Taking Steps to Prevent Pneumonia Could Reduce Risk of Death Associated With Clozapine

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Deaths related to the use of the antipsychotic clozapine—already associated with a lower number of deaths than other antipsychotics—could be further reduced by better awareness among clinicians, patients, and families of the risk for pneumonia associated with aspiration (inhalation of saliva).

So say Jose De Leon, M.D., of the Mental Health Research Center at Eastern State Hospital, in Lexington, Ky., and colleagues in an editorial in Schizophrenia Bulletin.

They reviewed data from VigiBase, the global database of the World Health Organization (WHO), which showed that a high percentage of deaths among people who took clozapine were from pneumonia.

Clozapine is widely underprescribed despite a large body of evidence that it is the most effective antipsychotic, especially for patients who have not responded adequately to other treatments, according to the authors. Moreover, a recent meta-analysis also published in Schizophrenia Bulletin found that patients continuously treated with clozapine had a significantly lower mortality rate compared with patients on other antipsychotics.

Vigibase includes 20 million reports of spontaneously reported adverse drug reactions from the drug agencies of 134 countries. De Leon and colleagues searched the database for reports of adverse drug reactions associated with clozapine. They found 4,951 reports of pneumonia during clozapine treatment; 1,654 involved patient deaths. This was the highest of all clozapine-related deaths, indicating that when death related to clozapine occurs (which is relatively rare) there is a 33% chance that pneumonia will be the cause.

“The association between clozapine and increased risk of pneumonia is partly explained because all antipsychotics can interfere with swallowing, increasing the potential for aspiration,” they wrote. “The potential for aspiration and aspiration pneumonia during antipsychotic treatment may be further increased by sedation and hypersalivation. As clozapine is more prone to cause sedation and hypersalivation than other antipsychotics, it is not surprising that it may be more strongly associated with pneumonia.”

To decrease deaths associated with pneumonia, De Leon and colleagues offer the following recommendations for medical professionals:

  • Use lower doses of clozapine when possible to decrease risk of hypersalivation, sedation, and swallowing disturbances.
  • Educate patients and their families about the risk of pneumonia with clozapine use so they know to contact their clinician when infection occurs.
  • Decrease dosage of clozapine when the patient has pneumonia.

William Carpenter, M.D., editor of Schizophrenia Bulletin, reiterated that clozapine is underused and emphasized that the drug does not place patients at greater risk for death compared with other antipsychotic medications. “Using minimally effective dosing may reduce this risk, and reduction of clozapine dosing during infection should be considered,” he said.

For related information, see the Psychiatric News article “Experts Brainstorm How to Expand Clozapine Use.”

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