|Brand names||Clozaril, Denzapine, FazaClo, Versacloz, Zaponex|
Clozapine is an atypical antipsychotic that was first synthesized in 1958. At the time all antipsychotics that had been synthesized were associated with dose-dependent movement disorders that were inseparable from their antipsychotic activity as both actions were mediated via antagonism (blocking) of the dopamine D2 receptors present in the brain. Hence it took some time before clozapine's antipsychotic effects became widely accepted.
In the early 1970s it was introduced into a few European countries such as Finland as a low-EPS yet very sedating antipsychotic. However, after it caused a few deaths via agranulocytosis[note 1] it was withdrawn from the worldwide market a mere two years after its introduction. It was later re-introduced in the early 1990s after several pivotal clinical trials in the 1980s proved beyond a reasonable doubt that it was uniquely effective in treatment-resistant cases of schizophrenia. It is also uniquely effective in reducing suicide rates in schizophrenics. In a recent Finnish study it was found that clozapine was associated with the lowest all-cause mortality (that is, death from any cause) amongst antipsychotics and that no antipsychotic treatment was associated with the highest mortality of all.
Its principal side effects (with their frequency in brackets) include: sedation (40%), weight gain (average is 1.7 kg/month), blood sugar abnormalities (potentially including type II diabetes mellitus), drooling, constipation (potentially to the point of ileus[note 2]), heart disorders,[note 3] unexplained fever (~5%), seizures, agranulocytosis (1-2%), hepatitis, vomiting, bed wetting, urinary incontinence, etc.
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- ↑ A severely compromised immune system; so compromised that a cold/flu can be fatal
- ↑ A paralysed bowel, can be fatal
- ↑ Including high heart rate and myocarditis, which is a heart infection that can be fatal
- ↑ Meltzer, HY; Alphs, L; Green, AI; Altamura, AC; Anand, R; Bertoldi, A; Bourgeois, M; Chouinard, G; Islam, MZ; Kane, J; Krishnan, R; Lindenmayer, JP; Potkin, S; International Suicide Prevention Trial Study Group (January 2003). "Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT).". Archives of General Psychiatry 60 (1): 82–91. PMID 12511175. doi:10.1001/archpsyc.60.1.82.
- ↑ Tiihonen, J; Lönnqvist, J; Wahlbeck, K; Klaukka, T; Niskanen, L; Tanskanen, A; Haukka, J (August 2009). "11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study).". Lancet 374 (9690): 620–7. PMID 19595447. doi:10.1016/S0140-6736(09)60742-X.
- ↑ Wetterling, T (January 2001). "Bodyweight gain with atypical antipsychotics. A comparative review.". Drug Safety 24 (1): 59–73. PMID 11219487. doi:10.2165/00002018-200124010-00005.
- ↑ Rossi, S, ed. (July 2014). "Clozapine". Australian Medicines Handbook. Adelaide, Australia: Australian Medicines Handbook Pty Ltd. Retrieved 17 August 2014.