Phenothiazines

Fluphenazine

Brand Name (Manufacturer)

Prolixin (Apothecon)

Type of Drug

Psychoactive-antipsychotic tranquilizer

Used For

Fluphenazine is used for the management of psychosis, a mental disorder characterized by difficulty thinking, recognizing reality, and acting rationally.

General Information

Fluphenazine belongs to a class of psychoactive drugs called phenothiazines. Although the mechanism by which they work is unknown, they have potent effects on the central nervous system and other organs. In addition to their effects on mental disorders, they also prolong the effects of anesthetics and other central nervous system depressants. They can reduce blood pressure, stop seizures, and prevent vomiting. Fluphenazine is more potent than most of the other phenothiazines and it is less likely to cause serious side effects.

Fluphenazine is available in a number of different chemical forms, which differ primarily in the duration of their action. The drug is available in tablets, as a solution for injection, and as an oral concentrate.

Treatment

As with all psychoactive drugs, the minimum effective dosage should be taken. The oral forms of fluphenazine are usually initially used at a range of 2.5 to 10 mg per day, divided into equal doses given at six- to eight-hour intervals. Treatment usually starts at low initial dosages and is gradually increased as necessary and tolerated. Treatment is effective for most people with doses under 20 mg daily, but some people with severe disease may require up to 40 mg per day.

When the symptoms are controlled, the dosage can generally be reduced gradually to a daily maintenance dose of 1 to 5 mg, often given as a single daily dose. After stabilization on the short-acting forms of the drug, individuals may elect to switch to the longer-acting forms to make taking the drug easier. Once monthly intramuscular injections may be appropriate once control is achieved.

Cautions and Warnings

Fluphenazine should not be used by anyone with a known allergy to it. It should also not be used by people with brain damage, those receiving large doses of other psychoactive drugs, or those in comatose or severely depressed states. The drug should also not be used by people with severe liver damage or blood disorders.

People who are allergic to other phenothiazines may also be allergic to fluphenazine and should use the drug with caution. Similarly, people who are exposed to extreme heat or phosphorus pesticides and people with a history of seizures or heart disease should use the drug with caution because of their increased risk of side effects.

Although phenothiazines are in general not addictive, some people have experienced withdrawal symptoms (including nausea, vomiting, dizziness, and tremors) when stopping therapy after receiving high doses. These symptoms may be reduced by taking an anti-Parkinson's-disease drug like benztropine.

Fluphenazine may impair the mental and physical abilities necessary to operate dangerous machinery or to drive an automobile.

Side Effects

The side effects reported most frequently after using phenothiazines include loss of muscle coordination or tone, muscle rigidity, and other disorders of the nerve control of muscles. In general, the symptoms are reversible when treatment is stopped or benztropine is used, but in some cases they may persist.

Tardive dyskinesia is a special neuromuscular side effect of phenothiazines. It is characterized by potentially irreversible, involuntary muscle movements that usually involve the tongue, face, mouth, lips, jaw, torso, and extremities. Although the side effect occurs most frequently among the elderly (especially elderly women), it is not possible to predict whether an individual will develop the disorder. The risk of the side effect and the likelihood it will be irreversible are believed to be increased with increased duration of treatment and cumulative dose.

Antipsychotic drugs, including fluphenazine, can cause a potentially fatal side effect called neuroleptic malignant syndrome. The syndrome is characterized by high fever, muscle rigidity, altered mental status, irregular pulse or blood pressure, and abnormal heart rhythms. If these symptoms occur, the drug should be stopped and a physician contacted immediately.

Other side effects of fluphenazine include low blood pressure or fluctuations in blood pressure, weight change, swelling in the extremities, allergic reactions, and liver damage.

Pregnancy/Breast-Feeding

Fluphenazine has not been formally studied in pregnant women. Most evidence suggests, however, that phenothiazines have a low risk of causing birth defects or other fetal harm when used during pregnancy. Pregnant women are encouraged to discuss the benefits and potential risks of fluphenazine with their physician before deciding to use the drug.

HIV may be passed from a woman to her child through breast milk. In areas where nutritional alternatives are readily available, breast-feeding is discouraged for HIV-positive women. It is not known whether fluphenazine is excreted in human milk. Other phenothiazines have not had serious adverse effects on nursing infants, but whether this would be true for fluphenazine is not known.

Use In Children

Fluphenazine has not been formally studied in children, and there are no recommendations regarding its use for them.

Use in the Elderly

Older adults may be more susceptible to the side effects of the drug and may require reduced doses.

Drug Interactions

Fluphenazine may intensify the effects of alcohol, analgesics, narcotics, antihistamines, and barbiturates. Antacids may decrease absorption of fluphenazine. Phenobarbital or lithium may decrease the effect of fluphenazine. Guanethidine or methyldopa used with fluphenazine may cause increased blood pressure. Use of insulin with fluphenazine may result in increased blood-sugar levels. Use of orphenadrine with fluphenazine may result in lowered blood-sugar levels.

Food Interactions

None reported.

Other Drugs Used for Similar Conditions

A number of different drugs are available for treating psychosis. They include chlorpromazine, thioridazine, trifluoperazine, haloperidol, loxapine, and thiothixene. They differ in their duration of action, side effects, dosage, and administration. Because different people respond differently to each of the drugs, the choice of therapy usually comes down to finding through trial and error a drug that is both effective and tolerable. In comparison to the others, fluphenazine has relatively mild effects on alertness and blood pressure, but it has a relatively high risk of causing neuromuscular side effects.

Perphenazine

Brand Names (Manufacturers)

Trilafon (Schering)
Perphenazine + Amitriptyline: Etrafon (Schering); Triavil (Merck)

Type of Drug

Psychoactive-antinausea, antivomiting, antipsychosis drug

Used For

Perphenazine is used to treat severe nausea and vomiting. It is also used to treat the symptoms of psychosis.

General Information

Perphenazine belongs to a class of psychoactive drugs called phenothiazines. Although the mechanism by which they work is unknown, they have potent effects on the central nervous system and other organs. They can reduce blood pressure, stop seizures, control nausea and vomiting, and control the symptoms of psychosis, a mental disorder characterized by difficulty thinking, recognizing reality, and acting rationally.

Perphenazine is available as tablets, oral concentrate, and solution for injection. It is also available in a number of combination products with the tricyclic antidepressant amitriptyline.

Treatment

The dosage is individualized and adjusted for each person's response. As with all psychoactive drugs, the lowest effective dose should be used to reduce the risk of side effects. The drug is generally started at a low dosage and increased as necessary and as tolerated. Adults usually take 8 to 16 mg a day, in divided doses for the treatment of nausea and vomiting. Doses up to 24 mg per day may be necessary. As soon as possible, the dosage should be reduced. Higher doses are used for the treatment of psychosis.

The oral concentrate should not be mixed with beverages containing caffeine (coffee, cola, etc.), tannic acid (tea), or pectinates (apple juice). It may be diluted with water, saline, homogenized milk, carbonated orange or pineapple drinks, apricot, prune, orange, tomato, or grapefruit juices.

Cautions and Warnings

Perphenazine should not be used by anyone with a known allergy to it. It should also not be used by people in comas, those with fevers above 104F, suspected or established brain damage, liver damage, or suppressed bone-marrow activity (as may occur when using AZT, ganciclovir, alpha interferon, or other drugs).

Perphenazine may increase the risk of seizures and should be used with caution in people with a history of seizures and those experiencing alcohol withdrawal symptoms.

Perphenazine may impair the mental and physical abilities necessary to operate an automobile or dangerous machinery.

Phenothiazines elevate blood levels of prolactin, a hormone involved in the production of breast milk. Because many breast cancers are stimulated by prolactin, perphenazine may aggravate existing breast cancers, but there is no evidence that it increases the risk of developing breast cancer.

Perphenazine should be used with caution by people who are exposed to phosphorus insecticides or extreme heat, because of the risk of serious side effects.

Side Effects

Drowsiness, stuffy nose, dizziness, blurred vision, tremors, and constipation are common side effects of perphenazine.

Tardive dyskinesia is a special neuromuscular side effect of phenothiazines. It is characterized by potentially irreversible, involuntary muscle movements that usually involve the tongue, face, mouth, lips, jaw, torso, and extremities. Although the side effect occurs most frequently among the elderly (especially elderly women), it is not possible to predict whether an individual will develop the disorder. The risk of the side effect and the likelihood it will be irreversible are believed to be increased with increased duration of treatment and cumulative dose.

Other neuromuscular side effects of phenothiazines include agitation, insomnia, muscle spasm, difficulty swallowing, and shuffling gait, among others.

Antipsychotic drugs, including perphenazine, can cause a potentially fatal side effect called neuroleptic malignant syndrome. The syndrome is characterized by high fever, muscle rigidity, altered mental status, irregular pulse or blood pressure, and abnormal heart rhythms. If these symptoms occur, the drug should be stopped and a physician contacted immediately.

Other side effects of perphenazine include low blood pressure or fluctuations in blood pressure, weight change, swelling in the extremities, allergic reactions, high fever, darkening of the skin, impaired vision, muscle weakness, and liver damage. In some cases, the drug has caused deficiencies in white blood cell counts.

Pregnancy/Breast-Feeding

Perphenazine has not been formally studied in pregnant women. It is usually not prescribed during pregnancy because its effects on the fetus are uncertain. Pregnant women are encouraged to discuss the benefits and potential risks of perphenazine with their physician before deciding to use the drug.

HIV can be passed from a woman to her child through breast milk. In areas where nutritional alternatives are readily available, breast-feeding is discouraged for HIV-positive women. Perphenazine is excreted in human milk, but its effects on nursing infants are not well understood.

Use In Children

Perphenazine is not recommended for children under twelve, because its safety and effectiveness in this population have not been studied or established.

Use in the Elderly

Older adults may be more susceptible to the side effects of the drug and may require reduced doses.

Drug Interactions

Perphenazine and other central nervous system depressants (narcotic analgesics, alcohol, antihistamines, sleeping pills, tranquilizers, and some antidepressants) may enhance the depressing effect of each other.

The use of alcohol with perphenazine may result in severe low blood pressure.

Antacids (including those in ddI tablets or powder) may interfere with absorption of perphenazine into the body. Perphenazine should be taken one hour before or after taking an antacid.

Food Interactions

Perphenazine may be taken with or without food. Foods with caffeine may interfere with the effects of perphenazine and should be avoided while taking the drug.

Other Drugs Used for Similar Conditions

For treatment or prevention of nausea and vomiting, a number of different types of drugs are available. Drugs used include metoclopramide, antihistamines (e.g., dimenhydrinate, meclizine, and promethazine), phenothiazines (e.g., prochlorperazine or thiethylperazine), granisetron, or ondansetron. The different types of drugs differ significantly in their side effects, and the choice of therapy is often determined by the side effects for which an individual is at risk.

Thioridazine

Brand Names (Manufacturers)

Mellaril (Sandoz); Mellarzine (Major)

Type of Drug

Psychoactive-phenothiazine antipsychotic

Used For

Thioridazine is primarily used to treat the symptoms of psychosis. It is also used to treat depression and anxiety, especially in older adults. In children, it is used to treat hyperactivity that results in impulsivity, difficulty sustaining attention, aggressivity, wide emotional swings, and poor tolerance for frustration.

General Information

Thioridazine belongs to a class of psychoactive drugs called phenothiazines. Although the mechanism by which they work is unknown, they have potent effects on the central nervous system and other organs. They can reduce blood pressure, stop seizures, control nausea and vomiting, and control the symptoms of psychosis, a mental disorder characterized by difficulty thinking, recognizing reality, and acting rationally.

Thioridazine is particularly useful in treating the elderly because it is less likely to cause abnormal shaking movements than other phenothiazines. Its major disadvantage is that it can cause vision problems when taken at high doses for long periods.

Thioridazine is available as tablets, oral solution, and oral suspension.

Treatment

The dosage is individualized and adjusted for each person's response. As with all psychoactive drugs, the lowest effective dose should be used to reduce the risk of side effects. The drug is generally started at a low dosage and increased as necessary and as tolerated. For treatment of psychosis in adults, the starting dose is usually 50 to 100 mg, taken three times a day, with a gradual increase to a maximum of 800 mg daily if necessary. As soon as possible, the dosage should be reduced.

The initial adult dosages for treatment of depression and anxiety, agitation, tension, sleep disturbances, or fear is 25 mg taken three times a day. The total daily dosage usually does not exceed 200 mg.

Cautions and Warnings

Thioridazine should not be used by anyone with a known allergy to it. It should also not be used by people in comas or those with severely elevated or suppressed blood pressure.

Phenothiazines may increase the risk of seizures and should be used with caution in people with a history of seizures and those experiencing alcohol withdrawal symptoms.

Thioridazine may impair the mental and physical abilities necessary to operate an automobile or dangerous machinery.

Phenothiazines elevate blood levels of prolactin, a hormone involved in the production of breast milk. Because many breast cancers are stimulated by prolactin, thioridazine may aggravate existing breast cancers, but there is no evidence that it increases the risk of developing breast cancer.

Thioridazine should be used with caution by people who are exposed to phosphorus insecticides or extreme heat because of the risk of serious side effects.

Side Effects

The most common side effects of thioridazine include drowsiness, dry mouth, and stuffy nose. Less frequently, blurred vision, muscle stiffness, loss of balance, dizziness, abnormal shaking or tremors, constipation, nausea, vomiting, diarrhea, loss of color, allergic reactions, and fainting occur. Hyperactivity, lethargy, restlessness, and headache have been rarely reported.

Tardive dyskinesia is a special neuromuscular side effect of phenothiazines. It is characterized by potentially irreversible, involuntary muscle movements that usually involve the tongue, face, mouth, lips, jaw, torso, and extremities. Although the side effect occurs most frequently among the elderly (especially elderly women), it is not possible to predict whether an individual will develop the disorder. The risk of the side effect and the likelihood it will be irreversible are believed to be increased with increased duration of treatment and cumulative dose.

Antipsychotic drugs, including thioridazine, can cause a potentially fatal side effect called neuroleptic malignant syndrome. The syndrome is characterized by high fever, muscle rigidity, altered mental status, irregular pulse or blood pressure, and abnormal heart rhythms. If these symptoms occur, the drug should be stopped and a physician contacted immediately.

Pregnancy/Breast-Feeding

Thioridazine has not been formally studied in pregnant women. In limited clinical use, it has prolonged labor when taken near delivery. Pregnant women are encouraged to discuss the benefits and potential risks of thioridazine with their physician before deciding to use the drug.

HIV can be passed from a woman to her child through breast milk. In areas where nutritional alternatives are readily available, breast-feeding is discouraged for HIV-positive women. Thioridazine may pass through breast milk and cause side effects in newborns. Because of this potential toxicity, women are encouraged to consider alternatives to breast-feeding while using the drug.

Use In Children

Thioridazine is not intended for children under two years of age. For children between two and twelve years of age, dosages range from 0.5 to 3.0 mg per kg of body weight per day. The dosage is usually started at 10 mg two or three times a day and increased as necessary and tolerated.

Use in the Elderly

Older adults may be more susceptible to the side effects of thioridazine, and they may require reduced dosages. However, thioridazine is less likely than many other phenothiazines to cause side effects in elderly people.

Drug Interactions

Thioridazine may intensify the effects of other central nervous system depressants, including alcohol, antihistamines, narcotic pain relievers, sedatives, and barbiturates. Thioridazine may also intensify the effects of atropine or phosphorus insecticides.

Thioridazine greatly increases blood levels of propranolol, potentially increasing the risk of its side effects. Concurrent use of pindolol and thioridazine have resulted in higher blood levels of both drugs.

Food Interactions

None reported.

Other Drugs Used for Similar Conditions

Haloperidol and a number of other phenothiazines (including chlorpromazine, fluphenazine, perphenazine, and prochlorperazine) are used to treat symptoms of psychosis. For the treatment of depression or anxiety, a wide variety of different types of drug are available. The choice of drug usually depends on the disorder, the overall condition of the individual, and other drugs being concurrently taken.

Trifluoperazine

Brand Name (Manufacturer)

Stelazine (Smithkline Beecham)

Type of Drug

Psychoactive-phenothiazine antipsychotic/antianxiety drug

Used For

Trifluoperazine is used to treat the symptoms of psychotic disorders and for the short-term management of anxiety.

General Information

Trifluoperazine belongs to a class of psychoactive drugs called phenothiazines. Although the mechanism by which they work is unknown, they have potent effects on the central nervous system and other organs. They can reduce blood pressure, stop seizures, control nausea and vomiting, and control the symptoms of psychosis, a mental disorder characterized by difficulty thinking, recognizing reality, and acting rationally.

Trifluoperazine is available as tablets, solution for injection, and concentrate for oral administration.

Treatment

The dosage of trifluoperazine must be adjusted for each person's response. Most people will use the tablets. The injectable solution is usually reserved for hospitalized patients, and the concentrate is designed for severe conditions when oral medication is preferred but the tablets are impractical.

As with all psychoactive drugs, the lowest effective dose should be used to reduce the risk of side effects. The drug is generally started at a low dosage and increased as necessary and as tolerated. For treatment of psychosis in adults, the starting dose is usually 2 to 5 mg, taken two times a day, with a gradual increase as necessary. Most people respond to 15 to 20 mg a day, but some people require as much as 40 mg per day. For treatment of anxiety in adults, the usual dosage is 1 to 2 mg, taken twice daily, up to a maximum of 6 mg per day. The drug should not be taken for longer than twelve weeks for the treatment of anxiety.

Cautions and Warnings

Trifluoperazine should not be used by anyone with a known allergy to it or any other phenothiazine drug. It should also not be used by anyone with severe central nervous system depression, severe bone-marrow suppression, or liver damage.

Trifluoperazine may impair the mental and physical abilities necessary to operate an automobile or dangerous machinery.

Phenothiazines elevate blood levels of prolactin, a hormone involved in the production of breast milk. Because many breast cancers are stimulated by prolactin, trifluoperazine may aggravate existing breast cancers, but there is no evidence that it increases the risk of developing breast cancer.

Trifluoperazine should be used with caution by people who are exposed to phosphorus insecticides or extreme heat because of the risk of serious side effects.

Trifluoperazine concentrate contains sodium bisulfite and should be used with caution in people with sulfite allergies.

The antivomiting effect of trifluoperazine may mask the symptoms of other drugs and may obscure the diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor, and Reye's syndrome.

Trifluoperazine should be used with caution in people with glaucoma because the drug can exacerbate the condition. Trifluoperazine may increase the risk of seizures and should be used with caution in people with a history of seizures.

Side Effects

Drowsiness, dizziness, skin reactions, rash, dry mouth, insomnia, irregular periods, fatigue, muscular weakness, loss of appetite, abnormal lactation, blurred vision, or involuntary muscle movements may occur in people taking trifluoperazine.

Tardive dyskinesia is a special neuromuscular side effect of phenothiazines. It is characterized by potentially irreversible, involuntary muscle movements that usually involve the tongue, face, mouth, lips, jaw, torso, and extremities. Although the side effect occurs most frequently among the elderly (especially elderly women), it is not possible to predict whether an individual will develop the disorder. The risk of the side effect and the likelihood it will be irreversible are believed to be increased with increased duration of treatment and cumulative dose.

Antipsychotic drugs, including trifluoperazine, can cause a potentially fatal side effect called neuroleptic malignant syndrome. The syndrome is characterized by high fever, muscle rigidity, altered mental status, irregular pulse or blood pressure, and abnormal heart rhythms. If these symptoms occur, the drug should be stopped and a physician contacted immediately.

Pregnancy/Breast-Feeding

Trifluoperazine has not been formally studied in pregnant women. In limited clinical experience it has caused severe side effects in the newborns of women who took the drug during pregnancy. In addition, in animal studies it caused birth defects when administered at high doses. Pregnant women are encouraged to discuss the benefits and potential risks of trifluoperazine with their physician before deciding to use the drug.

HIV can be passed from a woman to her child through breast milk. In areas where nutritional alternatives are readily available, breast-feeding is discouraged for HIV-positive women. Phenothiazines are known to pass into human milk. Because of the potential toxicity of the drug, women are encouraged to consider alternatives to breast-feeding while using it.

Use In Children

Trifluoperazine is used in children older than six years of age. The dosage of the drug should be adjusted for the weight of the child and the severity of the symptoms. The starting dosage is 1 mg administered once or twice a day. The dosage should gradually be increased until the symptoms are controlled or side effects become troublesome.

Use in the Elderly

In general, the elderly use the lower range of adult doses because they may be more susceptible to the side effects of the drug. The initial dose should be low and increased even more gradually than for younger adults.

Drug Interactions

Trifluoperazine may intensify the effect of other central nervous system depressants, including alcohol, antihistamines, narcotic pain relievers, tranquilizers, and sedatives.

Phenothiazines, including trifluoperazine, may interfere with the action of blood thinners such as warfarin or drugs used to treat blood pressure (e.g., guanethidine). Concomitant use of propranolol and trifluoperazine may increase blood levels of both drugs, potentially increasing the risk of side effects.

Use of trifluoperazine with thiazide diuretics may increase the risk of severe low blood pressure.

Phenothiazines may increase the risk of seizures, requiring dosage modifications of anticonvulsant drugs, such as phenobarbital, phenytoin, or carbamazepine. Trifluoperazine may increase blood levels of phenytoin, potentially increasing the risk of its side effects.

Food Interactions

Trifluoperazine may be taken with or without food. The oral concentrate should be diluted in tomato or fruit juice, milk, orange syrup, carbonated beverages, coffee, tea, or water. Semisolid foods such as soup or puddings may also be used.

Other Drugs Used for Similar Conditions

Haloperidol and a number of other phenothiazines (including chlorpromazine, fluphenazine, perphenazine, and prochlorperazine) are used to treat symptoms of psychosis. For the treatment of anxiety, a wide variety of different types of drug are available, including the benzodiazepines (alprazolam, chlordiazepoxide, diazepam, lorazepam, or oxazepam). Phenothiazines, including trifluoperazine, are generally not the first drug used to treat anxiety because their side effects are more severe than those of the benzodiazepines. Ultimately, the drug chosen depends on the disorder, the overall condition of the individual, and other drugs being concurrently taken.