Elevated clozapine levels associated with infection: A systematic review

Clark, Scott; Warren, Nicola; Kim, Gajin; Jankowiak, David; Schubert, Klaus Oliver; Kisely, Steve; Forrester, Tori; Baune, Bernhard T.; Siskind, Dan

doi:10.1016/j.schres.2017.03.045

Cited by 117 publications

(96 citation statements)

References 60 publications

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“…In addition, intracellular germ cell lung disease is known to cause hyponatremia (SIADH) as can also be the case with serotonergic antidepressants. In addition, in case of fever, tolerance towards antipsychotic drugs may be impaired, especially clozapine (24). Finally, COVID-19 causes a respiratory syndrome, which may be aggravated by psychotropic drugs that depress the respiratory system (benzodiazepine, carbamates, opioids).…”

Section: Individual Vulnerability Of Psychiatric Patients To Coronavirusmentioning

confidence: 99%

Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review

et al. 2020

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Objective: The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France. Methods: The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France. Results : We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: 1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; 2) age (the elderly form the population most vulnerable to the coronavirus); 3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and 4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of "COVID+ units". These units are under the dual supervision of a psychiatrist and an internist / infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical checkups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies;developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role...

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Section: Individual Vulnerability Of Psychiatric Patients To Coronavirusmentioning

confidence: 99%

Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review

et al. 2020

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“…9 Through 2016, there are 40 published cases of clozapine elevation during infections. 10 There are also published clozapine intoxications during severe inflammation without infection. 11 More recently, in a Beijing hospital, three cases of clozapine intoxication we identified included ones with pneumonia, 12 influenza 11 and dermatitis in the absence of infection.…”

Section: Inflammation Can Increase Clozapine Levelsmentioning

confidence: 99%

“…(1) no clinically relevant effects on the serum clozapine concentrations in the 11% of infection episodes which presented with no leukocytosis or CRP elevations; (2) halving the clozapine dose would be advisable in 61% of the infection episodes; and (3) reducing the clozapine dose to one-third would be advisable in 28% of infection episodes. 13 Therefore, based on the US 8 14 and Chinese experiences [11][12][13] as well as on the literature, 10 we proposed that clinicians need to be very alert regarding clozapine patients' risk of clozapine intoxications during any kind of systemic inflammation associated with fever and/or CRP elevations. Until better data is available, based on our experience in the US and China, we have developed three sets of recommendations regarding infection, based on timeframe: (1) prevention; (2) during the infection; and (3) after the infection.…”

Section: Inflammation Can Increase Clozapine Levelsmentioning

confidence: 99%

Clozapine is strongly associated with the risk of pneumonia and inflammation

et al. 2020

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Clinicians need to remember that (1) systemic inflammations can increase clozapine level; (2) clozapine, by itself, can cause inflammation, particularly during titration that is too rapid for that patient; (3) clozapine may increase the risk of infection; and (4) more specifically, clozapine may be particularly strongly associated with the risk of pneumonia. Pneumonia appears to be associated with high mortality in clozapine patients around the world. Clinicians who are alert to the risk of pneumonia in clozapine patients may significantly decrease mortality in clozapine patients. There is no data on COVID-19 infections in clozapine patients, but based on what we know about clozapine pharmacology, we can hypothesise that clozapine, possibly by impairing immunological mechanisms, may increase the risk of pneumonia in infected patients. More importantly, once fever and/or pneumonia develops, the clozapine dose should be cut in half to decrease the risk of clozapine intoxication. If there is any doubt that in spite of halving the dose there are still signs of clozapine intoxication, completely stopping clozapine may be indicated. Once the signs of inflammation and fever have disappeared, the clozapine dose can be increased to the prior dosage level.

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“…Elle est d'autant plus marquée que la durée de traitement par la clozapine est longue et ne semble pas être dose dépendante [6,7]. Il est toutefois important de souligner les nombreux rapports de cas, associant dose élevée de clozapine et infection sévère [8]. La survenue de ces infections se complique en retour d'une élévation des concentrations plasmatiques de la clozapine par inhibition des cytochromes 1A2 et 3A4 par les médiateurs de l'inflammation (TNF␣, IL-6 et CRP) entraînant hypersédation et confusion mentale [9].…”

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