Phenothiazine Antipsychotics

Phenothiazine antipsychotics are medications used to treat schizophrenia and manifestations of psychotic disorders. Some phenothiazine antipsychotics, like prochlorperazine and chlorpromazine, are used for nausea, vomiting, and hiccups.

Although, the exact mechanism of phenothiazine antipsychotics is unknown, scientists believe that they may work by blocking the action of dopamine in the brain. Dopamine is a neurotransmitter (chemical) that nerves use to communicate with one another. Phenothiazine antipsychotics are used when patients do not respond to other antipsychotics.

Examples of phenothiazine antipsychotics are:

• prochlorperazine (Compazine, Compro, Procomp),
• chlorpromazine (Promapar, Thorazine),
• fluphenazine (Permitil, Prolixin),
• perphenazine,
• trifluoperazine (Stelazine),
• thioridazine (Mellaril), and
• mesoridazine (no longer available in the United States).

There are many side effects of phenothiazine antipsychotics. Common side effects include:

• drowsiness,
• dizziness,
• headache,
• low blood pressure, and
• blurred vision.

Phenothiazine antipsychotics may cause extra-pyramidal symptoms such:

• as abnormal muscle contractions,
• difficulty breathing and swallowing,
• neck spasms, and
• movement abnormalities on face, arms, and legs.

Constipation also is common.

Phenothiazine antipsychotics can also cause neuroleptic malignant syndrome (NMS), which include symptoms of:

• fever,
• muscle rigidity,
• altered mental status,
• irregular blood pressure, and
• irregular heart rate and rhythm.

All phenothiazine antipsychotics carry a boxed warning of increased deaths in elderly patients when used for dementia-related psychosis.

Phenothiazine antipsychotics should not be combined with other antipsychotics or medications that cause extra-pyramidal side effects and neuroleptic malignant syndrome due to an increased likelihood of these side effects.

Phenothiazine antipsychotics should be used with caution with medications (for example, fluoxetine [Prozac, Sarafem, Prozac Weekly]) that reduce the activity of liver enzymes that eliminate phenothiazines because levels of phenothiazines can increase and lead to more side effects.

Phenothiazines affect heart rhythm and the risk of abnormal heart rhythms, especially when they are combined with other drugs that also affect heart rhythm. Examples include:

• amiodarone (Cordarone),
• fluconazole (Diflucan),
• itraconazole (Sporanox),
• nortriptyline (Pamelor, Aventyl), and
• many other drugs.

• All phenothiazine antipsychotics are available in oral tablet form.
• Prochlorperazine also is available as a rectal suppository.
• Fluphenazine and mesoridazine are available as injections.
• Fluphenazine and mesoridazine are available in oral liquid form.

Safe and effective use of phenothiazine antipsychotics during pregnancy has not been established. Newborns exposed to phenothiazine antipsychotics are at risk for extrapyramidal and withdrawal symptoms following delivery. Phenothiazine antipsychotics should only be used if clearly needed when benefits outweigh potential risks to the fetus.

Phenothiazine antipsychotics may enter breast milk; therefore, they should be used with caution in women who are breastfeeding. To avoid potential risks to the newborn, a decision should be made whether to discontinue the drug or to discontinue nursing.