November 13, 2024

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Clozapine Tied to Higher Risk of GI Issues and Pneumonia

Clozapine Tied to Higher Risk of GI Issues and Pneumonia



Clozapine Tied to Higher Risk of GI Issues and Pneumonia

AJP Study: 25-Year Follow-Up Shows Higher Than Expected Risk of Gastrointestinal Issues and Pneumonia in Schizophrenia Patients Using Clozapine!

Clozapine is a commonly prescribed medication for treatment-resistant schizophrenia and is often the only effective treatment for about one-fifth of patients with the disorder. It also helps reduce mortality risk and is the only drug approved to prevent suicide in individuals with schizophrenia.

However, the use of clozapine is limited by adverse drug events (ADEs). In addition to common side effects like drowsiness, excessive salivation, constipation, and weight gain, clozapine can cause more severe, potentially fatal reactions, such as agranulocytosis, seizures, myocarditis, intestinal obstruction, and pneumonia.

Accurate risk prediction and effective management strategies for ADEs are crucial for the safe use of clozapine. To address the limitations of previous clinical studies—such as small sample sizes and short follow-up periods—a team from the Institute for Molecular Medicine Finland (FIMM) conducted a long-term analysis of clozapine’s adverse effects using data from Finland’s biobank.

The study followed more than 2,600 clozapine users over 25 years. It identified five main health issues during clozapine treatment: gastrointestinal motility disorders, seizures, pneumonia, other acute respiratory infections, and tachycardia. Among them, severe gastrointestinal motility issues, such as intestinal obstruction, had a cumulative incidence rate of 5.3%, while pneumonia had a rate of 29.5%. These conditions were associated with a 350% and 180% increased risk of death, respectively.

The findings were published in The American Journal of Psychiatry.

 

Clozapine Tied to Higher Risk of GI Issues and Pneumonia

 

The study involved data from 321,302 participants, of which 3,202 had records of clozapine use, and 2,659 were diagnosed with schizophrenia. The median duration of clozapine use was 8.4 years, with a median follow-up period of 12.7 years.

Compared to patients with schizophrenia not using clozapine, 27 distinct diseases and health-related events were significantly more prevalent among clozapine users (n=2187). A cluster analysis identified five primary categories of conditions: gastrointestinal motility disorders, seizures, pneumonia, other acute respiratory infections, and tachycardia. Critical events requiring immediate treatment included drug-induced neutropenia, seizures, and pneumonia. Chronic conditions, such as type 2 diabetes, were also common.

A total of 69.9% of clozapine users (1,529 out of 2,187) experienced at least one of the above-mentioned health events. Specifically, 717 patients developed tachycardia, 453 experienced seizures, 421 developed type 2 diabetes, and 408 were diagnosed with pneumonia. Women had a higher risk of constipation, acute upper respiratory infections, intestinal infections, and type 2 diabetes.

A comparison of health event rates 10 years before and 20 years after starting clozapine showed that clozapine use accelerated the occurrence of ADEs. After 20 years, the cumulative incidence rates for pneumonia, constipation, type 2 diabetes, and intestinal obstruction were 29.5%, 22.7%, 33.4%, and 5.3%, respectively. Most of these events occurred more than six months after initiating clozapine.

By age 50, the cumulative incidence of pneumonia, constipation, type 2 diabetes, seizures, and tachycardia exceeded 25% among clozapine users. By age 70, the rates for these events surpassed 50%, reaching 69.0%, 57.2%, 54.5%, 73.4%, and 76.5%, respectively.

The study also found a strong association between the occurrence of these events and increased mortality risk among clozapine users. Intestinal obstruction was linked to a 350% increased risk of death, while pneumonia raised the risk by 180%. The median time from the last ADE to death was 6.8 months for intestinal obstruction and 1.8 months for pneumonia.

For safer clozapine use, the development of clinical markers that can predict ADEs is essential. The researchers evaluated the impact of 10 genes related to clozapine metabolism on these events. Reduced activity of the enzymes CYP2C19 and CYP1A2 was associated with a higher risk of pneumonia during clozapine use.

Overall, this extensive study highlighted the significant burden of intestinal obstruction and pneumonia in clozapine-treated schizophrenia patients. It also underscored the role of CYP enzymes in influencing pneumonia risk.

Clozapine Tied to Higher Risk of GI Issues and Pneumonia

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(source:internet, reference only)


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