Fixed combinations of perphenazine and the tricyclic antidepressant amitriptyline in different proportions of weight exist (see Etrafon below).

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.

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.

[citation needed] Perphenazine has sedating and anxiolytic properties, making the drug useful for the treatment of agitated psychotic patients.

A valuable off-label indication is the short-time treatment of hyperemesis gravidarum, in which pregnant women experience violent nausea and vomiting.

Perphenazine is used to treat psychosis (e.g. in people with schizophrenia and the manic phases of bipolar disorder and OCD).

[10][11] 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.

Compared with the highpotent typical antipsychotic drug haloperidol (50-fold), it despite is considered by some to have similar extralyramidalmotoric side-effects.

A brand name in Europe is Decentan pointing to the fact that perphenazine is approximately 10-times more potent than chlorpromazine.

The incidence of hypotension, sedation and extrapyramidal side-effects may be higher compared to oral treatment.

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.

Perphenazine intensifies the central depressive action of drugs with such activity (tranquilizers, hypnotics, narcotics, antihistaminics, OTC-antiemetics etc.).