| Revision as of 11:55, 5 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456798125 of page Perphenazine for the Chem/Drugbox validation project (updated: ''). |
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{{Short description|Antipsychotic medication}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{drugbox | Verifiedfields = changed |
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{{drugbox |
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| Watchedfields = changed |
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| verifiedrevid = 413953730 |
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| verifiedrevid = 464199413 |
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| IUPAC_name = 2-piperazin-1-yl]ethanol |
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| IUPAC_name = 2-piperazin-1-yl]ethanol |
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| image = Perphenazine.svg |
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| image = Perphenazine.svg |
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| width = 250 |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| pregnancy_AU = C |
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| pregnancy_AU = C |
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| pregnancy_US = C |
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| pregnancy_US = C |
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| legal_AU = |
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| legal_BR = C1 |
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| legal_BR_comment = <ref>{{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=] |language=pt-BR |publication-date=2023-04-04}}</ref> |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| routes_of_administration = oral and i.m. |
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| routes_of_administration = Oral and ] |
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| class = ] |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = 40% |
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| bioavailability = 40% |
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| metabolism = hepatic |
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| metabolism = hepatic |
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| elimination_half-life = 8-12 (up to 20) hours |
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| elimination_half-life = 8–12 (up to 20) hours |
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| excretion = biliar |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 58-39-9 |
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| CAS_number = 58-39-9 |
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| PubChem = 4748 |
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| PubChem = 4748 |
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| IUPHAR_ligand = 209 |
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| IUPHAR_ligand = 209 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00850 |
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| DrugBank = DB00850 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00503 |
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| KEGG = D00503 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 8028 |
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| ChEBI = 8028 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=21 | H=26 | Cl=1 | N=3 | O=1 | S=1 |
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| C=21 | H=26 | Cl=1 | N=3 | O=1 | S=1 |
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| molecular_weight = 403.97 |
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| smiles = Clc2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(CCO)CC4 |
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| smiles = Clc2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(CCO)CC4 |
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| InChI = 1/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2 |
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| StdInChI = 1S/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2 |
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| StdInChIKey = RGCVKNLCSQQDEP-UHFFFAOYSA-N |
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| StdInChIKey = RGCVKNLCSQQDEP-UHFFFAOYSA-N |
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}} |
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}} |
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'''Perphenazine''' is a ] ]. Chemically, it is classified as a piperazinyl ]. Originally marketed in the ] as '''Trilafon''', it has been in clinical use for decades. |
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Perphenazine is roughly ten times as potent as ] at the ];<ref>{{cite journal | vauthors = Rees L | title = Chlorpromazine and allied phenothiazine derivatives | journal = British Medical Journal | volume = 2 | issue = 5197 | pages = 522–5 | date = August 1960 | pmid = 14436902 | pmc = 2097091 | doi = 10.1136/bmj.2.5197.522 }}</ref> thus perphenazine is considered a medium-potency antipsychotic.<ref>{{cite journal | vauthors = Ascher-Svanum H, Zhu B, Faries D, Landbloom R, Swartz M, Swanson J | title = Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia | journal = BMC Psychiatry | volume = 6 | pages = 8 | date = February 2006 | pmid = 16504026 | pmc = 1402287 | doi = 10.1186/1471-244X-6-8 | doi-access = free }}</ref><ref name="Freu">{{cite book | vauthors = Freudenreich O | title=Psychotic disorders | url=https://books.google.com/books?id=Y58hbZN-lZYC | access-date=2009-06-22 | series=Practical Guides in Psychiatry | year=2007 | publisher=Lippincott Williams & Wilkins | isbn=978-0-7817-8543-3 | page=88 | chapter=Treatment of psychotic disorders | chapter-url=https://books.google.com/books?id=Y58hbZN-lZYC&pg=PA88 }}</ref> |
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==Medical uses== |
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In low doses it is used to treat ] (together with an ]). Fixed combinations of perphenazine and the ] ] in different proportions of weight exist (see Etrafon below). When treating depression, perphenazine is discontinued as fast as the clinical situation allows.{{Citation needed|date=June 2009}} Perphenazine has no intrinsic antidepressive activity. Several studies show that the use of perphenazine with ] (Prozac) in patients with psychotic depression is most promising, although fluoxetine interferes with the metabolism of perphenazine, causing higher plasma levels of perphenazine and a longer half-life. In this combination the strong ] action of perphenazine attenuates fluoxetine-induced ] and ] (emesis), as well as the initial agitation caused by fluoxetine. Both actions can be helpful for many patients. |
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Perphenazine has been used in low doses as a 'normal' or 'minor' tranquilizer in patients with a known history of addiction to drugs or ], a practice which is now strongly discouraged.{{Citation needed|date=October 2009}} |
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Perphenazine has sedating and ] properties, making the drug useful for the treatment of agitated psychotic patients. |
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A valuable off-label indication is the short-time treatment of ], in which pregnant women experience violent nausea and vomiting. This problem can become severe enough to endanger the pregnancy. As perphenazine has not been shown to be ] and works very well, it is sometimes given orally in the smallest possible dose. |
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===Effectiveness=== |
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Perphenazine is used to treat psychosis (e.g. in people with ] and the ] phases of ] and OCD). Perphenazine effectively treats the positive symptoms of schizophrenia, such as hallucinations and delusions, but its effectiveness in treating the negative symptoms of schizophrenia, such as ] and ], is unclear. Earlier studies found the typical antipsychotics to be ineffective or poorly effective in the treatment of negative symptoms,<ref name="King">{{cite journal | vauthors = King DJ | title = Drug treatment of the negative symptoms of schizophrenia | journal = European Neuropsychopharmacology | volume = 8 | issue = 1 | pages = 33–42 | date = February 1998 | pmid = 9452938 | doi = 10.1016/S0924-977X(97)00041-2 | s2cid = 37692796 }}</ref> but two recent, large-scale studies found no difference between perphenazine and the atypical antipsychotics.<ref name="Lieb">{{cite journal | vauthors = Lieberman JA | title = Comparative effectiveness of antipsychotic drugs. A commentary on: Cost Utility Of The Latest Antipsychotic Drugs In Schizophrenia Study (CUtLASS 1) and Clinical Antipsychotic Trials Of Intervention Effectiveness (CATIE) | journal = Archives of General Psychiatry | volume = 63 | issue = 10 | pages = 1069–72 | date = October 2006 | pmid = 17015808 | doi = 10.1001/archpsyc.63.10.1069 }}</ref> A 2015 ] compared perphenazine with other antipsychotic drugs: |
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{| class="wikitable" |
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|+ Perphenazine compared with any antipsychotic drug for schizophrenia<ref name=Har2015>{{cite journal | vauthors = Hartung B, Sampson S, Leucht S | title = Perphenazine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 3 | pages = CD003443 | date = March 2015 | pmid = 25749632 | pmc = 7173727 | doi = 10.1002/14651858.CD003443.pub3 }}</ref> |
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! Summary |
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|Although perphenazine has been used in ] for more than 50 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. All data for the main outcomes were of very low quality evidence. At best it can be said that perphenazine showed similar effects—including adverse events—as several of the other ] drugs.<ref name=Har2015/> |
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{| class="wikitable collapsible collapsed" style="width:100%;" |
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! scope="col" style="text-align: left;"| Outcome |
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! scope="col" style="text-align: left;"| Findings in words |
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! scope="col" style="text-align: left;"| Findings in numbers |
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! scope="col" style="text-align: left;"| Quality of evidence |
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! colspan="4" style="text-align: left;"| Global state |
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| No better or deterioration<br />Follow-up: mean 8 weeks || Perphenazine is not clearly different from other drugs for this global outcome and data supporting this finding are very limited. || ] 1.04 (0.91 to 1.17) || ] |
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! colspan="4" style="text-align: left;"| ] |
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| Mental state - 'no effect' (] score reduction)<br />Follow-up: average 8 weeks || At present it is not possible to be confident about the difference between perphenazine and any other antipsychotic drug. Data supporting this finding are very limited. || ] 1.24 (0.61 to 2.52) || ] |
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! colspan="4" style="text-align: left;"| ]s |
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| ] adverse effects - dystonia<br />Follow-up: average 10 weeks || Perphenazine is not clearly different to other antipsychotic drugs and data supporting this finding are very limited. || ] 1.36 (0.23 to 8.16) || ] |
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| Any serious adverse event<br />Follow-up: average 39 weeks || It is also not possible to be confident about the difference between the two treatments. Data supporting this finding are very limited. || ] 0.98 (0.68 to 1.41) || ] |
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| || No study reported any data on outcomes such as death, economic outcomes and information relating to time in services|| || |
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==Side effects== |
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As a member of the phenothiazine type of antipsychotics, perphenazine shares in general all allergic and toxic side-effects of ]. A 2015 systematic review of the data on perphenazine conducted by the ] concluded that "there were no convincing differences between perphenazine and other antipsychotics" in the incidence of adverse effects.<ref name=Har2015/> Perphenazine causes early and late ]s more often than ], and at a similar rate to other medium-potency antipsychotics<ref name="Kels">{{cite book | vauthors = Kelsey JE, Newport DJ, Nemeroff CB | title=Principles of psychopharmacology for mental health professionals | url=https://books.google.com/books?id=FxaBz-ufvN0C | access-date=2009-06-22 | edition=illustrated |
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| year=2006 | publisher=John Wiley and Sons | isbn=978-0-471-25401-0 | page=114 | chapter=Schizophrenia |
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| chapter-url=https://books.google.com/books?id=FxaBz-ufvN0C&pg=PA114 }}</ref> and the atypical antipsychotic ].<ref name="Schil">{{cite journal | vauthors = Schillevoort I, de Boer A, Herings RM, Roos RA, Jansen PA, Leufkens HG | title = Antipsychotic-induced extrapyramidal syndromes. Risperidone compared with low- and high-potency conventional antipsychotic drugs | journal = European Journal of Clinical Pharmacology | volume = 57 | issue = 4 | pages = 327–31 | date = July 2001 | pmid = 11549212 | doi = 10.1007/s002280100302 | hdl = 1874/27881 | s2cid = 11934011 | hdl-access = free }}</ref><ref name="Risp">{{cite journal | vauthors = Høyberg OJ, Fensbo C, Remvig J, Lingjaerde O, Sloth-Nielsen M, Salvesen I | title = Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations | journal = Acta Psychiatrica Scandinavica | volume = 88 | issue = 6 | pages = 395–402 | date = December 1993 | pmid = 7508675 | doi = 10.1016/S0149-2918(98)80046-5 }}</ref> |
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When used for its strong ] or ] effects in cases with associated brain injuries, it may obscure the clinical course and interferes with the diagnosis. High doses of perphenazine can cause temporary dyskinesia. As with other typical antipsychotics, permanent or lasting ] is a risk. |
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===Discontinuation=== |
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The ] recommends a gradual withdrawal when ] to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book |editor1-first=BMJ | editor = Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book | vauthors = Haddad P, Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=9780198527480 |page=207-216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |language=en}}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/> |
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There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in reoccurrence of the condition that is being treated.<ref>{{cite book | vauthors = Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=9788847026797 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |language=en}}</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/> |
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==Pharmacology== |
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===Pharmacodynamics=== |
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Perphenazine has the following binding profile towards cloned human receptors unless otherwise specified:<ref>National Institute of Mental Health. PDSD Ki Database (Internet) . Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: {{cite web |url=http://pdsp.med.unc.edu/pdsp.php |title=PDSP Database - UNC |access-date=2013-11-03 |url-status=dead |archive-url=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archive-date=2013-11-08 }}</ref><ref>{{cite journal | vauthors = Sweet RA, Pollock BG, Mulsant BH, Rosen J, Sorisio D, Kirshner M, Henteleff R, DeMichele MA | display-authors = 6 | title = Pharmacologic profile of perphenazine's metabolites | journal = Journal of Clinical Psychopharmacology | volume = 20 | issue = 2 | pages = 181–7 | date = April 2000 | pmid = 10770456 | doi = 10.1097/00004714-200004000-00010 }}</ref> |
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{| class="wikitable sortable" |
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! Molecular target !! Binding affinity (K<sub>i</sub>) for perphenazine !! Binding affinity (K<sub>i</sub>) for dealkylperphenazine !! Binding affinity (K<sub>i</sub>) for 7-hydroxyperphenazine |
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| ] || 421 || - || - |
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| ] || 5.6 || 54 || 38 |
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| ] || 132 || - || - |
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| ] || 17 || - || - |
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| ] || 23 || - || - |
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| ] || 10 || - || - |
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| ] || 810 || - || - |
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| ] || 104.9 || - || - |
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| ] || 85.2 || - || - |
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| ] || 2000 || 130 || 3400 |
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| ] || 1848 || - || - |
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| ] || 29.9 (RS) || - || - |
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| ] || 0.765 || - || - |
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| D<sub>2L</sub> receptor || 3.4 || 85 || 4.1 |
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| ] || 0.13 || - || - |
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| ] || 17 || - || - |
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| D<sub>4.4</sub> receptor || 140 || 690 || 620 |
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| ] || 8 || - || - |
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| ] || 18.5 (RB) || - || - |
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<br /> |
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'''Acronyms:'''<br /> |
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RS — Rat striatum receptor.<br /> |
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RB — Rat brain receptor. |
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===Pharmacokinetics=== |
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Perphenazine has an oral ] of approximately 40% and a half-life of 8 to 12 hours (up to 20 hours), and is usually given in 2 or 3 divided doses each day. It is possible to give two-thirds of the daily dose at bedtime and one-third during breakfast to maximize hypnotic activity during the night and to minimize daytime ] and ] without loss of therapeutic activity. |
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{{Pharmacokinetics of long-acting injectable antipsychotics}} |
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==Formulations== |
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It is sold under the brand names Trilafon (single drug) and Etrafon/Triavil/Triptafen<ref>{{Cite web|url=http://www.mind.org.uk/information-support/drugs-and-treatments/antidepressants-a-z/triptafen/|title=Triptafen {{!}} Mind, the mental health charity - help for mental health problems|website=www.mind.org.uk|language=en|access-date=2017-03-19}}</ref> (contains fixed dosages of amitriptyline). A brand name in Europe is Decentan pointing to the fact that perphenazine is approximately 10-times more potent than chlorpromazine. Usual oral forms are tablets (2, 4, 8, 16 mg) and liquid concentrate (4 mg/ml). |
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The 'Perphenazine injectable USP' solution is intended for deep ] (i.m.) injection, for patients who are not willing to take oral medication or if the patient is unable to swallow. Due to a better bioavailability of the injection, two-thirds of the original oral dose is sufficient. The incidence of hypotension, sedation and extrapyramidal side-effects may be higher compared to oral treatment. The i.m.-injections are appropriate for a few days, but oral treatment should start as soon as possible. |
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In many countries, depot forms of perphenazine exist (as ] and ]). One injection works for 1 to 4 weeks depending on the dose of the depot-injection. Depot-forms of perphenazine should not be used during the initial phase of treatment as the rare ] may become more severe and uncontrollable with this form. Extrapyramidal side-effects may be somewhat reduced due to constant plasma-levels during depot-therapy. Also, patient compliance is sure, as many patients do not take their oral medication, particularly if feeling better once improvement in psychosis is achieved. |
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==Interactions== |
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Fluoxetine causes higher plasma levels and a longer ] of perphenazine, therefore a dose reduction of perphenazine might be necessary. |
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Perphenazine intensifies the central depressive action of drugs with such activity (tranquilizers, hypnotics, narcotics, ], ]-]s etc.). A dose reduction of perphenazine or the other drug may be necessary. |
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In general, all ]s may lead to seizures in combination with the opioid ] (Ultram). |
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Perphenazine may increase the ] needs of ] patients. Monitor ]s of insulin-dependent patients regularly during long-term treatment. |
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==References== |
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{{Reflist}} |
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{{Antipsychotics}} |
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{{Tricyclics}} |
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