Clotiapine

{{Short description|Antipsychotic medication}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 460045350

| IUPAC_name = 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzothiazepine

| image = Clotiapine.svg

| image_class = skin-invert-image

| width = 180

| image2 = File:Clotiapine ball-and-stick model.png

| tradename = Etumina, Etumine, Entumin, Etomine, Entumine

| Drugs.com = {{drugs.com|international|clotiapine}}

| pregnancy_category =

| legal_AU =

| legal_BR = C1

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}

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| legal_DE =

| legal_NZ =

| legal_UK =

| legal_US =

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| legal_status = Rx-only

| routes_of_administration = Oral, Intravenous and Intramuscular

| bioavailability =

| protein_bound =

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| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 2058-52-8

| ATC_prefix = N05

| ATC_suffix = AH06

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 304902

| PubChem = 16351

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 15510

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = Z05HCY0X1T

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D01597

| ChEBI = 108591

| C=18 | H=18 | Cl=1 | N=3 | S=1

| smiles = Clc2ccc1Sc4c(/N=C(\c1c2)N3CCN(C)CC3)cccc4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C18H18ClN3S/c1-21-8-10-22(11-9-21)18-14-12-13(19)6-7-16(14)23-17-5-3-2-4-15(17)20-18/h2-7,12H,8-11H2,1H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = KAAZGXDPUNNEFN-UHFFFAOYSA-N

}}

Clotiapine (Entumine) is an atypical antipsychotic{{cite journal | vauthors = Seminara G, Trassari V, Prestifilippo N, Chiavetta R, Calandra C | title = [Atypical tricyclic neuroleptics for treatment of schizophrenia. Clothiapine and clozapine] | journal = Minerva Psichiatrica | volume = 34 | issue = 2 | pages = 95–99 | date = June 1993 | pmid = 8105359 }} of the dibenzothiazepine chemical class.{{Cite journal | vauthors = Schmutz J, Künzle F, Hunziker F, Gauch R | title = Über in 11-Stellung amino-substituierte Dibenzo[b,f]-1, 4-thiazepine und -oxazepine. 9. Mitteilung über siebengliedrige Heterocyclen | doi = 10.1002/hlca.19670500131 | journal = Helvetica Chimica Acta | volume = 50 | pages = 245–254 | year = 1967 }} It was first introduced in a few European countries (namely, Belgium, Italy, Spain and Switzerland), Argentina, Taiwan and Israel in 1970.

Some sources regard clotiapine as a typical antipsychotic rather than atypical due to its high incidence of extrapyramidal side effects compared to the atypicals like clozapine and quetiapine, to which it is structurally related.{{cite journal | vauthors = Geller V, Gorzaltsan I, Shleifer T, Belmaker RH, Bersudsky Y | title = Clotiapine compared with chlorpromazine in chronic schizophrenia | journal = Schizophrenia Research | volume = 80 | issue = 2–3 | pages = 343–347 | date = December 2005 | pmid = 16126373 | doi = 10.1016/j.schres.2005.07.007 | s2cid = 22340010 }} Despite the relativity high rate of undesired effects it has demonstrated efficacy in treatment-resistant individuals with schizophrenia according to a number of psychiatrists with clinical experience with it, some weak clinical evidence supports this view too.{{cite journal|title=Clotiapine: Another forgotten treasure in psychiatry?|journal=European Neuropsychopharmacology|volume=7|issue=Suppl 2|pages=S217|doi=10.1016/S0924-977X(97)88712-3|date=September 1997| vauthors = Lokshin P, Kotler M, Belmaker RH |s2cid=54246576 }}{{cite journal | vauthors = Van Wyk AJ, Marais GF | title = Chlorpromazine, clotiapine and thioridazine--a comparative clinical trial on Bantu psychotic patients | journal = South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde | volume = 45 | issue = 34 | pages = 945–947 | date = August 1971 | pmid = 4939661 | url = http://archive.samj.org.za/1971%20VOL%20XLV%20Jul-Dec/Articles/08%20August/4.3%20CHLORPROMOZAINE,%20CLOTIAPINE%20AND%20THIORIDAZINE%20-%20A%20COMPARATIVE%20CLINICAL%20TRIAL%20AND%20BANTU%20PSYCHOT.pdf }} A systematic review performed by Cochrane compared clotiapine with other antipsychotic drugs:

class="wikitable" |+ Clotiapine compared to other antipsychotic drugs for acute psychotic illnesses{{cite journal | vauthors = Carpenter S, Berk M, Rathbone J | title = Clotiapine for acute psychotic illnesses | journal = The Cochrane Database of Systematic Reviews | volume = 2004 | issue = 4 | pages = CD002304 | date = October 2004 | pmid = 15495032 | pmc = 8985500 | doi = 10.1002/14651858.CD002304.pub2 }}
Summary
There was no evidence to support or refute the use of clotiapine in preference to other antipsychotic drug treatments for management of people with acute psychotic illness.
style="padding:0;" | {| class="wikitable collapsible collapsed" style="width:100%;"
scope="col" style="text-align: left;"| Outcome ! scope="col" style="text-align: left;"| Findings in words ! scope="col" style="text-align: left;"| Findings in numbers ! scope="col" style="text-align: left;"| Quality of evidence
colspan="4" style="text-align: left;"| General clinical impression
No significant improvement	There is no clear difference between people given clotiapine and those receiving other antipsychotic drugs for acute psychotic illnesses. These findings are based on data of low quality.	RR 0.88 (0.39 to 1.98)	Low
Not well enough to be discharged	Clotiapine is not clearly different to other antipsychotic drugs for this outcome - for people who are acutely unwell. These findings are based on data of low quality.	RR 1.04 (0.93 to 1.16)	Low
colspan="4" style="text-align: left;"| Adverse effects
Movement disorders - use of antiparkinsonian medication	Clotiapine may reduce the use of antiparkinsonian drugs - implying that clotiapine causes less of this effect, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited.	RR 0.43 (0.05 to 3.53)	Very low
Seizure	Clotiapine may increase the risk of fits, but, the difference between the two treatments is not clear. This finding is based on data of low quality.	RR 3.67 (0.16 to 84.66)	Low
colspan="4" style="text-align: left;"| Satisfaction with care
Leaving the study early - any reason	There is no clear difference between people given clotiapine and those receiving other antipsychotics for acute psychotic illnesses. These findings are based on data of low quality.	RR 2.09 (0.81 to 5.42)	Low
	No study reported any data on outcomes as sedation and information relating to behavioral outcomes such as tranquillisation.		Clotiapine increases very fast weight, like approximately in 6 or 7 days of the start, so it is convenient to speak with your doctor it this happens.

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A fatal case of urinary retention associated with this drug has been reported in literature.Mannocchi G, Pantano F, Tittarelli R, Catanese M, Umani Ronchi F, Busardò FP (2015) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=26236337 Development and Validation of a GC-MS Method for the Detection and Quantification of Clotiapine in Blood and Urine Specimens and Application to a Postmortem Case.] Int J Anal Chem 2015 ():972480. [http://dx.doi.org/10.1155/2015/972480 DOI:10.1155/2015/972480] PMID: [https://pubmed.gov/26236337 26236337]