Clozapine-Related Negative Myoclonus Associated With Urinary Tract Infection

Takahashi, Tetsuya; Masuya, Y.; Ueno, Kanji; Watanabe, Kyohei; Takahashi, Masahiro; Morita, Machiyo; Higashima, Masato; Wada, Yuji

doi:10.1097/jcp.0000000000000290

Cited by 9 publications

(15 citation statements)

References 15 publications

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“…8 Most of these patients were managed with a reduction in their dose of clozapine during the acute infection; however, some were able to stay on or reach their preinfection dose of clozapine with no recurrence in negative myoclonus. [8][9][10][11] In contrast, our patient had no evidence of infection, nor did she have a supratherapeutic clozapine plasma level.…”

Section: Discussioncontrasting

confidence: 55%

Case of Clozapine-Associated Negative Myoclonus

Rodin

Evans

2023

J Clin Psychopharmacol

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Section: Discussioncontrasting

confidence: 55%

Case of Clozapine-Associated Negative Myoclonus

Rodin

Evans

2023

J Clin Psychopharmacol

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“…CYP downregulation was also demonstrated as a consequence of sufficient inflammation and significant temperature elevation ( Elin et al, 1975 ). Therefore, caution should be exercised in case of infection when administering CYP substrates, as this may result in toxicity and ADRs ( Vozeh et al, 1978 ; Blumenkopf and Lockhart, 1983 ; Levine and Jones, 1983 1 ; Raaska et al, 2002 ; Haack et al, 2003 ; de Leon and Diaz, 2003 ; Jecel et al, 2005 ; Darling and Huthwaite, 2011 ; Espnes et al, 2012 ; Kwak et al, 2014 ; Leung et al, 2014 ; Takahashi et al, 2015 ; Clark et al, 2018 ; Khan and Khan, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…Early works assessed the effect of an infection induced intentionally by lipopolysaccharides (LPS) injection on antipyrine pharmacokinetics, and several studies have assessed the impact of infection on psychotropic agents (clozapine, risperidone). The increase of clozapine levels, a CYP1A2 substrate, due to inflammation has been well studied and demonstrated ( Raaska et al, 2002 ; Haack et al, 2003 ; de Leon and Diaz, 2003 ; Jecel et al, 2005 ; Pfuhlmann et al, 2009 ; Darling and Huthwaite, 2011 ; Espnes et al, 2012 ; Abou Farha et al, 2012 ; Leung et al, 2014 ; Kwak et al, 2014 ; Takahashi et al, 2015 ; ten Bokum et al, 2015 ; Hefner et al, 2016 ; Ruan et al, 2017 ; Clark et al, 2018 ; Ruan et al, 2018 ; Ruan et al, 2020 ). A positive and significant correlation between clozapine and CRP levels ( r = 0.313, p < 0.01) was found, with a 2- to 6-fold increase in serum levels and the development of toxic symptoms, as well as improvement after dose reduction or infection recovery ( Raaska et al, 2002 ; Haack et al, 2003 ; de Leon and Diaz, 2003 ; Jecel et al, 2005 ; Pfuhlmann et al, 2009 ; Darling and Huthwaite, 2011 ; Espnes et al, 2012 ; Kwak et al, 2014 ; Leung et al, 2014 ; Takahashi et al, 2015 ; ten Bokum et al, 2015 ; Hefner et al, 2016 ; Abou Farha et al, 2012 ; Ruan et al, 2017 ; Clark et al, 2018 ; Ruan et al, 2018 ; Ruan et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…The increase of clozapine levels, a CYP1A2 substrate, due to inflammation has been well studied and demonstrated ( Raaska et al, 2002 ; Haack et al, 2003 ; de Leon and Diaz, 2003 ; Jecel et al, 2005 ; Pfuhlmann et al, 2009 ; Darling and Huthwaite, 2011 ; Espnes et al, 2012 ; Abou Farha et al, 2012 ; Leung et al, 2014 ; Kwak et al, 2014 ; Takahashi et al, 2015 ; ten Bokum et al, 2015 ; Hefner et al, 2016 ; Ruan et al, 2017 ; Clark et al, 2018 ; Ruan et al, 2018 ; Ruan et al, 2020 ). A positive and significant correlation between clozapine and CRP levels ( r = 0.313, p < 0.01) was found, with a 2- to 6-fold increase in serum levels and the development of toxic symptoms, as well as improvement after dose reduction or infection recovery ( Raaska et al, 2002 ; Haack et al, 2003 ; de Leon and Diaz, 2003 ; Jecel et al, 2005 ; Pfuhlmann et al, 2009 ; Darling and Huthwaite, 2011 ; Espnes et al, 2012 ; Kwak et al, 2014 ; Leung et al, 2014 ; Takahashi et al, 2015 ; ten Bokum et al, 2015 ; Hefner et al, 2016 ; Abou Farha et al, 2012 ; Ruan et al, 2017 ; Clark et al, 2018 ; Ruan et al, 2018 ; Ruan et al, 2020 ). Further investigations are needed concerning anticoagulant therapy, as only one case of severe bleeding in the context of infection was reported in the literature ( Blumenkopf and Lockhart, 1983 ).…”

Section: Resultsmentioning

confidence: 99%

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Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature

et al. 2021

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Background: Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activity via multiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to review the current published data on the impact of inflammation on CYP activities in adults to support drug individualization based on comorbidities and diseases in clinical practice.Methods: This systematic review was conducted in PubMed through 7th January 2021 looking for articles that investigated the consequences of inflammation on CYP activities in adults. Information on the source of inflammation, victim drugs (and CYPs involved), effect of disease-drug interaction, number of subjects, and study design were extracted.Results: The search strategy identified 218 studies and case reports that met our inclusion criteria. These articles were divided into fourteen different sources of inflammation (such as infection, autoimmune diseases, cancer, therapies with immunomodulator…). The impact of inflammation on CYP activities appeared to be isoform-specific and dependent on the nature and severity of the underlying disease causing the inflammation. Some of these drug-disease interactions had a significant influence on drug pharmacokinetic parameters and on clinical management. For example, clozapine levels doubled with signs of toxicity during infections and the concentration ratio between clopidogrel’s active metabolite and clopidogrel is 48-fold lower in critically ill patients. Infection and CYP3A were the most cited perpetrator of inflammation and the most studied CYP, respectively. Moreover, some data suggest that resolution of inflammation results in a return to baseline CYP activities.Conclusion: Convincing evidence shows that inflammation is a major factor to be taken into account in drug development and in clinical practice to avoid any efficacy or safety issues because inflammation modulates CYP activities and thus drug pharmacokinetics. The impact is different depending on the CYP isoform and the inflammatory disease considered. Moreover, resolution of inflammation appears to result in a normalization of CYP activity. However, some results are still equivocal and further investigations are thus needed.

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“…[1][2][3][4][5] Adverse effects attributed to elevated plasma concentrations of clozapine include somnolence, confusion, disorientation, dizziness, aphasia and extrapyramidal symptoms. [1][2][3][4][5] Apart from UTIs, this phenomenon has also been reported in association with other infectious processes and with tissue injury, 1,6-9 sometimes without clozapine-associated adverse effects. 10 The mechanism implicated in increasing plasma concentrations of clozapine and norclozapine is not believed to be related to the exposure to the pathogen or the damage to the tissue, but rather the effects of cytokines released in response to proinflammatory events, such as those mentioned above.…”

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confidence: 99%