Perphenazine
Encyclopedia
Perphenazine is a typical antipsychotic
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
; thus perphenazine is considered a medium-potency antipsychotic.
and hypotension
without loss of therapeutic activity.
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, but two recent, large-scale studies found no difference between perphenazine and the atypical antipsychotics.
In low doses it is used to treat 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. 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.
Perphenazine has sedating and anxiolytic
properties, making the drug useful for the treatment of agitated psychotic patients and, in high doses (up to 100 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.
. 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. Perphenazine causes early and late extrapyramidal side effects more often than placebo
, and at a similar rate to other medium-potency antipsychotics and the atypical antipsychotic risperidone
.
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.
Similarly to other potent antipsychotics, long-term use has been associated with cognitive decline and permanent brain damage.
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.
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 may be masked due to the strong antivertignosic effect of perphenazine. Avoid the concomitant use, too.
In general, all neuroleptics may lead to seizures in combination with the opioid tramadol (Ultram).
Perphenazine may increase the insulin
needs of diabetic patients. Monitor blood glucose levels of insulin-dependent patients regularly during long-term treatment.
Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
drug
Psychoactive drug
A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...
. Chemically, it is classified as a piperazinyl phenothiazine
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
. It has been in clinical use for decades.
Perphenazine is roughly five times as potent as chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
; thus perphenazine is considered a medium-potency antipsychotic.
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 sedationSedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
and hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
without loss of therapeutic activity.
Uses
Perphenazine is used to treat psychosis (e.g. in schizophrenics) and the manicManic
Manić is a suburban settlement of Belgrade, the capital of Serbia. It is located in the municipality of Barajevo.Manić developed on the eastern slopes of the Kosmaj mountain...
phases of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. 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, but two recent, large-scale studies found no difference between perphenazine and the atypical antipsychotics.
In low doses it is used to treat agitated depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
(together with an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
). Fixed combinations of perphenazine and the tricyclic antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
amitriptyline
Amitriptyline
Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
in different proportions of weight exist (see Etrafon below). When treating depression, perphenazine is discontinued as fast as the clinical situation allows. Perphenazine has no intrinsic antidepressive activity. Several studies show that the use of perphenazine with fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(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
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
action of perphenazine attenuates fluoxetine-induced nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
(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.
Perphenazine has sedating and anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
properties, making the drug useful for the treatment of agitated psychotic patients and, in high doses (up to 100 mg per day), for patients with life-threatening (febrile) catatonia
Catatonia
Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....
, 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
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...
and correction of electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s and fluids in the body.
A valuable off-label indication is the short-time treatment of hyperemesis gravidarum
Hyperemesis gravidarum
Hyperemesis gravidarum is a severe form of morning sickness, with "unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids." Hyperemesis is considered a rare complication of pregnancy but, because nausea and vomiting during pregnancy exist...
, 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 chlorpromazineChlorpromazine
Chlorpromazine is a typical antipsychotic...
. A 2005 systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
of the data on perphenazine conducted by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
concluded that "there were no convincing differences between perphenazine and other antipsychotics" in the incidence of adverse effects. Perphenazine causes early and late extrapyramidal side effects more often than placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
, and at a similar rate to other medium-potency antipsychotics and the atypical antipsychotic risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
.
When used for its strong antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
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
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
is a risk.
Similarly to other potent antipsychotics, long-term use has been associated with cognitive decline and permanent brain damage.
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 5-times more potent than chlorpromazine. Usual oral forms are tablets (2, 4, 8, 16 mg) and liquid concentrate (4 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
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
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 may be masked due to the strong antivertignosic effect of perphenazine. Avoid the concomitant use, too.
In general, all neuroleptics may lead to seizures in combination with the opioid tramadol (Ultram).
Perphenazine may increase the insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
needs of diabetic patients. Monitor blood glucose levels of insulin-dependent patients regularly during long-term treatment.