Talk:Clozapine

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[edit] "Awakenings" and Tardive dyskinesia

Why no mention of "awakenings" - when patients take the drug for a prolonged period and then suddenly wake up, no voices, no fog? See this: http://www.time.com/time/magazine/article/0,9171,975910-2,00.html

Being a dopamine-antagonist, shouldn't we mention Tardive dyskinesia as a risk? —Preceding unsigned comment added by 71.249.64.128 (talk) 04:44, 8 December 2007 (UTC)

Regarding TD, guess what's so special about clozapine as an antipsychotic? Hum? Yes, got it! It doesn't cause TDs. There are some case descriptions, but to my knowledge, no grave, irreversible tardive dyskinesiae were accounted to clozapine alone (some occured in patients treated by typical or other APs prior to or after clozapine); in fact, clozapine is commonly used to (co)treat tardive dyskinesiae.--84.163.111.84 (talk) 20:39, 17 May 2008 (UTC)

[edit] No critical analysis of Clozapine

In order to have a balanced article, critics' views of the drug are needed. This would provide more information regardless of personal view. —The preceding unsigned comment was added by 66.108.112.105 (talk) 04:02, 24 April 2007 (UTC).

[edit] Clozapine for insomnia

The article mentions off label use of clozapine for treating refractory insomnia. However, this seems a bit extreme given its risk of agranulocytosis as well as how closely this medication is regulated. In addition, there are multiple alternatives (benzodiazepenes, etc.) to clozapine for treating insomnia. Is anyone familiar with this type of use? Andrew73 14:16, 27 October 2005 (UTC)

I found this indication in the standard literature Benkert/Hippius (Springer Verlag). It should be noted that Clozapine is to be considered only for the treatment of severe insomnia that proved resistant to all other means of treatment (including benzodiazepines, cyclopyrones, L-Tryptophan, antidepressants, other antipsychotics, and psychotherapy). Clozapine is not in all countries subject to restriction. Klaus, 13 November 2005, 12:07

[edit] Technical description

I saw Clozapine referred to as "a tetracyclic dibenzodiazepine antipsychotic agent"; if I knew that that meant I'd try to add it to the article somehow. 128.113.144.115 00:30, 30 September 2006 (UTC)

Clozapine is exactly as not a tetracyclic as haloperidol is not a tricyclic. In order to define "polycyclicity", you have to count the (hetero)cycles, that are condensed; by this definition, clozapine is an (atypical) tricyclic antipsychotic, because it is a derivative of dibenzodiazepine, which in turn is a tricyclic structure.--Spiperon 15:57, 1 May 2007 (UTC)

[edit] Clozapine action on D1 dopamine receptor

Quote from the article Equivalent Occupancy of Dopamine D1 and D2 Receptors With Clozapine: Differentiation From Other Atypical Antipsychotics: "On the other hand, there is some evidence that clozapine behaves as a D1 agonist: hypothermia produced by clozapine in rats was fully antagonized by either of the selective D1 receptor antagonists SCH23390 or NNC 01–687 (41). This aspect could be interesting given the clinical and laboratory observations implicating D1 receptor agonism in the prefrontal cortex in cognitive functions (41, 42). Finally, regardless of its agonist/antagonist action, a recent [18F]fluorodeoxyglucose PET study in patients suffering from treatment-resistant schizophrenia showed that brain metabolic and clinical responses to clozapine were related to D1 receptor genotype (43). After 5 weeks of treatment with clozapine, brain metabolic decreases were found in patients with the 2,2 but not the 1,2 D1 receptor genotype. Moreover, patients with the 2,2 D1 genotype significantly improved with clozapine, whereas those with a 1,2 D1 genotype did not (43)."

This differential reaction of people with different types of D1 seemed interesting to me. --CopperKettle 13:03, 27 November 2006 (UTC)

[edit] First paragraph

I think it's misleading to say that it "was the first of the atypical antipsychotics to be developed" and then say "It was approved by the United States Food and Drug Administration (FDA) in 1989", as if it wasn't discovered/marketed until the 1980s. I think there should be some mention of its previous use, withdrawal, and reintroduction in the opening paragraph. --Galaxiaad 09:54, 16 February 2007 (UTC)

[edit] Genetic test to predict the risk of agranulocytosis

I think the information on the link between HLA DQB1 gene and agranulocytosis and some info about the recently introduced test could be added to the article.

The PGxPredict:CLOZAPINE test makes it possible to provide patients with specific information about their probability of developing agranulocytosis in response to clozapine.

--CopperKettle 11:43, 16 February 2007 (UTC)

Added the information; gave two references - to the company site and to the Forbes press-release; Found only one (PMID 11281944) PubMed paper linking HLA-DQB1 to the agranulocytosis risk, but abstained from adding it, cause this particular paper may be not related. --CopperKettle 02:58, 9 March 2007 (UTC) I've placed it into "Side effects" section, but it could be moved into "Monitoring"; I chose not to cause the test is not widely used as of now. --CopperKettle 09:41, 9 March 2007 (UTC)

[edit] Edited for junk

Removed the line "Treatment of But Rape" from the list of possible additional uses. Clearly junk.

24.113.82.222 01:34, 9 March 2007 (UTC)

[edit] Clozapine developement

Clozapine was not developed by Sandoz. In fact, it was created first in the late 1950s in laboratories of Wander AG, which was merged with Sandoz in 1967. The brand-mark Leponex (Europe) and Clozaril (US) were brought by the Sandoz in 1969-1971, I think.--84.163.106.158 20:59, 12 May 2007 (UTC)

Further, clozapine was not withdrawn in all lands after the drug-related death cases due to agranulocytosis in the early 1970s; in most countries, yes, but e.g. in Germany, it was soon re-introduced and in Czechoslovakia it wasn't withdrawn at all, the prescription was only restricted and strict therapeutic monitoring was made compulsory.--84.163.123.104 10:41, 13 May 2007 (UTC)

[edit] Dosage information

Would anyone object to removal of the dosage section? It is currently completely unreferenced and very prescriptive. Also, WP:MEDMOS specifically discourages the addition of such information to articles, as it is easily subject to vandalism and uninformed good-faith edits. Fvasconcellos (t·c) 02:09, 18 June 2007 (UTC)

Umm..normally yes but clozapine is a special case as it has a very strict commencement criteria as written here. I will try to get a ref. Another approach maybe to write "Due to risk of serious side effects, clozapine is commenced at a very low dose (25mg daily) and increased slowly until a therapeutic dose of 300-600 mg daily is reached" cheers, Casliber (talk · contribs) 13:34, 21 June 2007 (UTC)
That's perfectly fine by me, I've reworded accordingly and hopefully not detracted from the clarity of your draft. I'd still like this article to be very closely watched to prevent these figures being vandalized, though—would you like to help me on this one? :) Fvasconcellos (t·c) 00:01, 22 June 2007 (UTC)
P.S.: Text as it was for easy reference:
Start with 12.5 mg bedtime dose (6.25 mg in outpatients). The dose might then by increased cautiously by 25mg daily. The usual effective dose is 150 mg to 600 mg. In severely ill and/or younger patients up to 900 mg may be needed. In the elderly much lower doses may be sufficient (25 to 100 mg). The greater part or all of the daily dose may be given at bedtime, once maintenance dose has been determined, in order to minimize daytime sedation and orthostatic problems.
Yep added a bit -bd dosing sucks for long term compliance. All antispychotic effects are long term so bd dosing generally makes no sense once a person is stabilised. cheers, Casliber (talk · contribs) 02:18, 22 June 2007 (UTC)


Is it possible to give a reference and provide more details on the following: "In the elderly, much lower doses may be sufficient (25 to 100 mg)". My wife is only 38, she has been on 100 mg for 4 years. Currently she is on 75 mg and Clozaril still works for her. I am interested in studies on even lower dosage.

[edit] Citing the article

I didn't really wanna mess up the whole article with a bunch of cite needed tags, but I'll work on them this week -much easier to get refs at work. cheers, Casliber (talk · contribs) 14:51, 24 June 2007 (UTC)

Good luck :) The article's coming along very well. BTW, if you'd like to add to the history section, PMID 17580753 seems very interesting (I don't have access, though, so I can't speak to its accuracy). Fvasconcellos (t·c) 15:00, 24 June 2007 (UTC)
Thanks for the tip - will check that one at work.cheers, Casliber (talk · contribs) 15:09, 24 June 2007 (UTC)
One more article which may be interesting: PMID 11900316, free on Medscape. Fvasconcellos (t·c) 14:37, 2 July 2007 (UTC)

[edit] Some thoughts

For your consideration :)

  • Might it be a good idea to separate agranulocytosis and cardiac side effects as subheadings of Adverse effects? That could help to keep things organized, e.g. keep the pharmacogenetic test bit together with the introduction on agranulocytosis, and perhaps expand a bit on cardiomyopathy/myocarditis?
agree. These are the two biggies.
  • Goodman & Gilman's mentions ileus as a particular concern of clozapine use—worth mentioning?
? - never heard of or seen that one...maybe mention as a one off if at all.
  • Mention possibility of relapse with abrupt withdrawal? (Unnecessary?)
Sort of unnecessary-self explanatory I'd have thought.
  • I can't find a specific source for the sexual dysfunction paragraph with regard to clozapine in particular. Should it be commented out?
It is known and there should be a ref for it somewhere...
  • As for cites, this nice article from MedSafe (NZ pharm regulatory authority) may provide some sources, at least for the Adverse effects section.
Brilliant. Was nosing round work and there were bugger all refs in all the cloazpine blurbs. Not gone online yet.

Best, Fvasconcellos (t·c) 02:21, 26 June 2007 (UTC)

Ditto cheers, Casliber (talk · contribs) 06:18, 26 June 2007 (UTC)
Argh Current Opinion - totally forgot about that mag -always a goodie for thistype of thing....cheers, Casliber (talk · contribs) 19:59, 2 July 2007 (UTC)

[edit] Access to Full CBC

Methinks this is not correct. The only two things that are measured and entered in the subject registry are WBC and ANC. (And ANC, if not measured, can be calculated from WBC and other data.) Source: firsthand experience. elpincha 12:50, 12 November 2007 (UTC)

What is ANC? neutrophil count? You are correct in that only white cells and neutrophils need be measured, for practical purposes this means a full blood count. Cheers, Casliber (talk · contribs) 21:47, 17 May 2008 (UTC)