21 Facts About Clozapine

Clozapine is a psychiatric medication and is the first atypical antipsychotic .

Clozapine is regarded as the gold-standard treatment when other medication has been insufficiently effective and its use is recommended by multiple international treatment guidelines, after resistance to earlier neuroleptic treatment is established.

Clozapine's use is therefore reserved for people who have not responded to two other antipsychotics and is only done with stringent blood monitoring.

Clozapine became widely available in the early 1990s and remains the only treatment likely to be effective in treating resistant schizophrenia.

Clozapine is not normally associated with tardive dyskinesia and is recommended as the drug of choice when this is present, although some case reports describe clozapine-induced TD.

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Clozapine is on the World Health Organization's List of Essential Medicines.

Clozapine was synthesized in 1958 by Wander AG, a Swiss pharmaceutical company, based on the chemical structure of the tricyclic antidepressant imipramine.

Clozapine is a dibenzodiazepine that is structurally very similar to loxapine .

Clozapine is usually used for people diagnosed with schizophrenia who have had an inadequate response to other antipsychotics or who have been unable to tolerate other drugs due to extrapyramidal side effects.

Clozapine treatment has been demonstrated to produced improved outcomes in multiple domains including; a reduced risk of hospitalisation, a reduced risk of drug discontinuation, a reduction in overall symptoms and has improved efficacy in the treatment of positive psychotic symptoms of schizophrenia.

Clozapine is widely used in secure and forensic mental health settings where improvements in aggression, shortened admission and reductions in restrictive practice such as seclusion have been found.

Clozapine is used in emotionally unstable personality disorder and a randomised controlled trial is currently underway.

Clozapine is widely recognised as being underused with wide variation in prescribing, especially in patients with African heritage.

Clozapine "rechallenge" is when someone that experienced agranulocytosis while taking clozapine starts taking the medication again.

Clozapine-induced gastrointestinal hypomotility currently has a higher mortality rate than the better known side effect of agranulocytosis.

Clozapine-induced hypersalivation is likely a dose-related phenomenon, and tends to be worse when first starting the medication.

Clozapine is classified as an atypical antipsychotic drug because it binds to serotonin as well as dopamine receptors.

Clozapine is an antagonist at the 5-HT2A subunit of the serotonin receptor, putatively improving depression, anxiety, and the negative cognitive symptoms associated with schizophrenia.

Clozapine induces the release of glutamate and D-serine, an agonist at the glycine site of the NMDA receptor, from astrocytes, and reduces the expression of astrocytic glutamate transporters.

Clozapine prevents impaired NMDA receptor expression caused by NMDA receptor antagonists.

Clozapine is extensively metabolized in the liver, via the cytochrome P450 system, to polar metabolites suitable for elimination in the urine and feces.