Recent research has linked clozapine, a powerful medication for schizophrenia, to an increased risk of mortality associated with pneumonia and severe gastrointestinal complications.
Clozapine is the only drug in the United States approved to treat “treatment-resistant schizophrenia,” which affects one in five schizophrenic patients. It was removed from global markets in the 1970s due to its association with dangerously low white blood cell counts in 2 percent of users.
Following its approval by the U.S. Food and Drug Administration in 1989, it has been clinically available in the United States since 1990.
A comprehensive analysis of 25 years of patient data revealed that within 20 years of initiating treatment, 30 percent of schizophrenic patients on clozapine developed pneumonia, while 5 percent experienced intestinal blockages.
These complications are reportedly more severe than previously documented and are linked to an increased risk of death, the researchers wrote.
“Clozapine-induced pneumonia and intestinal blockage should be taken as seriously as the white blood cell drop once was,” Dr. Jukka Koskela, leader of the study conducted at the Institute for Molecular Medicine Finland (FIMM) at the University of Helsinki, said in a press release.
The study was recently published in the American Journal of Psychiatry. It was based on data from 2,659 participants with a schizophrenia diagnosis in FinnGen, which tracks electronic health records in Finland.
Participants had an average duration of clozapine use of more than eight years.
Clozapine’s Role in Treating Schizophrenia
The authors of the study tracked the electronic health records of over 30,000 patients over 25 years, with a particular focus on schizophrenic patients and clozapine users.
They identified several serious adverse effects associated with clozapine use, including ileus—a condition in which the gastrointestinal tract malfunctions—seizures, pneumonia, and other respiratory infections.
Clozapine was also linked to low white blood cell counts, Type 2 diabetes, and rapid heart rates. The reasons for these adverse events remain unclear.
The loss of white blood cells may be linked to immune suppression, Dr. Peter Breggin, a psychiatrist, told The Epoch Times. He argues that while clozapine may outperform other medications in suppressing symptoms, it does not address the underlying issues faced by schizophrenic patients, ultimately making them more manageable rather than fundamentally treated.
The medication works by affecting the release of dopamine and serotonin in the brain. Psychiatrists prescribe clozapine because it may improve suicidality, cognition, and mood in patients.
“The use of clozapine is, however, hampered by adverse drug events (ADEs), some of which are life-threatening and have relegated clozapine to a third-line treatment option,” the Finnish researchers wrote.
Clozapine is metabolized in the liver, and some people with genetic variations affecting its breakdown may experience adverse effects.
High concentrations and clozapine metabolites have been linked to seizures, sedation, and excess salivation, the authors wrote. The study revealed that overall, 70 percent of clozapine users experienced at least one adverse event during treatment.
The authors particularly highlighted the link between pneumonia and ileus, which can occur years after initiating clozapine use. Both conditions are also significantly linked with increased mortality.
Having ileus more than quadrupled the risk of death among clozapine users, while pneumonia tripled the odds of mortality.
The prolonged follow-up period of the study allowed for a more accurate assessment of clozapine’s side effects, Dr. Juulia Partanen, a research physician at FIMM and study co-author, said in the press release.
“Previous studies have mainly identified side effects that occur shortly after starting the medication,” she said.
The research was funded by several institutions, including the Doctoral Program in Population Health at the University of Helsinki, the Finnish Medical Foundation, the Swedish Society for Medical Research, the Academy of Finland, and the Academy of Finland Center of Excellence in Complex Disease Genetics.
