View source for Perphenazine

{{drugbox | verifiedrevid = 266114731
|
| IUPAC_name = 2-[4-[3-(2-chloro-10H-phenothiazin-10-yl) propyl]piperazin-1-yl]ethanol
| image = Perphenazine.svg
| CAS_number = 58-39-9
|  CASNo_Ref = {{cascite}}
| ATC_prefix = N05
| ATC_suffix = AB03
| PubChem = 4748
| IUPHAR_ligand = 209
| DrugBank = APRD00429
| C=21 | H=26 | Cl=1 | N=3 | O=1 | S=1
| molecular_weight = 403.97
| bioavailability = 40%
| metabolism = hepatic
| elimination_half-life = 8-12 (up to 20) hours
| excretion = biliar
| pregnancy_AU = C
| pregnancy_US = C
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = oral and i.m.
}}

'''Perphenazine''' is a [[typical antipsychotic]] [[psychoactive drug|drug]].  Chemically, it is classified as a piperazinyl [[phenothiazine]]. It has been in clinical use for decades.

Perphenazine is roughly five times as potent as [[chlorpromazine]];<ref>{{cite journal
| author = Rees L
| title = Chlorpromazine and allied phenothiazine derivatives
| journal = British Medical Journal
| volume = 2
| issue = 5197
| pages = 522–5
| year = 1960
| month = August
| pmid = 14436902
| pmc = 2097091
| doi = 10.1136/bmj.2.5197.522
| accessdate = 2009-06-22
}}</ref> thus perphenazine is considered a medium-potency antipsychotic.<ref>{{cite journal
| author = 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
| issue = 
| pages = 8
| year = 2006
| pmid = 16504026
| pmc = 1402287
| doi = 10.1186/1471-244X-6-8
| accessdate = 2009-06-22
}}</ref><ref name="Freu">{{cite book
|last=Freudenreich
|first=Oliver
|title=Psychotic disorders
|url=http://books.google.com/?id=Y58hbZN-lZYC
|accessdate=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
|chapterurl=http://books.google.co.uk/books?id=Y58hbZN-lZYC&pg=PA88&lpg=PA88&dq=perphenazine+eps+medium+potency&source=bl&ots=XCuOf1Zymn&sig=bZt_mF9cTFQn3U5-li2mCKloiOY&hl=en&ei=YN4_SrapC4S5jAer0rwH&sa=X&oi=book_result&ct=result&resnum=4
}}</ref> 

==Pharmacokinetics==
It has an oral bioavailability 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 [[sedation]] and [[hypotension]] without loss of therapeutic activity.

==Uses==
Perphenazine is used to treat psychosis (e.g. in [[schizophrenic]]s) and the [[manic]] phases of [[bipolar disorder]]. 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 [[flattened affect]] and [[poverty of speech]], 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
| author = King DJ
| title = Drug treatment of the negative symptoms of schizophrenia
| journal = European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
| volume = 8
| issue = 1
| pages = 33–42
| year = 1998
| month = February
| pmid = 9452938
| doi = 10.1016/S0924-977X(97)00041-2 
| accessdate = 2009-06-22
}}</ref> but two recent, large-scale studies found no difference between perphenazine and the atypical antipsychotics.<ref name="Lieb">{{cite journal
| author = 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
| year = 2006
| month = October
| pmid = 17015808
| doi = 10.1001/archpsyc.63.10.1069
| accessdate = 2009-06-22
}}</ref>

In low doses it is used to treat [[clinical depression|agitated depression]] (together with an [[antidepressant]]). Fixed combinations of perphenazine and the [[tricyclic antidepressant]] [[amitriptyline]] 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 [[fluoxetine]] (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 [[antiemetic]] action of perphenazine attenuates fluoxetine-induced [[nausea]] and [[vomiting]] (emesis), as well as the initial agitation caused by fluoxetine. Both actions can be helpful for many patients. 

Perphenazine has been used in low doses as a 'normal' or 'minor' tranquilizer in patients with a known history of addiction to drugs or alcohol, a practice which is now strongly discouraged.<ref> [http://www.mentalhealth.com/drug/p30-t05.html#Head_4 "Perphenazine, Warnings mentalhealth.com"], Retrieved 2010-1-24. </ref> {{Citation needed|date=October 2009}}

Perphenazine has sedating and [[anxiolytic]] properties, making the drug useful for the treatment of agitated psychotic patients and, in high doses (up to 100&nbsp;mg per day), for patients with life-threatening (febrile) [[catatonia]], a state in which the patients are extremely agitated, but unable to express themselves. In this situation perphenazine may be used together with [[electroconvulsive therapy]] and correction of [[electrolyte]]s and fluids in the body.

A valuable off-label indication is the short-time treatment of [[hyperemesis gravidarum]], in which pregnant women experience violent nausea and vomiting. This problem can become severe enough to endanger the life of the unborn. As perphenazine has not been shown to be [[teratogenic]] and works very well, it is sometimes given orally in the smallest possible dose.

==Side effects==
As a member of the phenothiazine type of antipsychotics, perphenazine shares in general all allergic and toxic side-effects of [[chlorpromazine]].  A 2005 [[systematic review]] of the data on perphenazine conducted by the [[Cochrane Collaboration]] concluded that "there were no convincing differences between perphenazine and other antipsychotics" in the incidence of adverse effects.<ref name="Hart">{{cite journal
| author = Hartung B, Wada M, Laux G, Leucht S
| title = Perphenazine for schizophrenia
| journal = Cochrane Database of Systematic Reviews (Online)
| issue = 1
| pages = CD003443
| year = 2005
| pmid = 15674907
| doi = 10.1002/14651858.CD003443.pub2
| accessdate = 2009-06-22
}}</ref> Perphenazine causes early and late [[extrapyramidal side effect]]s more often than [[placebo]], and at a similar rate to other medium-potency antipsychotics<ref name="Kels">{{cite book
|last1=Kelsey
|first1=Jeffrey E
|last2=Newport
|first2=D Jeffrey
|last3=Nemeroff
|first3=Charles B
|title=Principles of psychopharmacology for mental health professionals
|url=http://books.google.com/?id=FxaBz-ufvN0C
|accessdate=2009-06-22
|edition=illustrated
|year=2006
|publisher=John Wiley and Sons
|isbn=978-0-471-25401-0
|page=114
|chapter=Schizophrenia
|chapterurl=http://books.google.co.uk/books?id=FxaBz-ufvN0C&pg=PA114&lpg=PA114&dq=perphenazine+as+other+medium-potency+antipsychotics&source=bl&ots=fUBfxM2H-y&sig=AFb4g4aMDxS0OF028f-Oe8WT82s&hl=en&ei=2t4_SqPDC93LjAfSzakV&sa=X&oi=book_result&ct=result&resnum=2
}}</ref> and the atypical antipsychotic [[risperidone]].<ref name="Schil">{{cite journal
| author = 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
| year = 2001
| month = July
| pmid = 11549212
| doi = 10.1007/s002280100302
| accessdate = 2009-06-22
}}</ref><ref name="Risp">{{cite journal
| author = 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
| year = 1993
| month = December
| pmid = 7508675
| doi = 10.1016/S0149-2918(98)80046-5 
| accessdate = 2009-06-22
}}</ref>

When used for its strong [[antiemetic]] or [[antivertignosic]] 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 [[tardive dyskinesia]] is a risk.

==Formulations==
It is sold under the brand names Trilafon (single drug) and Etrafon/Triavail (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&nbsp;mg) and liquid concentrate (4&nbsp;mg/ml).

The 'Perphenazine injectable USP' solution is intended for deep [[intramuscular]] (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.    

In many countries, depot forms of perphenazine exist (as perphenazine [[enanthate]]). 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 [[neuroleptic malignant syndrome]] 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 mediaction, particularly if feeling better once improvement in psychosis is achieved.

==Interactions==
Fluoxetine causes higher plasma-levels and a longer half-life of perphenazine, therefore a dose reduction of perphenazine might be necessary.

Perphenazine intensifies the central depressive action of drugs with such activity (tranquilizers, hypnotics, narcotics, antihistaminics, OTC-antiemetics etc.). A dose reduction of perphenazine or the other drug may be necessary.

The [[antihelmintic]] drug piperazine may intensify extrapyramidal side-effects. Avoid the concomitant use. Also, neurotoxic side-effects of the antibiotic streptomycin as well as of other aminoglycosids on the VIII. Brain nerve my be masked due to the strong antivertignosic effect of perphenazine. Avoid the concomitant use, too.

In general, all [[neuroleptic]]s may lead to seizures in combination with the opioid tramadol (Ultram).

Perphenazine may increase the [[insulin]] needs of [[diabetic]] patients. Monitor [[blood glucose level]]s of insulin-dependent patients regularly during long-term treatment.

== References ==
{{Reflist|2}}


{{Antipsychotics}}
{{Cholinergics}}
{{Dopaminergics}}
{{Histaminergics}}
{{Piperazines}}
{{Tricyclics}}

[[Category:Phenothiazines]]
[[Category:Typical antipsychotics]]
[[Category:Piperazines]]
[[Category:Treatment of bipolar disorder]]
[[Category:Organochlorides]]
[[Category:Alcohols]]

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[[Category:2Fix]]