Clozapine's side effect

Clozapine is an atypical antipsychotic medication used in the treatment of schizophrenia, and is also sometimes used off-label for the treatment of bipolar disorder. The first of the atypical antipsychotics to be developed, it was first introduced in Europe in 1971, but was voluntarily withdrawn by the manufacturer in 1975 after it was shown to cause agranulocytosis, a condition involving a dangerous decrease in the number of white blood cells, that led to death in some patients. In 1989 after studies demonstrated that it was effective in treating treatment-resistant schizophrenia. the United States Food and Drug Administration (FDA) approved the use of clozapine solely for that use, requiring regular white blood cell and absolute neutrophil counts. The FDA also requires clozapine to carry five black box warnings for agranulocytosis, seizures, myocarditis, for "other adverse cardiovascular and respiratory effects", and for "increased mortality in elderly patients with dementia-related psychosis."In 2002 the FDA approved clozapine for reducing the risk of suicidal behavior for patients with schizophrenia.




Clozapine may cause a severe reduction in white blood cell count, a condition known as agranulocytosis, in approximately 1 in 100 patients who take it for at least one year. White blood cells fight infections, and a severe reduction in white blood cells can result in severe infections. If not caught early, agranulocytosis can be fatal. Therefore, the white blood cell count should be measured (with a blood test) prior to starting treatment and regularly (weekly) while patients receive this medication, and for 4 weeks after it is stopped.


Among elderly patients with dementia-related psychosis, treatment with clozapine is associated with an increased risk of death for unclear reasons. Clozapine is not approved for use in dementia-related psychosis.


Seizures have occurred in approximately 1 of every 20 to 30 persons receiving clozapine. Patients receiving higher doses seem to be at higher risk.


Dizziness may occur in 1 of 5 persons taking clozapine. In some cases this may be due to orthostatic hypotension, a marked decrease in blood pressure that occurs when going from a lying or sitting position to a standing position. The drop in blood pressure may lead to loss of consciousness or even cardiac and respiratory arrest. This reaction is more common during the first few weeks of therapy while the dose is increasing, when drug is stopped briefly, or when patients are taking benzodiazepines such asdiazepam (Valium) or other anti-psychotic drugs.


The most common side effect of clozapine is drowsiness. Other side effects include increased heart rate, increased salivation, headache, tremor, low blood pressure, and fever. Clozapine has anticholinergic effects that interfere with the function of smooth muscles. This can lead to blurred visionand difficulty urinating (when there is enlargement of the prostate) due to effects on the muscles of the eye and bladder. Clozapine slows the intestine and leads to constipation in approximately 14% of patients. Paralysis of the intestinal muscles can lead to paralytic ileus, a condition in which the intestine stops working.