Neuropsychiatric Adverse Drug Reactions Research Articles

Adverse drug reactions of montelukast in children and adults.

Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5–7.4). In the VigiBase®, aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5–32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61–3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase®. These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice.

Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children.We conducted a retrospective cohort study in children aged 1-17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event.Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3-8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10-26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast versus ICS was 12 (2-90).In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk ofneuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated withICS.

May direct-acting antiviral regimens for chronic hepatitis C virus infections have neuropsychiatric adverse drug reactions? A pilot study conducted in patients receiving sofosbuvir-based regimens in the real-life setting

Until 2011, the standard-of-care therapy for chronic hepatitis C virus (HCV) infections relied on pegylated interferon, whose psychiatric adverse drug reactions are well known to treating physicians. From 2014, direct-acting antivirals (DAAs) with fewer adverse drug reactions and not contraindicated in patients affected by psychiatric disorders have been used. The aim of the present study is to assess the development of psychiatric effects related to DAA regimens based on sofosbuvir in the real-life setting. A pilot retrospective study in the real-life setting, based on administration of a battery of anonymous assessment scales, including the Specific Level Of Functioning assessment and health physical inventory (SLOF) and the Structured Clinical Interview for DSM-IV Axis II disorders (SCID II), was conducted in a sample of 27 adult patients (13 males and 14 females) with chronic HCV infection and F3/F4 fibrosis who had completed a 3- or 6-month sofosbuvir-based DAA regimen. This schedule ended on January 1, 2016. Statistical analysis was performed using SPSS PASW-statistic 18.0. At the end of our study, 13 of the 27 enrolled patients (48.14%) reported having psychiatric symptoms during and/or after therapy, while the remaining 14 patients denied experiencing any symptoms. The most common symptoms were anxiety (40.7 and 29.6% psychic and somatic type, respectively), stress (46.2%), depressed mood (18.5%), hypochondria (18.5%), initial, middle and delayed insomnia (14.8% for each type), fear (14.8%), modification of the intellectual sphere (14.8%), and irritability (14.8%); no suicide attempt or depersonalization/de-realization disorder were reported. No patients withdrew from therapy due to psychiatric adverse drug reactions. This pilot study seems to indicate that the occurrence of the psychiatric effects seems to be more frequent than previously reported in the registration trials or the summary of product characteristics, which is likely due to different characteristics between the patients enrolled in the registration trials and the patients in daily clinical practice. Since the therapy can currently be offered to many patients with chronic HCV infection who in the past were excluded from treatment because of psychiatric or mental disorders, only a prospective trial in the real-life setting may assess the real impact of therapy with DAAs on the patients’ psychiatric sphere.

Incidence and risk factors for neuropsychiatric events among Ghanaian HIV patients on long-term non-nucleoside reverse transcriptase inhibitor-based therapy.

BackgroundNon-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is associated with neuropsychiatric toxicity. Little is known about the risk of short- and long-term neuropsychiatric toxicity in sub-Saharan Africa, where NNRTIs are widely used in first-line combination ART. This observational study assessed the risk of neuropsychiatric toxicity in Ghanaian patients starting first-line ART between 2004 and 2010 at a single centre.MethodsIn this retrospective observational study, frequencies of documented neuropsychiatric toxicity events were assessed and time to events calculated using a Kaplan–Meier analysis. Associations of neuropsychiatric toxicity with specific NNRTIs and other explanatory variables were examined using Cox proportional hazards modelling.ResultsOf 3999 patients initiating NNRTI-based ART, who were followed for a median of 30 (0.25–90) months (11,237 person years), 218 (5.5%) reported symptoms of neuropsychiatric toxicity at a rate of 21.4 events per 1000 person-years (95% CI, 18.8–24.2/1000 py). Events were more common with efavirenz than nevirapine (7.6% versus 2.4%), were usually reported within the first 2 months of ART initiation and persisted up to 84 months in a few patients. The most commonly reported neuropsychiatric adverse drug reactions were insomnia (50%), headaches (8%), dizziness (7%) and abnormal dreams (6%). The factors independently associated with neuropsychiatric toxicity were BMI < 16 kg/m2 (aHR of 1.44 [95% CI, 1.02–2.03]) and use of efavirenz (aHR 3.29 [95% CI, 2.32–4.69]). Substitution of NNRTI on account of toxicity was reported in up to 17% of patients experiencing neuropsychiatric events.ConclusionsNNRTI-related neuropsychiatric toxicity, mainly due to efavirenz, was infrequently documented in this Ghanaian cohort under routine clinical care settings. Regimens with more favourable tolerability will be needed as first-line agents in sub-Saharan Africa in the coming years.

Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz.

Adverse drug reactions associated with efavirenz (EFV) therapy are poorly described beyond the first year of treatment. We aimed to describe the incidence and predictors of EFV-related adverse drug reactions (ADRs) in a cohort of adult Nigerian HIV-infected patients on antiretroviral therapy (ART). This retrospective cohort study utilized clinical data of HIV-1 infected adults (aged ≥15 years), commenced on efavirenz containing-regimen between January 2004 and December 2011. The time-dependent occurrence of clinical adverse events as defined by the World Health Organization was analyzed by Cox regression analysis. A total of 2920 patients with baseline median (IQR) age of 39 (33-46) years, largely made up of men (78%) were included in the study. During 8834 person-years of follow up, 358 adverse drug events were reported; the incidence rate was 40.3 ADRs per 1000 person-years of treatment. Lipodystrophy and neuropsychiatric disorders were the most common ADRs with incidences of 63 and 30 per 1000 patients respectively. About one-third of the neuropsychiatric adverse events were within 12 months of commencement of ART. The risk of neuropsychiatric ADRs was independently predicted for women [adjusted hazard ratio (aHR) 9.05; 95% CI: 5.18-15.82], those aged <40 years (aHR 2.59; 95% CI: 1.50-4.45), advanced HIV disease (WHO stage 3 or 4) [aHR 2.26; 95% CI: 1.37-3.72], and zidovudine [aHR 2.21; 95% CI: 1.27-3.83] or stavudine [aHR 4.22; 95% CI: 1.99-8.92] containing regimen compared to tenofovir. Neuropsychiatric adverse drug events associated with efavirenz-based ART had both early and late onset in our clinical cohort of patients on chronic EFV therapy. Continuous neuropsychiatric assessment for improved detection and management of neuropsychiatric ADRs is recommended in resource-limited settings where the use of efavirenz-based regimens has been scaled up.

Online Reporting of Adverse Drug Reactions: A Study from a French Regional Pharmacovigilance Center

BackgroundIn France, online reporting via a website is a new method for notifying adverse drug reactions (ADRs). The French Midi-Pyrénées Regional Pharmacovigilance Center (RPVC) set up in July, 2010a Web-based ADR reporting tool in order to improve ADR reporting rate. ObjectivesTo assess feasibility, use and performances of this new ADR reporting system. To evaluate the main characteristics of these online reports. MethodsIn a retrospective study, we evaluated characteristics (numbers, ADR reporting and file processing times, type of reporters, suspected drugs, “seriousness” and nature of ADRs) of online notifications reported to the RPVC between July 7th, 2010 (first online notification) and December 31th, 2011. We performed comparisons to a random sample of “conventional” notifications, i.e. spontaneously reported to the RPVC via traditional tools (post, fax, e-mail or telephone) during the same period. ResultsThe total number of online reports was 312 over the 18-month period. There was a 45% increase in numbers of reports from ambulatory healthcare professionals after the implementation of the new reporting tool. Online reports were transmitted to the French Medicine Agency on average almost one month (26days) earlier than “conventional” ones. This difference was mainly due to a faster ADR notification process via the online form (on average, the reporting period was decreased by 19days with the new tool). In comparison to “conventional” notifications, online reports came more often from ambulatory healthcare professionals, and involved more frequently neuropsychiatric drugs and neuropsychiatric ADRs. None difference was observed for “seriousness” of ADRs. ConclusionsIt is feasible to deploy an online ADR reporting system used by health professionals in current practice. We underline the efficiency of this new online reporting tool for increasing ADRs reporting. Moreover, this is the first published study demonstrating that an online reporting tool can help to save time on the ADR reporting period and file processing, which is essential to generate early safety signals.

Adverse Drug Reactions to Gabapentin and Pregabalin

Gabapentin and pregabalin are widely used as antineuropathic pain drugs. Their use is also associated with the development of adverse drug reactions (ADRs), mainly neuropsychiatric. The aim of this work was to study 'serious' and/or 'unexpected' adverse reactions associated with pregabalin and gabapentin. We studied ADRs reported to the French Pharmacovigilance System occurring between 1995 and 2009. For each ADR associated with gabapentin or pregabalin, we noted year, patient age and sex, type of adverse reaction, as well as the imputability score. Reporting rate of serious ADRs for gabapentin and pregabalin was estimated with regard to data of use (obtained from the French National Health Insurance Fund) using the defined daily dose. A global and descriptive analysis of the adverse reactions for each drug is presented. Secondly, details of deaths and ADRs with an imputability score of at least 'probable' or 'likely' were presented. Overall, 1333 cases were recorded (725 related to gabapentin, 608 related to pregabalin), mainly neuropsychiatric ADRs. Among the 22 deaths recorded, 8 were related to gabapentin in obstetrical situations. Other less well-documented ADRs were identified, such as hepatitis associated with gabapentin and haematological ADRs associated with pregabalin. This study confirmed the prevalence of neuropsychiatric ADRs associated with gabapentin or pregabalin. A high rate of death occurred with gabapentin in an obstetrical context. New adverse reactions have been noted, such as haematological or hepatic adverse reactions associated with pregabalin and gabapentin, respectively.

A manic episode in a 64-year-old man: an adverse effect of varenicline

Varenicline is a novel treatment for smoking cessation. However, it has not been well studied in patients with medical and psychiatric comorbidity. We report a case of an acute manic episode in a 64-year-old man with a history of bipolar disorder post stroke, who was started on varenicline. This case demonstrates the importance of monitoring neuropsychiatric adverse drug reactions after the start of varenicline therapy in patients with a current or past history of mental illness.

P.1.c.017 Neuropsychiatric adverse drug reactions (ADRs) and neuropsychiatric drugs-induced ADRs in a tertiary care hospital

P.1.c.017 Neuropsychiatric adverse drug reactions (ADRs) and neuropsychiatric drugs-induced ADRs in a tertiary care hospital

Neuropsychiatric Adverse Drug Reactions in General Practice

Neuropsychiatric Adverse Drug Reactions in General Practice

Neuropsychiatric reactions to drugs: an analysis of spontaneous reports from general practitioners in Italy

Limited information is available on drug-induced neuropsychiatric disorders in general practice. The spontaneous reports of both neurological and psychiatric adverse drug reactions (ADRs) collected during a 2-year period in PharmaSearch database, an Italian database recording reports of ADRs from general practitioners (GPs), were examined. Between January 2002 and December 2003, 171 general practitioners sent to PharmaSearch a total of 1131 reports corresponding to 1892 ADRs. Of overall reports, 310 (27.4%) involved the central nervous system resulting in 440 neuropsychiatric reactions (specifically, 241 neurological and 199 psychiatric). In our survey, 40 reports were excluded because they were incomplete or contradictory and thus classified as ‘unlikely’ or ‘unclassifiable’. Therefore, the present analysis was carried out on 270 reports with 391 neuropsychiatric reactions (213 neurological and 178 psychiatric, respectively). Vertigo (16.4%), confusion (10.7%) and headache (10.0%) were the reactions more commonly reported. Drugs indicated for the treatment of nervous system disorders (ATC 1 code = N) accounted only for 38.4% of neuropsychiatric reactions, while most of these reactions were related to drugs indicated for other than nervous system diseases. Non-steroidal anti-inflammatory drugs (NSAIDs), fluoroquinolones, antidepressant drugs, opioids, and drugs for peptic ulcer were the categories most frequently suspected for neuropsychiatric reactions. Of 391 neuropsychiatric reactions, 78 (19.9%) were unlabeled and 41 (10.5%) were serious. In conclusion, the present study carried out in general practice underlines the importance of neuropsychiatric ADRs and reminds GPs to pay attention to this kind of toxicity when they prescribe pharmacological agents to their patients.

Neuropsychiatric adverse drug reactions: passive reports to Health and Welfare Canada's adverse drug reaction database (1965-present).

Since 1965, Health and Welfare Canada has operated an adverse drug reaction (ADR) program. The program accepts spontaneous reports of adverse drug reactions, and maintains an ADR database. The purpose of this article is to summarize the Psychiatric ADRs reported to this database since 1965. The nature of the information prohibits its use in the evaluation of epidemiological hypotheses about the etiology of drug-induced mental disorders. However, in an exploratory sense, the contents of the database may contribute to the development of epidemiological hypotheses about the etiology of drug-induced mental disorders. Of particular interest are areas of apparent contradiction between the contents of the database and the clinical literature. The database was searched for reports of ADRs to a group of drugs which have been frequently implicated in causing psychiatric toxicity. All reports characterized as "psychiatric disorders" were down-loaded from the database for the analysis (n = 1822). The reports were further classified into nine categories according to the type of psychiatric symptoms described. There were several reports of hallucinations caused by methyldopa, and also several reports of benzodiazepine-induced hallucinations and encephalopathy. These reactions have not been described in the literature. Also, there were few reports of digoxin-induced organic depression, and an absence of reports of organic mania induced by H-2 blockers, despite descriptions of these sorts of reactions in the clinical literature. Further research is needed to define the neuropsychiatric toxicity associated with medical drugs. Clinicians must continue to consider the potential role of medications in the etiology of psychiatric symptoms.