The haematological side effects of clozapine: literature review and meta-analysis
Bibliographic record
Abstract
Aims This review and meta-analysis aim to estimate the cumulative incidence of clozapine induced agranulocytosis and leukopenia the impact of the associated factors such as dose of clozapine, duration of follow-up, gender and race on the cumulative incidence. Background Clozapine is the only medication licensed for treatment-resistant schizophrenia. There has been a renewed interest in the role of Clozapine in the treatment of Schizophrenia based on strong evidence that favours its efficacy and safety. Despite the evidence that Clozapine has superior efficacy and has been recommended for treatment-resistant cases by the national guidelines, the drug is underutilised. Method We included all studies in which clozapine was used for a psychotic illness. We included studies which provided data on two primary indices; Leucopenia or agranulocytosis and neutropenia; defined according to the cut off used by CPMS for total WBC and neutrophil count. Additionally we included studies reporting another blood dyscrasia or death due to agranulocytosis. Studies were identified by searching AMED, BIOSIS, CINAHL, EMBASE, MEDLINE, PsycINFO, PubMed, and registries of Clinical Trials and their monthly updates, hand searches, gray literature, and conference proceedings from the first available date until 2nd February, 2015. The search was updated on 15th March, 2017. The Protocol was initiated and then registered with PROSPERO International prospective register of systematic reviews University of York, Centre for Reviews and Dissemination. Result The cumulative incidence of the agranulocytosis in all studies was 00.32 % (CI 00.1-0.63). The cumulative incidence in all studies for different types of blood dyscrasia were following: leucopenia 00.96 % (CI 0.39-1.70), neutropenia 2.93 % (CI 1.49-4.72), other blood dyscrasias 4.64% (CI 2.34-7.52) and any blood dyscrasia was 2.23 (CI 1.46-3.12). Conclusion The limitations of this review are mainly due to the nature of evidence from the included studies. We adopted a broad inclusion criteria to include all the available evidence. Number of patients started on Clozapine may be withdrawn from the Clozapine on the earliest signs of blood dyscrasias since the introduction of Clozapine monitoring services. This means that the true incidence of agranulocytosis and neutropenia may be higher and this may be a major bias in finding the true incidence of Clozapine induced neutropenia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.031 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.022 | 0.041 |
| Bibliometrics | 0.009 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".