Clozapine (brand names Clozaril® and FazaClo®) was the first of many atypical antipsychotics, or, what are sometimes referred to as second generation neuroleptics, to be developed over the past many years. Although it has been around since 1959, it wasn’t approved by the FDA until 1989. This particular antipsychotic is also a tricyclic dibenzodiazepine.

It is primarily used to treat schizophrenia and other psychiatric disorders after treatment with other antipsychotics have either proven to be ineffective or have had side effects which the patient could not tolerate.

What it’s used to treat

Clozapine is effective in treating schizophrenia. It helps to control and alleviate the positive symptoms, which include delusions, hallucinations, anger, and bizarre behaviors. Unlike typical antipsychotics, clozapine also can effectively treat the negative symptoms of schizophrenia, such as flat affect, inability to initiate or carry out goal-oriented tasks and activities, catatonic behaviors, and thought and speech difficulties.

Clozapine is also used at times to treat mania, which is a symptom of bipolar disorder as well as schizoaffective disorder. However, it is not licensed for the treatment of mania.

Because of a potentially life-threatening side affect called agranulocytosis, in which white blood cells significantly decrease, individuals who take clozapine must have their blood checked prior to beginning treatment with clozapine, and then monitored regularly. During the first 6 months to one year, this must be done weekly. After that, their blood can be tested every two weeks. This makes clozapine a very inconvenient medication for many individuals.

How it works

The pharmacological makeup of clozapine is unique compared to other antipsychotics. Not only is it a serotonin antagonist, it also blocks receptors for dopamine, acetylcholine, norepinephrine, and histamine. Since dopamine is believed to play a significant role in schizophrenia, clozapine thus helps to control and alleviate psychotic symptoms.

How it’s administered

Clozapine comes in tablet form and is taken orally one to three times a day.

Potential Side Effects

Although clozapine is very effective in the treatment of schizophrenia, it has many potential side affects, including agranulocytosis (mentioned above), which affects just under one percent of patients. 1 Other, more common, side effects include:

  • Increase in saliva
  • Significant and fast weight gain
  • Vertigo
  • Orthostatic hypotension
  • Nausea and vomiting
  • Insomnia
  • Constipation
  • Digestive problems

A potentially serious side effect of clozapine is called metabolic syndrome. This actually involves several conditions which increase the chance of diabetes, heart disease, and stroke.2 Myocarditis, which involves inflammation of the heart, is another a potentially fatal side effect of Clozapine. And clozapine may cause neuroleptic malignant syndrome, which can be fatal.

Clozapine may also make a person more prone to hyperglycemia.3 The literature is mixed with regards to whether or not clozapine can cause tardive dyskinesia, which is associated with many antipsychotic medications.


Clozapine can be especially risky for individuals with a history of congestive heart failure, heart disease, seizures or epilepsy, nursing women, elderly individuals with dementia, arrhythmias, diabetes, enlarged prostrate, and diabetes to name several. You should tell your doctor if you are pregnant or have any other medical conditions.

  1. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States, New England Journal of Medicine, 1993
  2. Most effective antipsychotic drug has serious health consequences, July 2006
  3. Clozaril (clozapine tablets), April 2004

written by Dr. Cheryl Lane, PsyD