Clotiapine

Clotiapine (Entumine) is an atypical antipsychotic[1] of the dibenzothiazepine chemical class.[2] It was first introduced in a few European countries (namely, Belgium, Italy, Spain and Switzerland), Argentina, Taiwan and Israel in 1970.[3]

Clotiapine

Clinical data
Trade names	Etumina, Etumine, Entumin, Etomine, Entumine
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral, Intravenous and Intramuscular
ATC code	N05AH06 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzothiazepine
CAS Number	2058-52-8^N
PubChem CID	16351
ChemSpider	15510^Y
UNII	Z05HCY0X1T
KEGG	D01597^Y
ChEMBL	ChEMBL304902^Y
CompTox Dashboard (EPA)	DTXSID5022851
ECHA InfoCard	100.016.512
Chemical and physical data
Formula	C18H18ClN3S
Molar mass	343.87 g·mol^−1
3D model (JSmol)	Interactive image
SMILES Clc2ccc1Sc4c(/N=C(\c1c2)N3CCN(C)CC3)cccc4
InChI InChI=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^Y Key:KAAZGXDPUNNEFN-UHFFFAOYSA-N^Y
^NY (what is this?)  (verify)

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.[4] Despite its profile of a relatively high incidence of extrapyramidal side 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.[3][4][5] A systematic review compared clotiapine with other antipsychotic drugs:

Clotiapine compared to other antipsychotic drugs for acute psychotic illnesses[6]

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.[6]
Outcome Findings in words Findings in numbers Quality of evidence 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 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 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.

References

1. Seminara G, Trassari V, Prestifilippo N, Chiavetta R, Calandra C (June 1993). "[Atypical tricyclic neuroleptics for treatment of schizophrenia. Clothiapine and clozapine]". Minerva Psichiatrica. 34 (2): 95–9. PMID 8105359.
2. Schmutz J, Künzle F, Hunziker F, Gauch R (1967). "Über in 11-Stellung amino-substituierte Dibenzo[b,f]-1, 4-thiazepine und -oxazepine. 9. Mitteilung über siebengliedrige Heterocyclen". Helvetica Chimica Acta. 50: 245–254. doi:10.1002/hlca.19670500131.
3. Lokshin, P; Kotler, M; Belmaker, RH (September 1997). "Clotiapine: Another forgotten treasure in psychiatry?". European Neuropsychopharmacology. 7 (Suppl 2): S217. doi:10.1016/S0924-977X(97)88712-3.
4. Geller V, Gorzaltsan I, Shleifer T, Belmaker RH, Bersudsky Y (December 2005). "Clotiapine compared with chlorpromazine in chronic schizophrenia". Schizophrenia Research. 80 (2–3): 343–7. doi:10.1016/j.schres.2005.07.007. PMID 16126373.
5. Van Wyk AJ, Marais GF (August 1971). "Chlorpromazine, clotiapine and thioridazine--a comparative clinical trial on Bantu psychotic patients" (PDF). South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 45 (34): 945–7. PMID 4939661.
6. Carpenter S, Berk M, Rathbone J (October 2004). "Clotiapine for acute psychotic illnesses". The Cochrane Database of Systematic Reviews. 4 (4): CD002304. doi:10.1002/14651858.CD002304.pub2. PMID 15495032.