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Purpose: The evidence of the neuropsychiatric effects associated with fluoroquinolones is mainly supported by case reports. Population‐based evidence remains largely limited. We aimed to investigate the association between the use of fluoroquinolones and hospitalization or Accident & Emergency department visits for acute neuropsychiatric events using a self‐controlled case series (SCCS) and active comparator to reduce confounding. Methods: We conducted a SCCS with a recently described active comparator design using all public outpatient clinics, hospitalization, and Accident and Emergency department records from the Clinical Data Analysis and Reporting System, Hong Kong from 2001 to 2013. Among 166 325 people with an oral fluoroquinolone prescription, 4287 people who had an incident neuropsychiatric event were included. We then estimated the incidence rate ratio (IRR) of acute neuropsychiatric events during periods before and after fluoroquinolone prescription, versus baseline. We repeated the analysis for amoxicillin/clavulanic acid users as an active comparator. We then estimated the comparator‐adjusted estimates by dividing the IRR for fluoroquinolone by the IRR for amoxicillin/clavulanic acid. The primary outcome was neuropsychiatric events. Secondary outcomes were psychotic events and cognitive impairment. Results: An increased risk of neuropsychiatric events was observed in the current use of fluoroquinolone [IRR: 2.11 (95% confidence interval (CI): 1.58–2.83)] and 1–7 days after the end of fluoroquinolone prescription [IRR: 1.90 (95% CI: 1.30–2.75)] versus baseline. No increased risk was observed in other risk periods versus baseline. Similar patterns were observed in the current use of amoxicillin/clavulanic acid [IRR: 1.92 (95% CI: 1.19–3.11)] and 1–7 days after the end of fluoroquinolone prescription [IRR: 1.81 (95% CI: 1.11–2.97)] versus baseline. Similar results were found for secondary outcomes. Using the active comparator design, comparator‐adjusted estimates were 1.10 (95% CI: 0.63–1.93) in current use of fluoroquinolones and 1.05 (95% CI: 0.57–1.95) in 1–7 days postexposure to fluoroquinolones versus baseline. Conclusions: Although our study showed a higher incidence of neuropsychiatric events in the current use of fluoroquinolones and 7 days after the end of fluoroquinolones prescriptions compared with baseline, a similar temporal pattern was also found for amoxicillin/clavulanic acid users. Using amoxicillin/clavulanic acid as the active comparator, we found no difference in the risk of neuropsychiatric events associated with fluoroquinolone compared with baseline. Therefore, the risk of neuropsychiatric events may not need to influence the decision to prescribe either fluoroquinolones or amoxicillin/clavulanic acid based on the evidence in this study. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract Background In March 2020, the US Food and Drug Administration decided that the dangers related to neuropsychiatric events (NPEs) of montelukast, one of the leukotriene modifying agents (LTMAs), should be communicated through ‘boxed warning’. In case of NPEs, the prevalence has been the highest in elderly people. Because the characteristics of the elderly such as old age itself can act as risk factors. Therefore, an investigation on safety of LTMAs related to NPEs in elderly using LTMAs is needed. Method A nested case-control study using an elderly sample cohort from the Korean National Health Insurance Service database was used. The asthma cohort included asthma patients newly diagnosed between 2003 and 2013. Within the asthma cohort, the case group was defined as patients who were diagnosed with NPEs. Among patients who had never been diagnosed with NPEs, the control group was selected by matching 1:1 by propensity score. Patients who were prescribed LTMAs for 1 year prior to index date were defined as the exposure group. The logistic regression model was used to measure the effect of LTMAs on NPEs. Results We identified 141,165 patients with newly diagnosed asthma, and selected 31,992 patients per each case and control group. Exposure to LTMAs significantly increased the risk of overall NPEs about in comparison with the absence of exposure (crude odds ratio [OR] 1.58, 95% CI 1.50–1.68). After adjusting for confounding factors, the overall NPEs risk increased (adjusted OR, 1.67, 95% CI 1.58–1.78). Conclusion This study suggests that elderly asthma patients prescribed LTMAs had a higher risk of NPEs than patients who were not treated with LTMAs. Therefore, clinicians should be aware of the potential risks of LTMAs.

Abstract Background Total four influenza pandemics have happened since twentieth century, and currently influenza is in the seasonal epidemic around the world, with a sharp increase in its incidence each year. As an effective treatment of influenza infection, the use of oseltamivir is climbing globally. However, there have been reports of neuropsychiatric events associated with the drug, mainly in young patients and males. To our knowledge, this is the first reported case of oseltamivir-associated neuropsychiatric events occurring in an patient over 50-year-old. Case presentation Here we present the case of a 57-year-old Chinese female with H3N2 influenza infection who developed abnormal psychiatric symptoms after administration of high doses of oseltamivir. The patient recovered completely within the cessation of oseltamivir. Conclusions We hope that our case report will lead clinicians to be mindful about oseltamivir’s potential neuropsychiatric side effects, and to pay special attention to each patient’s mental state, both in children and adults.

Background Reports of serious neuropsychiatric events (NPEs), specifically suicide/suicide attempts, following the use of oseltamivir have led to public concerns. Our aim in this study was to determine whether an association exists between oseltamivir use and NPEs. Method This study was a population-based, retrospective, cohort study on a random sample of 50% of individuals in the Korean National Health Insurance Service (KNIS) database aged ≥8 years who were diagnosed with influenza between 2009 and 2017. The primary exposure was oseltamivir prescription at the time of influenza diagnosis, whereas the primary outcome was a diagnosis of an NPE within 30 days after the influenza diagnosis. Information on oseltamivir prescription, diagnoses of NPEs, demographic characteristics, comorbidities, drugs prescribed within the year before influenza diagnosis, and healthcare utilization were extracted from the KNIS database. Results Of 3 352 015 individuals included in the analysis, 1 266 780 (37.8%) were prescribed oseltamivir. The incidence of NPEs was 0.86% and 1.16% in patients who were and were not prescribed oseltamivir, respectively (hazard ratio [HR], 0.74; 95% confidence interval [CI],.73 to.75; P <.001). Oseltamivir use was not associated with a difference in the overall risk of NPEs in the adjusted model (HR, 0.98; 95% CI,.96 to 1.01; P =.16), but the incidence of moderate-to-severe NPEs was significantly lower in those prescribed oseltamivir (HR, 0.92; 95% CI,.88–.96; P <.001). Conclusion Treating influenza with oseltamivir does not increase the risk of NPEs. Thus, public concern regarding its use is unwarranted. [ABSTRACT FROM AUTHOR]

Interferon-based therapies were until recently the standard of care in chronic hepatitis C (CHC), despite their side eff ects. We aimed to review the available data on the depression and suicide in CHC patients receiving or not antiviral therapy based on interferon treatment. A PubMed search was performed, identifying relevant papers published between 1991 and January 2015 concerning major depressive disorders and suicidal risk in patients under interferon. A total of 21 relevant papers were retrieved. Prospective studies reported depression as the most common side eff ect of interferon, with an incidence peak between weeks 8 and 12 of therapy. Suicide risk was analyzed in 7 of the reviewed articles, and case reports of attempted suicide were discussed. Moreover, studies have shown that pretreatment with serotonin reuptake inhibitors is a good strategy for the prevention of interferon-induced depression. [ABSTRACT FROM AUTHOR]

Purpose There is conflicting evidence regarding the association between montelukast and neuropsychiatric events (NE). We sought to examine this association among children with asthma. Methods Using a 10% sample of the LifeLink Health Plan Claims data, subjects less than 18 years of age with a primary diagnosis of asthma between 1 January 1998 and 31 December 2009 were identified. A range of case definitions for NE was formulated based on diagnoses of psychiatric disorders and use of psychotropic medications. Using a matched nested case-control design, three controls were matched to each case on age, gender and geographic region, and assigned a matching index date. Exposure to montelukast was measured as any exposure during the year, recency of exposure, cumulative duration of exposure, and cumulative dose. Conditional logistic regression was used to estimate unadjusted and adjusted odds ratio (OR) controlling for potential confounders. Results Using the broadest case definition, 1920 cases were identified. Subjects exposed to montelukast during the prior year had an unadjusted OR of 1.09 (95%CI [0.96, 1.22]) and adjusted OR of 1.01 (95%CI [0.88, 1.14]) for experiencing NE measured using the broadest definition. A clear dose-response relationship was not observed. Exposure to a moderate chronic cumulative dose of montelukast (481 mg-1050 mg) had a higher odds of being diagnosed with neuropsychiatric disturbances (OR = 1.27; 95%CI [1.03, 1.57]) while exposure to high cumulative doses (>1050 mg) had a lower odds (OR = 0.64; 95%CI [0.50, 0.82]). Conclusions These data did not detect a consistent significant positive association between montelukast and NE in children with asthma. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies. Materials and methods: We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ⩾2. Results: Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review) were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49-1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94-1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2. Conclusion: Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were not detected for mefloquine. Further studies are needed to substantiate this. [ABSTRACT FROM AUTHOR]

Introduction. It has been suggested that neuropsychiatric events during use of mefloquine are more common in females than in males and are partly explained by the psychological stress of travelling. Therefore, we investigated neuropsychiatric events in females and males on mefloquine in the 3-week prophylactic period that precedes travelling. Furthermore, we investigated whether first-time users had a higher risk of neuropsychiatric adverse events than subjects with a history of mefloquine use. Methods. We enrolled all patients who visited a Travel Clinic for mefloquine prophylaxis during the period 1 May 1999 to 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after the start of mefloquine but before travelling. We asked patients to register any adverse event in a diary and measured the intra-individual change in scores on the Dutch Shortened Profile Of Mood States (POMS) at baseline and at the end of follow-up. Results. The final cohort consisted of 179 subjects with a mean age of 3 years. Females reported adverse events more frequently than males (P=0.005). Overall, we observed a small but significant increase in the score on the domain fatigue [0.74 points, 95% confidence interval (CI) 0.18, 1.30]. The effect was exclusively present in females and not in males. First-time users of mefloquine increased 2.81 points (95% CI 0.70, 4.92) on the total score of the POMS, and among those, women showed the largest increase of 4.58 points (95% CI 0.74, 8.43). Conclusion. The use of mefloquine was associated with neuropsychiatric adverse effects. Females encountered neuropsychiatric effects more frequently than males, which could be confirmed by validated psychological tests. Neuropsychiatric effects were more common in first-time users than in individuals who had used mefloquine before. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between montelukast prescription and neuropsychiatric events in children with asthma.Study Design: A matched, nested case-control design was used to identify cases and controls from a cohort of children aged 5-18 years with physician-diagnosed asthma from 2004 to 2015, in Ontario, Canada, prescribed an asthma maintenance medication. Cases were children with a hospitalization or emergency department visit for a neuropsychiatric event. Cases were matched to up to 4 controls on birth year, year of asthma diagnosis, and sex. The exposures were dispensed prescriptions for montelukast (yes/no) and number of dispensed montelukast prescriptions in the year before the index date. Conditional logistic regression was used to measure the unadjusted OR and aOR and 95% CIs for montelukast prescription and neuropsychiatric events. Covariates in the adjusted model included sociodemographic factors and measures of asthma severity.Results: In total, 898 cases with a neuropsychiatric event and 3497 matched controls were included. Children who experienced a new-onset neuropsychiatric event had nearly 2 times the odds of having been prescribed montelukast, compared with controls (OR 1.91, 95% CI 1.15-3.18; P = .01). Most cases presented for anxiety (48.6%) and/or sleep disturbance (26.1%).Conclusions: Children with asthma who experienced a new-onset neuropsychiatric event had nearly twice the odds of having been prescribed montelukast in the year before their event. Clinicians should be aware of the association between montelukast and neuropsychiatric events in children with asthma, to inform prescribing practices and clinical follow-up. [ABSTRACT FROM AUTHOR]

BACKGROUND Studies of neuropsychiatric events in patients with systemic lupus erythematosus (SLE) have shown varied occurrences of manifestations, and their attribution to SLE is inconsistent. OBJECTIVE To investigate the prevalence, characteristics, attribution and clinical significance of neuropsychiatric events in patients with SLE. DESIGN AND INTERVENTION This was an international, multicenter, inception cohort study of patients with SLE, conducted by the members of the Systemic Lupus International Collaborating Clinics (SLICC). Patients included in this study met the American College of Rheumatology (ACR) criteria for SLE. Participants were enrolled in the study up to 15 months after SLE diagnosis. Demographic data on age, sex, ethnicity and education were collected, as well as disease-related data, including history of medication use and scores on the SLE Disease Activity Index (SLEDAI) and the SLICC/ACR Damage Index (SDI) (for patients with disease duration >6 months). Health-related quality of life was also measured using the Short Form 36 (SF-36) Health Survey. A 21-month enrolment window was established for recording neuro- psychiatric events, allowing for events that occurred 6 months prior to the date of diagnosis of SLE and up to 15 months following diagnosis. Neuropsychiatric events were identified using the ACR nomenclature and case definitions for 19 neuropsychiatric syndromes, including a total of 31 neuropsychiatric manifestations. Screening for neuropsychiatric manifestations was performed during clinical evaluation; eight cognitive domains were assessed, including simple attention, complex attention, memory, visual-spatial processing, language, reasoning and problem solving, psychomotor speed and executive functions. Minor neuropsychiatric events, such as headaches, anxiety, and mild depression, events occurring outside the enrolment window, and events that were associated with at least 1 non-SLE factor were classified as not attributable to SLE. Data were analyzed using logistic regression analysis, and a sensitivity analysis was performed to measure the effect of the rules relating to attribution of neuropsychiatric events to SLE. OUTCOME MEASURES The outcome measure of this study was the attribution of a neuropsychiatric event to SLE. RESULTS Data from a total of 572 patients were included in this study. Patients were predominantly female (88%) and the mean ±SD for age and disease duration was 35±14 years and 5.2 ±4.2 months, respectively. A total of 242 neuropsychiatric events were recorded. Two different models were used to determine association with SLE; the occurrence of neuropsychiatric events in patients with SLE was 6.1-11.7% and the proportion of neuropsychiatric events attributed to SLE was 19- 38%. SF-36 scores were significantly lower in all patients who reported neuropsychiatric events (P<0.05), and SDI scores were significantly increased in these patients compared with those who did not report neuropsychiatric events (0.65±1.10 vs 0.29±0.66, P=0.004). [ABSTRACT FROM AUTHOR]