Antipsychotic Drugs

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Aetna Intelihealth InteliHealth Aetna Intelihealth Aetna Intelihealth
 
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Harvard Medical School
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Antipsychotic Drugs

Depression
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What Kind Of Treatment Is Available?
Antipsychotic Drugs
Antipsychotic Drugs
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Antipsychotic drugs treat the unrealistic ideas that can appear during depression or mania.
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InteliHealth
2011-04-24
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InteliHealth/Harvard Medical Content
2014-04-15

Reviewed by the Faculty of Harvard Medical School

Antipsychotic Drugs
 

Distorted or unrealistic thinking (psychosis) can be a symptom of depression. Antipsychotic drugs treat psychotic symptoms. Psychotic symptoms are unrealistic ideas. Examples are delusions (false beliefs) and hallucinations (false perceptions). They can appear in a number of psychiatric disorders, including mood disorders and schizophrenia.

Antipsychotic drugs tend to be divided into two broad groups based on when they were first introduced.

  • First generation (or "typical") antipsychotic drugs were discovered in the 1950s. They include chlorpromazine, haloperidol, perphenazine, and fluphenazine. Typical antipsychotics are more likely than so-called atypical antipsychotics to cause side effects that involve physical movements, such as muscle spasms, tremor or restlessness.
  • Second generation (or "atypical") antipsychotic drugs (for example, olanzapine and risperidone) are newer and have become the first choice for treating psychosis. Many patients find the side effects of these newer drugs easier to tolerate, but there are risks. Sometimes atypical antipsychotic drugs cause weight gain and may increase the risk for diabetes. Recent research has questioned whether these medications are any more effective than older antipsychotics. The newest ones are certainly more expensive. Nonetheless, they are now commonly prescribed ahead of first-generation antipsychotics.

Antipsychotic drugs also can be used in very low doses to enhance the effect of antidepressants. At low doses, antipsychotic drugs are less likely to cause the most troubling or harmful effects. Antipsychotic drugs can also be combined effectively with mood stabilizers.

Important Warnings About All Antipsychotic Drugs

 
Any antipsychotic drug can cause both serious and less troubling side effects. Be particularly alert to the following:
 
Tardive dyskinesia. In tardive dyskinesia, involuntary muscle contractions cause unwanted movements, often of the facial muscles and tongue, and sometimes of the upper body, arms and legs. These movements generally occur after several months or years of treatment. (The word "tardive" means late.) Tardive dyskinesia is sometimes irreversible; it usually goes away if it is caught early and the drug dose is lowered or the drug is stopped.
 
There is evidence that tardive dyskinesia is less common with atypical antipsychotics.
 
Neuroleptic Malignant Syndrome. This rare but dangerous condition is more common with high doses of first-generation antipsychotic drugs. A high fever develops over hours or days. Muscles become rigid, heart rate goes up and confusion ensues. The antipsychotic drug must be stopped immediately and treatment started, usually in the hospital, to prevent a potentially fatal outcome.
  
Weight gain and diabetes. Weight gain is a possible side effect of all antipsychotic drugs, but it seems to be more of a problem with some of the second-generation drugs. Some people develop cholesterol problems and see their blood sugar levels rise. Newer antipsychotics may increase the risk of diabetes. It is a good idea to monitor your weight and have your cholesterol and blood sugar checked regularly if you take one of these drugs.
 
Increased risk of death for elderly people with dementia. Elderly people taking second-generation antipsychotics, if they have dementia and psychosis, have a higher rate of death than people with similar problems who have been taking a placebo. The causes of death vary — they are mostly related to the cardiovascular system or to infections — so it is hard to explain how the drug increases the risk of death. This finding has led the Food and Drug Administration to withdraw its approval of these drugs for people with "dementia-related psychosis."

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Second-Generation (Atypical) Drugs
 
Newer antipsychotic drugs include:

Although it's not true in every case, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole often have more tolerable side effects than the first-generation antipsychotic drugs, and, in some ways, they may be safer. Clozapine has some troubling side effects, but also positive effects, especially in the treatment of schizophrenia. Clozapine is used less frequently in the treatment of bipolar disorder, and rarely for depression. Doses and common adverse effects are described below. If your doctor prescribes one, be sure to review in detail all the advantages and disadvantages of the drug you’re taking.

Olanzapine

Olanzapine (Zyprexa) is effective in the treatment of mania, but a mood stabilizer is also usually needed.

The starting dose is 5 to 10 milligrams, usually taken once per day, although depressed people may initially be prescribed 2.5 milligrams. The usual maximum dose is 20 milligrams per day. Most people take it before bed because of its sedating effect.
 
Olanzapine may be taken with or without food.
 
The most common side effects are drowsiness, weight gain and lower blood pressure. Other possible side effects are agitation, restlessness, trembling, constipation, dizziness, dry mouth, blurry vision and headache. This drug may cause a rise in cholesterol and blood sugar, so health care professionals should monitor these levels. Tardive dyskinesia or neuroleptic malignant syndrome can occur with olanzapine use, but the risk appears much less than with first-generation antipsychotics.
If you notice these or any other changes, talk to your doctor.

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Risperidone
 
A standard starting dose of risperidone (Risperdal) is 1 milligram per day, though it is not unusual to start with 0.25 or 0.5 milligrams when treating depression. The usual maximum dose is 6 milligrams per day. Risperidone can be taken with or without food.
 
Risperidone can cause brief drops in blood pressure at the beginning of treatment. Common side effects are a change in sleep (either trouble sleeping or sleeping more), sedation or a dulled feeling, anxiety or headache. You may be able to avoid these symptoms by starting with a low dose. Your doctor will monitor any weight gain, higher cholesterol and higher blood sugar.
 
Tardive dyskinesia or neuroleptic malignant syndrome can occur with risperidone, but the risk appears much less than with first-generation antipsychotics.
 
If you notice these or any other changes, talk to your doctor.

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Quetiapine
 
The starting dose for quetiapine (Seroquel) is 25 to 50 milligrams per day, usually in two or three doses. The usual maximum dose is 800 milligrams per day. Quetiapine can be taken with or without food.
 
Quetiapine can cause brief drops in blood pressure that can lead to dizziness or fainting. Starting treatment with a low dose (for example, 25 milligrams twice per day) can reduce this risk. Quetiapine may also cause a small increase in the risk of developing a cataract or seizures.
 
Common side effects are sleepiness (especially in the first few days of treatment). Thus, quetiapine may be used as a sleep medication. Other side effects include dizziness, dry mouth, stomach upset, constipation and weight gain. Higher cholesterol and higher blood sugar levels may occur. Tardive dyskinesia or neuroleptic malignant syndrome can occur with quetiapine, but the risk appears to be much less than with first-generation antipsychotics.
 
If you notice these or any other changes, talk to your doctor.

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Ziprasidone
 
The starting dose for ziprasidone (Geodon) is 20 milligrams twice per day, though a dose of 20 milligrams once per day may be useful for some people with depression. The usual maximum dose is 80 milligrams twice per day. Ziprasidone should be taken with food.
 
Common side effects are nausea, headache, constipation and dizziness. Some people become drowsy; others have trouble sleeping. When ziprasidone first came on the market, there were some concerns that it may cause problems to the heart's rhythm, but the risk does not appear any greater than the risk for placebo or other antipsychotic drugs. People with heart disease should discuss the risk with their doctor.
 
Ziprasidone can cause brief drops in blood pressure that can lead to dizziness or fainting. It may also cause a small increase in the risk of having a seizure. Unlike other antipsychotic drugs, ziprasidone does not appear to cause weight gain. This product does include the Food and Drug Administration's warning about high blood sugar and diabetes, so your doctor may monitor blood sugar levels from time to time.
 
Tardive dyskinesia or neuroleptic malignant syndrome can occur with ziprasidone use, but the risk appears to be less than with first-generation antipsychotics.
 
If you notice these or any other changes, talk to your doctor.

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Aripiprazole
 
The starting dose for aripiprazole (Abilify) is 5-10 milligrams per day. The usual maximum daily dose is 30 milligrams. Aripiprazole may be taken with or without food.
 
Common side effects are headache, anxiety, insomnia, restlessness, nausea and constipation. It may cause some dizziness when a person stands up from a lying or sitting position. Aripiprazole does not appear to cause weight gain to the same degree as some other atypical antipsychotics. This medication does, however, include the U.S. Food and Drug Administration's warning about high blood sugar and diabetes, so your doctor may monitor blood sugar levels from time to time.
 
Tardive dyskinesia or neuroleptic malignant syndrome can occur with aripiprazole, but the risk appears to be less than with first-generation antipsychotics.
 
If you notice these or any other changes, talk to your doctor.
 

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Paliperidone

The starting dose of paliperidone (Invega) is 3 to 6 milligrams per day, with a maximum dose of 12 milligrams per day.

The most common side effects are low blood pressure, dizziness and increased heart rate, especially if you move from sitting to standing. Fatigue, sleepiness, headache, constipation, appetite increases and sexual dysfunction can also occur.

As with other second-generation antipsychotics, your doctor will monitor any weight gain, higher cholesterol and higher blood sugar.

Tardive dyskinesia or neuroleptic malignant syndrome can occur with paliperidone use, but the risk appears to be less than with first-generation antipsychotics. 

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Lurasidone

The starting dose of lurasidone (Latuda) is 20 to 40 milligrams per day, with a maximum dose (when treating depression) of 120 milligrams per day.

The most common side effects are restlessness, agitation, upset stomach, difficulty moving (or slow movement), muscle stiffness, or tremor.

As with other second-generation antipsychotics, your doctor will monitor any weight gain, higher cholesterol and higher blood sugar.

Tardive dyskinesia or neuroleptic malignant syndrome can occur with lurasidone use, but the risk appears to be less than with first-generation antipsychotics. 

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Asenapine

The dose of asenapine (Saphris) is 5 to 10 milligrams per day. It is taken sublingually (that is, placed under the tongue), rather than swallowed. It is also generally used to treat mania (the up mood of bipolar disorder) rather than depression.

The most common side effects are temporary numbness of the mouth and tongue. Also common are drowsiness or dizziness. As with other second-generation antipsychotics, your doctor will monitor any weight gain, higher cholesterol and higher blood sugar.

Tardive dyskinesia or neuroleptic malignant syndrome can occur with asenapine use, but the risk appears to be less than with first-generation antipsychotics.

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Clozapine
 
The starting dose of clozapine (Clozaril) is 12.5 to 25 milligrams per day; the usual effective dose range is 100 to 900 milligrams per day.
 
The main danger of clozapine is a failure of the body to produce the white blood cells needed to fight infection (a condition called agranulocytosis). Clozapine treatment therefore requires monitoring of the white blood cell count. Other common side effects are drowsiness, dizziness, rapid heartbeat, constipation, stomach upset, weight gain, fever and headache.
 
Clozapine (Clozaril) is very useful for the treatment of schizophrenia, but because agranulocytosis is a very risky side effect, clozapine is usually not used unless other treatments have failed. Clozapine can be effective in some cases of bipolar disorder. It is rarely used for depression alone, except if symptoms of psychosis have been particularly resistant to other treatments.
Clozapine may cause tardive dyskinesia or neuroleptic malignant syndrome.

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First-Generation Antipsychotic Drugs
 
First-generation antipsychotic drugs are very effective. These drugs may be useful when atypical antipsychotic drugs have not been. They may be tolerated well, particularly when used in low doses or when used only for brief periods.
 
The starting doses are usually taken two or more times per day. Once a regular dose is established, however, these drugs can be taken once per day.
 

Generic Name

Brand Name

Dose

Maximum Dose

Chlorpromazine
Thorazine
10-25 milligrams per day
1,000 milligrams per day
Fluphenazine
Prolixin
1-2.5 milligrams per day
20 milligrams per day
Trifluoperazine
Stelazine
1-2 milligrams per day
30 milligrams per day
Perphenazine
Trilafon
2-4 milligrams per day
64 milligrams per day
Thioridazine
Mellaril
10-25 milligrams per day
600 milligrams per day
Haloperidol
Haldol
0.5-1 milligrams per day
15 milligrams per day
Thiothixene
Navane
1-2 milligrams per day
30 milligrams per day
Molindone
Moban
5-10 milligrams per day
100 milligrams per day
Loxapine
Loxitane
5-10 milligrams per day
100 milligrams per day
 
Common side effects are muscle stiffness, muscle spasms that can be very persistent and distressing, restlessness, tremor, reduced facial expression, sedation, weight gain, low blood pressure, dry mouth, blurred vision or constipation. Tardive dyskinesia and neuroleptic malignant syndrome are more common with first-generation antipsychotic drugs than with atypical antipsychotic drugs. If you notice these or any other changes, talk to your doctor.

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Last updated October 02, 2014


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