# Reliability of tachycardia as an early warning sign in acute clozapine-induced cardiac inflammation: Protocol for a systematic review

**Authors:** James Richard O’Neill, Prakruti Babu Narendra Prasad, Matthew Croft, Matthew Manton, Natalie King, Daniel Romeu

PMC · DOI: 10.1371/journal.pone.0341729 · PLOS One · 2026-02-25

## TL;DR

This study will review the reliability of tachycardia as an early warning sign for clozapine-induced cardiac inflammation in people with psychosis.

## Contribution

The study is the first systematic review to evaluate tachycardia's diagnostic accuracy for detecting clozapine-induced cardiac inflammation.

## Key findings

- Tachycardia may have high sensitivity but poor specificity for detecting CICI.
- The review will synthesize existing literature to assess the effectiveness of tachycardia as an early warning sign.
- Findings will be shared with clinicians and researchers to improve detection practices.

## Abstract

Clozapine-induced cardiac inflammation (CICI) can have serious consequences for people with psychosis and can be fatal if not detected in a timely manner. The best available methods of investigation for CICI are resource-intensive, whereas clinical practice often utilises cheaper and more practical methods of detection such as history, examination, and blood tests. Heart rate monitoring is commonly used as an early-warning sign in detecting potential CICI. Previous studies have found that, although this has a high sensitivity, it has poor specificity. As far as we are aware, no systematic review has investigated the role of tachycardia as a detection tool for CICI.

Systematic diagnostic test accuracy review of the available literature will be used to assess the effectiveness of tachycardia as an early-warning sign for CICI. We will search eight electronic databases and grey literature using a comprehensive and systematic approach. Grey literature sources will include conference proceedings and professional guidance documents identified through expert consultations. Retrieved articles will be critically appraised, synthesised, and meta-analysed, where data permit.

This systematic review will use data from existing studies, hence no ethical approvals are required. Findings will be disseminated to academic colleagues through a peer-reviewed publication and relevant academic meetings, and to clinicians through distribution to local and national clinical networks.

PROSPERO registration ID: CRD42025650379

## Linked entities

- **Chemicals:** clozapine (PubChem CID 135398737)
- **Diseases:** psychosis (MONDO:0005485)

## Full-text entities

- **Genes:** IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** Tachycardia (MESH:D013610), chest pain (MESH:D002637), cardiomyopathy (MESH:D009202), pneumonia (MESH:D011014), Myocarditis (MESH:D009205), Fever (MESH:D005334), conditions (MESH:D020763), CICI (MESH:D007249), myopericarditis (MESH:D010146), coronary heart disease (MESH:D003327), muscle (MESH:D019042), shortness of breath (MESH:D004417), psychiatric (MESH:D001523), heart failure (MESH:D006333), hypersensitivity (MESH:D004342), Pericarditis (MESH:D010493), postural orthostatic tachycardia (MESH:D054972), infection (MESH:D007239), psychosis (MESH:D011618)
- **Chemicals:** Clozapine (MESH:D003024), sodium valproate (MESH:D014635)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935219/full.md

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Source: https://tomesphere.com/paper/PMC12935219