Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine

Leung, Jonathan G.; Hasassri, M. Earth; Barreto, Jason N.; Nelson, Sarah; Morgan, Robert J.

doi:10.1016/j.psym.2016.11.013

Cited by 32 publications

(23 citation statements)

References 40 publications

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“…Ten studies were reviews/meta-analyses [ 1 , 13 , 18 , 27 , 41 – 46 ], while other studies included 12 case reports [ 47 – 58 ]and one letter to the editor[ 15 ]. Most of the literature concerned patients aged 65 and older [ 1 , 4 , 6 , 8 – 10 , 12 , 18 , 35 , 38 , 41 , 45 , 47 , 49 , 51 ] while others investigated an adult population with bipolar/schizophrenic disorders [ 26 , 36 , 37 , 40 , 48 , 50 , 55 , 56 , 59 ]. No randomized clinical trials (RCTs) were identified, but one meta-analysis of 6 RTCs was found [ 27 ]( S2 Fig ).…”

Section: Resultsmentioning

confidence: 99%

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

et al. 2017

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IntroductionAntipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined.AimThe aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia.MethodsA search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia.ResultsThe literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR.ConclusionInnovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.

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Section: Resultsmentioning

confidence: 99%

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

et al. 2017

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“…2 Although clozapine reduces overall mortality in severe schizophrenia, 3 it is associated with a number of often poorly understood side-effects with a growing body of evidence linking clozapine with elevated rates of pneumonia-related admission and mortality. [4][5][6][7][8][9] Mortality from respiratory infections/sepsis despite intensive monitoring is a common reason for discontinuing treatment. 10,11 Various mechanisms for the increase in pneumonia have been suggested, including aspiration, sialorrhoea and impairment of swallowing function with oesophageal dilatation and hypomotility as well as agranulocytosis 12 and smoking.…”

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confidence: 99%

Clozapine is associated with secondary antibody deficiency

et al. 2018

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Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.Declaration of interestS.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.

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“…CLZ-associated secondary antibody deficiency was only recently described [ 170 , 171 , 172 , 173 ]. CLZ-associated hypogammaglobulinemia was recently described as a treatable cause of sinopulmonary infection susceptibility [ 170 , 171 , 172 , 173 ]. A model disease for elucidating the mechanism of CLZ-induced secondary immune deficiency syndrome was already identified.…”

Section: Candidate Pathomechanisms Of Clz Associated With Cx43mentioning

confidence: 99%

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

Okada

Fukuyama

Shiroyama

et al. 2020

IJMS

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Clozapine (CLZ) is an approved antipsychotic agent for the medication of treatment-resistant schizophrenia but is also well known as one of the most toxic antipsychotics. Recently, the World Health Organization’s (WHO) global database (VigiBase) reported the relative lethality of severe adverse reactions of CLZ. Agranulocytosis is the most famous adverse CLZ reaction but is of lesser lethality compared with the other adverse drug reactions of CLZ. Unexpectedly, VigiBase indicated that the prevalence and relative lethality of pneumonia, cardiotoxicity, and seizures associated with CLZ were more serious than that of agranulocytosis. Therefore, haematological monitoring in CLZ patients monitoring system provided success in the prevention of lethal adverse events from CLZ-induced agranulocytosis. Hereafter, psychiatrists must amend the CLZ patients monitoring system to protect patients with treatment-resistant schizophrenia from severe adverse CLZ reactions, such as pneumonia, cardiotoxicity, and seizures, according to the clinical evidence and pathophysiology. In this review, we discuss the mechanisms of clinical efficacy and the adverse reactions of CLZ based on the accumulating pharmacodynamic findings of CLZ, including tripartite synaptic transmission, and we propose suggestions for amending the monitoring and medication of adverse CLZ reactions associated with pneumonia, cardiotoxicity, and seizures.

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Characterization of Admission Types in Medically Hospitalized Patients Prescribed Clozapine

Cited by 32 publications

References 40 publications

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

Clozapine is associated with secondary antibody deficiency

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

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