Fluphenazine

Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication of the phenothiazine class. It is used in the treatment of chronic psychoses such as schizophrenia, and is about equal in effectiveness to low-potency antipsychotics like chlorpromazine. It is also used to treat depression in combination with nortriptyline. In addition to the oral form, fluphenazine comes in decanoate and enanthate depot injection versions for increased adherence. Fluphenazine is given by mouth, intramuscularly, or just under the skin.

Common side effects include movement problems, sleepiness, depression and increased weight. Serious side effects may include neuroleptic malignant syndrome, low white blood cell levels, and the potentially permanent movement disorder tardive dyskinesia. In older people with psychosis as a result of dementia it may increase the risk of dying. It may also increase prolactin levels which may result in milk production, enlarged breasts in males, impotence, and the absence of menstrual periods. It is unclear if it is safe for use in pregnancy. Fluphenazine decanoate should not be used by people with severe depression. In up to 40% of those on long term phenothiazines, liver function tests become mildly abnormal.

Fluphenazine is a dopamine antagonist, blocking mesolimbic dopamine receptors. Fluphenazine inhibits tubulin polymerization, a property shared with other phenothiazine derivatives including perphenazine, chlorpromazine, trifluoperazine, and triflupromazine.

Fluphenazine was the third antipsychotic FDA approved in the United States in 1959, and 9 years later was the first FDA approved injectable antipsychotic. The injectable form is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. It was discontinued in Australia in 2017.