Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis.
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ABSTRACT:
SUBMITTER: Brueckle MS
PROVIDER: S-EPMC7079360 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis.
Brueckle Maria-Sophie MS Thomas Elizabeth T ET Seide Svenja E SE Pilz Maximilian M Gonzalez-Gonzalez Ana Isabel AI Nguyen Truc Sophia TS Harder Sebastian S Glasziou Paul P PP Gerlach Ferdinand M FM Muth Christiane C
Systematic reviews 20200317 1
<h4>Background</h4>Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-the-counter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy in ...[more]
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Project description:BackgroundHalf the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals.MethodsWe searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups.ResultsTwenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd's ratio for amitriptyline versus placebo (OR = 7.41; [95% CI, 4.54 to 12.12]). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent.DiscussionThe large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (<100 participants) decreased heterogeneity between studies, but may also have reduced our ability to detect rare events. Future studies should focus on older people, as they are more susceptible to anticholinergic ADRs.RegistrationPROSPERO: CRD42020111970.
| S-EPMC10075391 | biostudies-literature
Project description:BackgroundAdverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.Methods and findingsWe searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%-98% of ADRs being either definitely/possibly avoidable.ConclusionsThere is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.
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Project description:Introduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6-68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96513, identifier CRD42018096513.
| S-EPMC8850382 | biostudies-literature
Project description:BackgroundAdverse drug reactions (ADRs) represent a major cause of iatrogenic morbidity and mortality in patient care. While a substantial body of work has been undertaken to characterise ADRs in the hospital setting, the overall burden of ADRs in the primary care remains unclear.ObjectivesTo investigate the prevalence of ADRs in the primary care setting and factors affecting the heterogeneity of the estimates.MethodsStudies were identified through searching of Medline, Embase, CINAHL and IPA databases. We included observational studies that reported information on the prevalence of ADRs in patients receiving primary care. Disease and treatment specific studies were excluded. Quality of the included studies were assessed using Smyth ADRs adapted scale. A random-effects model was used to calculate the pooled estimate. Potential source of heterogeneity, including age groups, ADRs definitions, ADRs detection methods, study setting, quality of the studies, and sample size, were investigated using sub-group analysis and meta-regression.ResultsThirty-three studies with a total study population of 1,568,164 individuals were included. The pooled prevalence of ADRs in the primary care setting was 8.32% (95% CI, 7.82, 8.83). The percentage of preventable ADRs ranged from 12.35-37.96%, with the pooled estimate of 22.96% (95% CI, 7.82, 38.09). Cardiovascular system drugs were the most commonly implicated medication class. Methods of ADRs detection, age group, setting, and sample size contributed significantly to the heterogeneity of the estimates.ConclusionADRs constitute a significant health problem in the primary care setting. Further research should focus on examining whether ADRs affect subsequent clinical outcomes, particularly in high-risk therapeutic areas. This information may better inform strategies to reduce the burden of ADRs in the primary care setting.
| S-EPMC8153435 | biostudies-literature
Project description:Objective: Deferasirox is an iron-chelating agent prescribed to patients with iron overload. Due to the interindividual variability of deferasirox responses reported in various populations, this study aims to determine the genetic polymorphisms that influence drug responses. Methods: A systematic search was performed from inception to March 2022 on electronic databases. All studies investigating genetic associations of deferasirox in humans were included, and the outcomes of interest included pharmacokinetics, efficacy, and adverse drug reactions. Fixed- and random-effects model meta-analyses using the ratio of means (ROM) were performed. Results: Seven studies involving 367 participants were included in a meta-analysis. The results showed that subjects carrying the A allele (AG/AA) of ABCC2 rs2273697 had a 1.23-fold increase in deferasirox Cmax (ROM = 1.23; 95% confidence interval [CI]:1.06-1.43; p = 0.007) and a lower Vd (ROM = 0.48; 95% CI: 0.36-0.63; p < 0.00001), compared to those with GG. A significant attenuated area under the curve of deferasirox was observed in the subjects with UGT1A3 rs3806596 AG/GG by 1.28-fold (ROM = 0.78; 95% CI: 0.60-0.99; p = 0.04). In addition, two SNPs of CYP24A1 were also associated with the decreased Ctrough: rs2248359 CC (ROM = 0.50; 95% CI: 0.29-0.87; p = 0.01) and rs2585428 GG (ROM = 0.47; 95% CI: 0.35-0.63; p < 0.00001). Only rs2248359 CC was associated with decreased Cmin (ROM = 0.26; 95% CI: 0.08-0.93; p = 0.04), while rs2585428 GG was associated with a shorter half-life (ROM = 0.44; 95% CI: 0.23-0.83; p = 0.01). Conclusion: This research summarizes the current evidence supporting the influence of variations in genes involved with drug transporters, drug-metabolizing enzymes, and vitamin D metabolism on deferasirox responses.
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Project description:BackgroundThis systematic review aims to summarise available patient-reported questionnaires to detect adverse drug reactions (ADRs) that can be utilised by healthcare professionals in clinical practice and to summarise the psychometric properties (validity, reliability, and responsiveness) of the questionnaires.MethodsA systematic literature search was conducted using Medline, Pubmed, Embase, and Emcare databases to screen for articles published between January 2000 and July 2020. Data items regarding validity, reliability, and responsiveness were extracted independently by two authors. The methodological quality was assessed using the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) checklist.ResultsA total of 1563 unique article titles were identified after removing duplicates. Following shortlisting of relevant articles, 19 patient-reported ADR questionnaires were identified. Questionnaires most commonly focused on mental health medications (42.1%, n = 8), followed by general questionnaires applicable to any medication (21.1%, n = 4). Many questionnaires did not report assessing the validity and reliability of the measurement tool. For example, only 11 questionnaires (58%) mentioned assessing content validity, in addition to criterion or construct testing.ConclusionThis systematic review summarised the available patient-reported questionnaires that can be used in research and clinical practice to identify ADRs. Results of this systematic review highlight the need for more robust validity and reliability testing when developing patient-reported ADR questionnaires.
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Project description:Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.
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Project description:Medication-related problems (MRPs) are an important healthcare problem. This study aimed at reviewing the published literature in Ethiopia to estimate the prevalence of MRPs and to summarize associated factors. A comprehensive systematic search was conducted in PubMed, EMBASE, CINAHL, Scopus, Google Scholar, and Google databases from inception to April 2020. Articles that addressed MRPs were eligible for inclusion. Article screening, data extraction, and study quality analysis were performed independently by two reviewers. Studies targeting specific disease condition were considered as specific, while the remaining were nonspecific. The prevalence of MRPs was then computed in medians and interquartile ranges (IQR), while associated factors were summarized in a table. Of the thirty-two studies included in this review, the majority of them (n = 24) targeted MRPs, while the remaining studies (n = 8) investigated adverse drug reactions (ADRs). Studies varied in the study design, study population, and definition of MRPs and ADRs used. The overall median prevalence was 70.8% (IQR = 61.0-80.2) with a range of 16.0% to 88.7%. The median prevalence of MRPs in specific and nonspecific patients was 71.2% (IQR = 60.7-71.2) and 69.3% (IQR = 60.7-82.0), respectively. In addition, a median of 36.6% (IQR = 10.0-85.7) of patients experienced ADRs. Indication-related and effectiveness-related MRPs were commonly reported in both specific and nonspecific patients, while noncompliance MRPs were more prevalent among specific patients than nonspecific patients. Increasing age, presence of co-morbidity, and an increasing number of drugs were the commonly identified contributing factors of MRPs. The review showed that more than two-thirds of the study participants developed MRPs. Hence, an integrated approach should be designed to improve the optimal use of pharmacotherapy to reduce the burden of MRPs. Further, future research should be undertaken to prepare cost-effective and efficient prevention mechanisms to reduce or halt the development of MRPs.
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Project description:BackgroundThe main objective of the present systematic review is to identify potential risk factors for adverse drug reactions (ADRs) through prospective cohort studies in pediatric inpatients.MethodsThe data search was done in the following electronic databases PubMed/MEDLINE; Scopus; LILACS and Web of Science from the earliest record until 31 May 2015. Two reviewers independently screened each study and one of them assessed the methodological quality according to the Newcastle-Ottawa scale for cohort studies. The data extraction was conducted according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative for cohort studies.ResultsThe only risk factor observed in all studies was the increase in the number of prescription drugs. However, other factors were identified, such as the increase in the length of stay or the number of low- or high-risk drugs prescribed, use of general anesthesia and oncological diagnosis. The cumulative incidence of ADR was 16.4% (95% confidence interval: 15.6 to 17.2). The main professional responsible for ADR identification was the pharmacist and the dominant category among the ADRs were gastrointestinal disorders. In addition, analgesics, antibacterial agents and corticosteroids were the drug classes commonly associated with ADRs. The methodology used in this study was tried to homogenize the data extracted; however, this was not sufficient to correct the discrepancies so it was not possible to perform a meta-analysis.ConclusionsThe increase in the number of prescription drugs was the main risk factor in this population. However, additional studies are required to identify the risk factors for ADRs in pediatric inpatients.
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Project description:N-acetyltransferase 2 (NAT2) acetylator status can be classified into three groups depending on the number of rapid alleles (e.g., NAT2*4): rapid, intermediate, and slow acetylators. Such acetylator status may influence the occurrence of adverse drug reactions (ADRs) during sulfasalazine treatment. This systematic review and meta-analysis aimed to evaluate the association between NAT2 acetylator status and ADRs of sulfasalazine. We searched for qualified studies in PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between NAT2 acetylator status and ADRs of sulfasalazine. Nine cohort studies involving 1,077 patients were included in the meta-analysis. NAT2 slow acetylators were associated with an increase in overall ADRs (OR 3.37, 95% CI: 1.43 to 7.93; p = 0.005), discontinuation due to overall ADRs (OR 2.89, 95% CI: 1.72 to 4.86; p < 0.0001), and dose-related ADRs (OR 5.20, 95% CI: 2.44 to 11.08; p < 0.0001), compared with rapid and intermediate acetylators. In conclusion, NAT2 slow acetylators are at risk of ADRs during sulfasalazine treatment. Based on our findings, NAT2 genotyping may be useful to predict the occurrence of ADRs during sulfasalazine treatment.
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