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
Publications
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.
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Project description:Adverse 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.We 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.There 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: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.
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