites was developed and validated. This method is suitable for analyzing plasma samples from children. Furthermore, studies using this method identified an additional metabolite that may influence the concentration of 8-OH-EFV in patient samples.

Black boxed warnings on montelukast-related neuropsychiatric reactions

Black boxed warnings on montelukast-related neuropsychiatric reactions

Montelukast will carry 'more prominent warnings’ of neuropsychiatric reactions

Montelukast will carry 'more prominent warnings’ of neuropsychiatric reactions

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.

Analysis of the efficacy of subclinical doses of esketamine in combination with propofol in non-intubated general anesthesia procedures - a systematic review and meta-analysis

BackgroundThe number of non-intubated general anesthesia outside the operating room is growing as the increasing demand for comfort treatment. Non-intubated general anesthesia outside the operating room requires rapid onset of anesthesia, smoothness, quick recovery, and few postoperative complications. Traditional anesthetic regimens (propofol alone or propofol and opioids/dezocine/midazolam, etc.) have severe respiratory and circulatory depression and many systemic adverse effects. In this paper, we compare the effectiveness and safety of propofol and subclinical doses of esketamine with other traditional regimens applied to non-intubated general anesthesia through a systematic review and meta-analysis.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Sinomed databases for the period from January 2000 to October 2022. We rigorously screened the literature according to predefined inclusion and exclusion criteria, while risk assessment of the studies was performed using The Cochrane Collaboration’s tool, and statistical analysis of the data was performed using RevMan 5.4 software. The main outcome indicators we evaluated were the various hemodynamic parameters and incidence of various adverse effects between the experimental and control groups after induction of anesthesia.ResultsAfter a rigorous screening process, a total of 14 papers were included in the final meta-analysis. After risk bias assessment, three of the papers were judged as low risk and the others were judged as having moderate to high risk. Forest plots were drawn for a total of 16 indicators. Meta-analysis showed statistically significant differences in HR’ WMD 3.27 (0.66, 5.87), MAP’ WMD 9.68 (6.13, 13.24), SBP’ WMD 5.42 (2.11, 8.73), DBP’ WMD 4.02 (1.15, 6.88), propofol dose’ SMD -1.39 (-2.45, -0.33), hypotension’ RR 0.30 (0.20, 0.45), bradycardia’ RR 0.33 (0.14, 0.77), hypoxemia or apnea’ RR 0.45 (0.23, 0.89), injection pain’ RR 0.28 (0.13, 0.60), intraoperative choking’ RR 0.62 (0.50, 0.77), intraoperative body movements’ RR 0.48 (0.29, 0.81) and overall incidence of adverse reactions’ RR 0.52 (0.39, 0.70).The indicators that were not statistically different were time to wake up’ WMD − 0.55 (-1.29, 0.19), nausea and vomiting 0.84’ RR (0.43, 1.67), headache and dizziness’ RR 1.57 (0.98, 2.50) and neuropsychiatric reaction’ RR 1.05 (0.28, 3.93). The funnel plot showed that the vast majority of studies fell within the funnel interval, but the symmetry was relatively poor.ConclusionIn non-intubated general anesthesia, the combination of subclinical doses of esketamine and propofol did reduce circulatory and respiratory depression, injection pain, and other adverse effects, while the incidence of esketamine’s own side effects such as neuropsychiatric reactions did not increase, and the combination of the two did not cause the occurrence of new and more serious adverse reactions, and the combination of the two was safe and effective.Trial registrationPROSPREO registration number: CRD 42022368966.

Risk factors for health in medical workers of modern dental practice (literature review)

The analysis of the data of foreign and domestic literature devoted to the main risk factors for health is carried out and presented, the diseases of medical workers of modern dental practice that are more common at present are studied and described. A distinctive feature of the work of practicing dentists is the influence on their body of a complex of unfavourable factors of the production environment of occupational and non-occupational genesis (biological, chemical, physical and factors of the labour process). It is also common for them to be affected by the intensity of the labour process, which is expressed by significant psycho-emotional stress. Dentists are often at high risk of infection and transmission of dangerous pathogens: viruses (herpes, human immunodeficiency virus, hepatitis B and C, including new coronavirus infection (COVID-19)), bacteria (staphylococcus, tuberculosis), fungi. They have a high prevalence of injuries to the visual organ and upper extremities, allergic reactions. Among dental personnel in countries using amalgam during work, changes in neuropsychiatric reactions, memory loss, and fatigue are described; changes in biochemical parameters of blood, urine analysis are revealed. Physiological and ergonomic loads of dental service specialists and uncomfortable postures associated with work lead to the development of diseases of the musculoskeletal system and the appearance of pain, and affect their quality of life. Despite the harmlessness of the noise level in modern dentistry, the sounds produced by devices at work affect the mental health of dentists. Dental professionals with long work experience are predisposed to the highest risk of hearing loss. Today, dentists continue to show carpal tunnel syndrome and rarely vibration disease from exposure to local vibration. Medical workers of modern dental practice are shown to be affected by a complex of unfavourable factors of the low-intensity production environment and develop diseases associated with their occupational activities.

Self‐reported neuropsychiatric adverse reactions in people receiving bictegravir combined with emtricitabine/tenofovir alafenamide

AbstractThe integrase‐inhibitor bictegravir combination antiretroviral therapy (ART) Biktarvy became available in Australia in October 2018. Neuropsychiatric adverse drug reactions (ADRs) are associated with bictegravir and may affect persistence and adherence to treatment. The aim of this study was to describe the type and frequency of reported neuropsychiatric reactions in people dispensed Biktarvy. Ethics approval was obtained from Alfred Hospital Ethics Committee (Project No. 541/20). Data were collected from records of people dispensed Biktarvy between October 2018 and May 2020 and who subsequently had a new neuropsychiatric reaction reported to the organisation's ADR Review Committee. Data were sourced from ADR reports, medical and dispensing records, and included demographics, medical history, and concurrent medicines with known psychiatric adverse reactions. Data were analysed descriptively. Biktarvy was dispensed to 1265 patients. Twenty‐two (1.7%, 95% confidence interval [CI] 1.0–2.5%) people reported 50 neuropsychiatric ADRs, including abnormal dreams (n = 13), sleep disorders (n = 5), and headaches (n = 5). The median time from initiation to reaction was 13 (interquartile range [IQR] 4–94) days. Eighteen patients discontinued Biktarvy (1.4%, 95% CI 0.85–2.24). There was no statistically significant difference in discontinuation of Biktarvy between people who did or did not have a pre‐existing psychiatric diagnosis (p = 0.58). Concurrent medicines with known psychiatric adverse reactions were used by 10 people. A low rate of reported neuropsychiatric ADRs lead to discontinuation of Biktarvy, similar to rates in Biktarvy trials. This study adds to the post‐marketing surveillance data of Biktarvy tolerance amongst people living with human immunodeficiency virus (HIV).

Adverse Drug Reactions (ADRs) of Montelukast in Children.

To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders. We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4-9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%). These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans.

The mechanisms underlying montelukast's neuropsychiatric effects - new insights from a combined metabolic and multiomics approach

AimsMontelukast (MTK) is an antagonist of the cysteinyl leukotrienes receptor 1 widely used to manage asthma symptoms among adults and children. However, it has been associated with an increasing number of neuropsychiatric adverse drug reactions (ADRs), particularly among children, including depression, sleep disturbance, and suicidal ideation. The aims of this work were to characterize MTK metabolism in vitro and in vivo and to identify its effects at the metabolome and proteome levels in order to explain its toxicity. Main methodsAn extensive study of montelukast metabolism was carried out using in vitro systems, an embryonic neuron-enriched cell model, and a mouse model. Metabolites were identified by high-resolution mass spectrometry, and a combined mass spectrometry-based metabolomics and proteomics approach was employed to assess the effect of MTK on mice and isolated chicken neurons. Key findingsEighteen new MTK metabolites were identified. MTK's ability to react with glutathione was confirmed. The multi-omics approach employed confirmed that montelukast interferes with the glutathione detoxification system in the brain. Moreover, montelukast is also able to dysregulate various neurotransmitter and neurosteroid pathways, particularly those involved in regulation of the hypothalamic–pituitary–adrenal axis, also interfering with mitochondrial function in neuronal cells. SignificanceResults clearly indicate that montelukast therapeutic effects are accompanied by a strong modulation of specific processes in the central nervous system that may explain the observed neuropsychiatric reactions. Moreover, the results also suggest that adverse drug reactions are more likely to occur in children, due to the early maturation stage of their brains.

Reações adversas do montelucaste no tratamento da asma pediátrica: uma revisão integrativa da literatura

We analyzed the adverse reactions of montelukast when prescribed for the treatment of pediatric asthma. This is an integrative literature review using the databases: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS and Business Source Complete (EBSCO), using the descriptors: "asthma", "pediatric", "montelukast" and "adverse effects", connected by the Boolean “ AND''. Articles in full were included, published in the last 5 years, written in Portuguese, English or Spanish, researched in humans and related to our objective. Those that met our exclusion criteria were excluded. Fifty-three articles were identified, of which 11 comprised the final sample of this review. Exposure to montelukast was associated with a 2-fold greater chance of neuropsychiatric reactions in one of the articles analyzed, but the studies have not yet provided a common pathophysiological explanation. Neuropsychiatric reactions were the most prevalent, representing more than 90% of the sample.

Does COVID-19 related symptomatology indicate a transdiagnostic neuropsychiatric disorder? - Multidisciplinary implications.

The clinical presentation that emerges from the extensive coronavirus disease 2019 (COVID-19) mental health literature suggests high correlations among many conventional psychiatric diagnoses. Arguments against the use of multiple comorbidities for a single patient have been published long before the pandemic. Concurrently, diagnostic recommendations for use of transdiagnostic considerations for improved treatment have been also published in recent years. In this review, we pose the question of whether a transdiagnostic mental health disease, including psychiatric and neuropsychiatric symptomology, has emerged since the onset of the pandemic. There are many attempts to identify a syndrome related to the pandemic, but none of the validated scales is able to capture the entire psychiatric and neuropsychiatric clinical presentation in infected and non-infected individuals. These scales also only marginally touch the issue of etiology and prevalence. We suggest a working hypothesis termed Complex Stress Reaction Syndrome (CSRS) representing a global psychiatric reaction to the pandemic situation in the general population (Type A) and a neuropsychiatric reaction in infected individuals (Type B) which relates to neurocognitive and psychiatric features which are part (excluding systemic and metabolic dysfunctions) of the syndrome termed in the literature as long COVID. We base our propositions on multidisciplinary scientific data regarding mental health during the global pandemic situation and the effects of viral infection reviewed from Google Scholar and PubMed between February 1, 2022 and March 10, 2022. Search in-clusion criteria were “mental health”, “COVID-19” and “Long COVID”, English language and human studies only. We suggest that this more comprehensive way of understanding COVID-19 complex mental health reactions may promote better prevention and treatment and serve to guide implementation of recommended administrative regulations that were recently published by the World Psychiatric Association. This review may serve as a call for an international investigation of our working hypothesis.

Neuropsychiatric reactions with the use of montelukast.

### What you need to know A 13 year old boy was started on 5 mg montelukast daily in addition to low dose inhaled corticosteroids to treat his asthma. Within a few days, his mother noted that he was constantly arguing and wanted to hit and kick other people. He had not shown this behaviour earlier. At the time of prescribing, their doctor had asked for any history of psychiatric illnesses in their family, which they had none. The doctor had advised her to observe the child and report any changes in behaviour after starting the drug. Montelukast, used in patients with asthma or allergic rhinitis, is associated with a risk of neuropsychiatric adverse reactions (see box 1). These are uncommon and usually mild but can be worrisome and affect quality of life for patients and their families. Rarely, serious adverse reactions such as depression and suicide have been reported, mostly with prolonged use.8 Neuropsychiatric symptoms may be attributed to normal behavioural changes in children or to other conditions. Failure to recognise these adverse drug reactions early can result in serious harm to patients and their families. Box 1 ### Regulatory approval and safety warningsRETURN TO TEXT

Neuropsychiatric side reactions of leukotriene receptor antagonist, antihistamine, and inhaled corticosteroid: A real-world analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS)

BackgroundThere are limited real-world studies on the differences in leukotriene receptor antagonists (LTRA), H1-antihistamines (H1-AH), and inhaled corticosteroids (ICS) associated neuropsychiatric events. In this study, we aimed to analyze the characteristics of drug associated neuropsychiatric events, and compare the differences among different drug categories. MethodsDisproportionality analysis and Bayesian analysis were used in data mining to identify suspected neuropsychiatric events associated with LTRA, H1-AH, and ICS based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2004 to September 2020. Demographic information, time interval to onset, and death rates of LTRA, H1-AH, and ICS-associated neuropsychiatric events were also analyzed. ResultsA total of 9475 neuropsychiatric events were identified. The number of neuropsychiatric events related to LTRA, H1-AH, and ICS were 5201 (54.89%), 3226 (34.05%), and 1048 (11.06%), respectively. LTRA related neuropsychiatric events were more common in patients aged 4–6 years (18.66%). H1-AH and ICS related neuropsychiatric events were more common in patients aged 18–44 years (29.92%) and older than 65 years (30.60%), respectively. Montelukast was highly associated with neuropsychiatric events, with a high reporting odds ratio (ROR). Most neuropsychiatric symptoms occurred within the first 10 days after drug initiation (78.63% for LTRA, 91.39% for H1-AH, and 84.07% for ICS). The death rate due to neuropsychiatric events of first generation H1-AH was significantly higher than that of LTRA and ICS (p < 0.001). ConclusionsLTRA associated neuropsychiatric events reported in FAERS were most frequent in 4 to 6-year-old children. Most reported cases occurred within the first 10 days after drug initiation. The second generation H1-AH was relatively safe for neuropsychiatric events compared with the first generation. The fatality rate due to first generation H1-AH associated neuropsychiatric events was higher than that of LTRA and ICS. More attention should be paid to specific patients treated with LTRA and H1-AH.

13711 Isotretinoin use in acne is associated with a higher odds of the adverse effect of insomnia: Results from the US FDA Adverse Events Reporting System

Background: Isotretinoin has been associated with a higher risk for potentially serious neuropsychiatric adverse events (AE), eg, suicide. Insomnia can be the initial presenting symptom of many neuropsychiatric reactions.

Особливості використання нейробіозворотного тренінгу для корекції пізнавальних функції у похилому віці

. Використання нейробіозворотного тренінгу(НБТ) перспективний метод відновлення пізнавальних функції. На сьогоднішній день остаточно нез'ясовано нейронні механізми, що лежать в основі успішного навчання нейробіозворотному зв'язку.&#x0D; При численних дослідах застосування нейробіозворотний тренінгу (НБТ) було виявлено декілька активних ділянок мозку. Які можна об’єднати в три основні групи: контроль, обробка винагороди, навчання, що являють собою об’єднану мережу. У випадку візуального зворотного зв'язку увага до сигналу регулюється бічною потиличною корою (БПК). Дорсолатеральна префронтальна кора (ДЛПФК) і задня тім'яна кора (ЗТК) беруть участь у здійсненні виконавчих завдань, та з’єднані з таламусом, котрий регулює кортикальне збудження. Передня сингулярна кора (ПСК) та передня інсулярна кора (ПІК) беруть участь у свідомому сприйнятті зворотного зв'язку та винагороди. У вентральному стріатумі (ВС) відбувається несвідома обробка винагороди . Дорсальний стріатум (ДС) пов'язаний з навчанням НБЗ. В процесі здійснення нейрофідбеку, навчання триватиме до отримання навички, котре передбачає початкову фазу швидких змін у продуктивності та пізню фазу більш поступового поліпшення та зміцнення навиків. Було показано, що функціональні та структурні зміни у дорсомедіальному стріатумі асоціюються з ранньою фазою, тоді як такі зміни в дорсолатеральному стріатумі, пов'язані з пізньою фазою.&#x0D; Кожна з груп пов’язана із специфічними хімічними нейромедуляторами: холінергічна система, що виникає у базальному передньому мозку, відіграє важливу роль у орієнтації, концентрації уваги, пам’яті і когнітивних функцій; норадреналінова система, що виникає в голубій плямі, бере участь у підтриманні рівня активності нервово-психічних реакцій, формуванні когнітивних та адаптивних процесів.; і передня сингулярна кора та бічна префронтальна кора є цільовими областями мезокортикальної системи дофаміну, що бере участь у виробленні винагороди та підкріплення. Крім того проявляється в основному дисфункцією в початковій фазі при застосуванні НБТ. Відповідно ймовірніше пояснення функціонування НБТ побудоване на мозковій системі контролю та системі винагороди.&#x0D; Що до літніх осіб, їхня нейропластичність зменшується з віком, відповідно це призводить до погіршення активності передніх відділів кори головного мозку та послаблення виконання контрольних та виконавчих функцій, які контролюються дофаміновою системою. З цього випливає необхідність більшої кількості сеансів НФ та більш інтенсивної винагороди для отримання позитивного ефекту від навчання, порівняно з дослідженнями, заснованими на молодих людях.

SFDA warns of neuropsychiatric reactions with montelukast

SFDA warns of neuropsychiatric reactions with montelukast

Hypothermic Action of Oseltamivir Not Dependent on Its Anti-influenza Virus Action

Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that oseltamivir causes dose-dependent hypothermia in normal mice, and have been studying the pharmacological mechanisms responsible for 12 years. Oseltamivir blocks nicotinic cholinergic transmission at sympathetic ganglia and reduces sympathetic modulation of brown adipose tissue (BAT), a heat generator. Oseltamivir was found to target the ion channels of nicotinic acetylcholine receptors, as demonstrated by patch clamp experiments with cells expressing the human α3β4 nicotinic receptor. Metabolized oseltamivir carboxylate, which inhibits the influenza virus neuraminidase, did not elicit hypothermia and ion channel suppression. Body temperature was decreased by intracerebroventricular administration of oseltamivir. Because this hypothermic effect was inhibited by dopamine D2 receptor blockade, it was suggested that oseltamivir centrally stimulates the D2 receptor. In Japan, the package inserts for oseltamivir and amantadine indicate very similar adverse neuropsychiatric reactions for the two drugs (abnormal behavior, consciousness disturbance, convulsion, delirium, delusion, hallucination). A literature search revealed that in some previous studies, oseltamivir and amantadine were shown to block the ion channel systems and activate the dopaminergic nervous system via several mechanisms. Therefore the similarity of the adverse reactions elicited by oseltamivir and amantadine was considered attributable to their similar pharmacological effects.

23. An adverse neuropsychiatric reaction following treatment with hydroxychloroquine: a case report

23. An adverse neuropsychiatric reaction following treatment with hydroxychloroquine: a case report

Perspectives for the Electroencephalogram in Psychiatry

Perspectives for the Electroencephalogram in Psychiatry Abstract. The electroencephalogram (EEG) is a non-invasive and cost-effective method to monitor spontaneous neuronal activity over time. Pathologies in EEG recordings indicate with high sensitivity but low specificity abnormal functional brain states. The main psychiatric indications for EEG recordings include atypical clinical symptoms of a neuropsychiatric syndrome or atypical reactions to medication as well as a baseline diagnostic before starting treatment with specific drugs or stimulation modalities. In recent research the EEG continues to be a valuable tool not only in diagnostics but also for the prediction of treatment success. The following paper focuses on basic electrophysiological understanding of EEG recordings, the diagnostic value of EEG recordings in different clinical entities, and new research attempts in diagnostic and treatment prediction.

Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)

The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.