International Variation in Clozapine Hematologic Monitoring—A Call for Action

Oloyede, Ebenezer; Taylor, David; MacCabe, James H.

doi:10.1001/jamapsychiatry.2023.0376

Cited by 9 publications

(1 citation statement)

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“…Recently, however, this danger has been assumed to be lower. 34 Nevertheless, respiratory symptoms, marked sedation with a tendency to fall, and epileptic seizures, as observed in our series, must also be carefully considered. 35 We have observed further serious side effects, especially severe sedation with motor unsteadiness and associated tendency to fall, intermittent pulmonary infections, febrile episodes that may be associated with hypersalivation and possible aspiration, and in one patient a seizure; however, neither agranulocytosis nor delirium were noted.…”

Section: Discussionmentioning

confidence: 75%

Clozapine for the treatment of aggressiveness and agitation in advanced dementia

Michael,

Erfurth

et al. 2023

Psychogeriatrics

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BackgroundDistressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context.MethodsIn a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail.ResultsA total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores.ConclusionsIn summary, clozapine was effective and well tolerated in 23 patients, suggesting that low‐dose clozapine may help to alleviate the suffering of difficult‐to‐treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment.

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Section: Discussionmentioning

confidence: 75%

Clozapine for the treatment of aggressiveness and agitation in advanced dementia

Michael,

Erfurth

et al. 2023

Psychogeriatrics

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A systematic review of clozapine‐associated inflammation and related monitoring

Leung,

Zhang,

Markota

et al. 2023

Pharmacotherapy

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Clozapine is an effective antipsychotic medication used for treatment‐resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life‐threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6,915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: i) the impact of clozapine on inflammatory markers, ii) monitoring cardiac and other organ function during clozapine‐associated inflammatory processes, and iii) monitoring non‐specific signs and symptoms of inflammation. Elevated levels of C‐reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4 to 8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically‐relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine‐associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence‐based guidelines for the monitoring of clozapine‐associated inflammation.

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