Dataset Information

Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.

ABSTRACT: 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.

SUBMITTER: Skokou M

PROVIDER: S-EPMC9317288 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.

Skokou Maria M Karavia Eleni A EA Drakou Zoi Z Konstantinopoulou Vassiliki V Kavakioti Christina-Anna CA Gourzis Philippos P Kypreos Kyriakos E KE Andreopoulou Ourania O

Pharmaceuticals (Basel, Switzerland) 20220701 7

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, ther ...[more]

PMID: 35890117

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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.

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.

Project description:BackgroundIdentification of real-time adverse drug reactions [ADRs] (as opposed to the risk of ADRs) in older poly-medicated people in primary care is a challenging task, often undertaken without an explicit strategy. This systematic review aims to evaluate replicable instruments and methods for identifying and addressing ADRs.MethodsA systematic search was conducted in Medline, CINAHL, Scopus, Web of Science and Cochrane library, using controlled vocabulary (MeSH) and free-text terms. Randomised controlled trials (RCTs) implementing strategies to identify or resolve ADRs experienced by patients in primary care were included. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool. Discrepancies were resolved by discussion.ResultsFrom 2,182 unique records, 49 studies were identified for full review. Eight papers reporting results from 6 RCTs were included. All six trials utilised a list of medicine-related unwanted symptoms to identify ADRs. Two of three studies using adverse drug reaction questionnaires reported statistically significant increased rates of ADR reporting. Two of three studies that combined symptom questionnaires with prescriber consultations reported reductions in the number of health problems. Overall, results suggest that the three studies that described multidisciplinary collaborations using lists of ADRs plus prescriber reviews enhanced patient safety. However, the RCTs were unblinded and reported suboptimal retention. When considered as a whole, findings are equivocal and the data are too heterogenous to warrant any firm conclusions, beyond the need for more research to optimise strategies to safeguard patient wellbeing.ImplicationsAdaptable and scalable instruments with decision support are needed in primary care to identify and mitigate medicine-related harm in older poly-medicated people. The effectiveness of adverse drug reaction identification instruments, the value of comprehensive instruments, and the optimum method of delivery should be explored in multicentre trials.

Dataset Information

Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.

Publications

Adverse Drug Reactions in Relation to Clozapine Plasma Levels: A Systematic Review.

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