Fluphenazine & Tardive Dyskinesia

Prior to 1951, standard treatment for schizophrenics and other mentally ill patients in the United States consisted of shock treatments (either by electricity or with insulin injections), or surgery (primarily frontal lobotomy, which literally destroyed the frontal lobe of the brain and left the patient in a vegetative state). This all changed in 1954, when a drug developed in Europe, called chloropromazine, was introduced. This drug was a derivative of a chemical that had been considered a form of anesthesia and used as a sedative. French psychiatrists had discovered that mental patients medicated with chloropromazine showed a decrease in symptoms. In 1954, a drug company called Smith, Kline & French, known today as GlaxoSmithKline, secured the rights to market the drug under the brand Thorazine.

Chloropromazine was not the last antipsychotic, or neuroleptic medication developed during the early days of psychopharmacology. Haloperidol was introduced by a Belgian pharmaceutical company in 1957, although it was not approved for use in the U.S. until a decade later. Another "first-generation" antipsychotic was fluphenazine which, despite being linked to causing long-term, irreversible tardive dyskinesia, continues to be marketed in the U.S. under the brand name Prolixin (Bristol-Myers Squibb) or Permitil (Novartis).

The connection between fluphenazine and tardive dyskinesia was noted rather late and the first serious study was not initiated until 1981, when a research team examined a group of 22 mental outpatients who had been receiving regular injections of the drug. When these patients were measured using the Abnormal Involuntary Movement Scale (AIMS), a strong connection between patient scores and fluphenazine dosage was noted. On the other hand, another study conducted in Canada seven years later found little difference in the rates of tardive dyskinesia between patients treated with fluphenazine and those who were not. However, it was noted that patients who did receive fluphenazine required less in the way of hospitalization.

Mechanism and Dosage

Although three "first generation" neuroleptic medications — chloropromazine, haloperidol and fluphenazine — have different chemical makeups and differ in levels of strength, the medications operate the same way, by blocking dopamine receptors and pathways. Dopamine is a chemical neurotransmitter that allows the brain to communicate with various parts of the body. Inhibiting the movement of this chemical addresses the symptoms of schizophrenia and other psychoses. Unfortunately, this also causes the types of involuntary movements associated with tardive dyskinesia and other movement disorders.

Fluphenazine is by far the most powerful of the three first generation antipsychotic drugs, which are still considered "typical," or standard treatment, despite the proven side effects, and can be up to 70 times more potent than cholorpromazine. The drug is normally administered through the use of injections every two to three weeks, generally to patients who fail to show progress or fail to take their normal medication as instructed.

Unlike haloperidol, fluphenazine is used strictly as a medication to address the symptoms of schizophrenia, manic manifestations of bipolar disorder and other psychoses. It is also occasionally used to treat symptoms of dementia.

Other Side Effects

In addition to the symptoms associated with tardive dyskinesia, use of fluphenazine has been shown to have other serious, and even fatal side effects including:

Drowsiness
Dizziness
Skin rash
Drymouth
Insomnia
Muscular weakness
Loss of appetite
Dystonia (movement difficulties)

Additional symptoms may be similar to those found in victims of Parkinson's disease, such as tremors and difficulty over control of facial muscles. These can be addressed with the use of concomitant treatment with medications used to control such symptoms.

One particular danger associated with the use of fluphenazine is neuroleptic malignant syndrome, which is essentially an allergic reaction to antipsychotic drugs. Symptoms include muscular rigidity, fever and delirium and death has been reported in up to 15 percent of cases.

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