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The primary medications used to treat schizophrenic disorders are the antipsychotic medications, also called neuroleptics. Although these medications are not a cure for schizophrenia, they are effective in alleviating or reducing symptoms. Chlorpromazine (Thorazine), the first medication of this kind, became available for use in the United States during the early 1950s. Since its discovery, several other classes of antipsychotic medications have been developed.

All of the widely used traditional antipsychotic medications are equally effective in treating schizophrenia; however, some individuals may prefer one medication to another because they experience different side effects. Some patients may respond better or experience fewer side effects with those traditional antipsychotic medications that are available in a long-acting, injectable form. Long-acting, injectable medication may also be helpful to patients who do not take their medication reliably.

On the other hand, clozapine (Clozaril), an atypical antipsychotic medication, was first marketed in February 1990 and has been found to be superior to traditional antipsychotic medications for some patients with treatment-resistant schizophrenia. Clozapine appears to cause less muscle stiffness and restlessness (extrapyraniidal side effects) than traditional antipsychotic medications and is less likely to produce tardive dyskinesia (TD). However, close monitoring via weekly blood testing is necessary for patients who are treated with clozapine. The traditional antipsychotic medications are believed to help relieve psychotic symptoms by blocking the binding sites (receptors) for certain chemicals (neurotransmitters) found in the brain.

The neurotransmitter dopamine has been the focus of much interest in learning how many of the antipsychotic medications work. Receptors for dopamine and other chemical transmitters in the brain are targets of the antipsychotic medications, different classes of which may affect one receptor type more than another. Specific side effects may result because a particular binding site is affected by a certain medication.

One way to classify antipsychotic agents is by the dosage of medication, or the potency (strength) in milligrams, that is typically recommended. Antipsychotic agents are often classified on this basis as high, middle, or low potency. Individual doses of medication taken by patients may vary because of differences among individuals in both the severity of their illness and the rate at which they metabolize (break down) medication. This latter factor is influenced by age, race, sex, body build, diet, use of cigarettes or alcohol, and other medications being taken.

The lowest possible dosage of medication effective in relieving symptoms is usually prescribed. Sometimes symptoms of schizophrenia will flare up, requiring a temporary (weeks to months) increase in medication dosage. After an initial or acute episode of illness has been treated with medication, the doctor usually will taper the dosage very slowly to the lowest possible level necessary to keep the symptoms from returning. In a few circumstances, especially when symptoms are mild, some individuals may not require medication. Others may be able to use very low doses except when symptoms are severe. Because of all these factors, it is important that patients consult with their doctor before making changes in medication dose.

Can a patient become addicted to antipsychotic medications?
Addiction to antipsychotic medications does not occur. However, some individuals who have taken such medications for more than a few weeks experience mild, unpleasant symptoms such as nausea, vomiting, abdominal cramps, diarrhea, or sweating when the medication is abruptly stopped. If it becomes necessary to stop medication, the dosage should be slowly tapered to avoid an increase in psychotic symptoms or the effects mentioned above.

How long will a patient have to take antipsychotic medication?
Duration of therapy with antipsychotic medication is highly individual. Most patients with chronic schizophrenia require some type of medication, usually antipsychotic, for most of their lives. However, some individuals, especially those who have insight into the nature of their illness and understand that increased symptoms may be a warning sign for relapse, are able to take a reduced dose or discontinue medication periodically.

What are the major side effects of antipsychotic medications?
The side effects of antipsychotic medications are a result of their action on chemical receptors. The different classes of antipsychotic medications may affect one receptor more than another, causing different side effects. For example, the lower potency antipsychotic medications are more likely to produce sedation, dry mouth, episodic low blood pressure, and dizziness, whereas the higher potency agents are more likely to produce drooling and muscle stiffness.
Other side effects of antipsychotic medications include constipation, skin rash, sun sensitivity, cholestatic jaundice (slowing of bile flow in the liver), and lowered white blood cell count (agranulocytosis). For all of the currently available antipsychotic medications except clozapine, the risk for lowered white blood cell count is extremely low. With clozapine, however, the risk is high enough (1% to 2% during the first year) to require weekly blood cell monitoring to ensure early detection of this disorder.
Antipsychotic medications are also capable of lowering the seizure threshold. This is an especially critical side effect of clozapine, as patients taking higher doses are at greater risk for seizures than patients taking lower doses. Examples of additional important side effects are movement disorders, including muscle stiffness and TD; neuroleptic malignant syndrome; and side effects involving the reproductive system.

Questions frequently asked about the effect of antipsychotic medications on the reproductive system:
Will taking antipsychotic medications affect sexual performance?

Some men and women who take antipsychotic medications experience a lowering of their sexual drive. Antipsychotic agents may slightly lower blood levels of testosterone, the hormone responsible for maintaining the libido (sex drive) in both men and women. The lower potency antipsychotic medications, such as thioridazine (Mellaril) and chlorpromazine (Thorazine), occasionally cause delayed or retrograde ejaculation in men. During retrograde ejaculation, orgasm is reached without the simultaneous emission of semen; semen is instead propelled backwards into the bladder and eliminated with the next urination (which may appear cloudy as a result).
Will antipsychotic medications affect the menstrual cycle or the ability to have children?
Antipsychotic medications lead to an increased level of the hormone prolactin. High prolactin levels may cause irregularity or lengthening of the menstrual cycle, breast swelling, and lactation (breast milk production) in women. Breast enlargement may also occur in men taking antipsychotic medications; this is called gynecomastia. These changes are reversible when the dose of antipsychotic medication is reduced or stopped, causing prolactin levels to be lowered or return to normal.

Women with schizophrenia, regardless of their medication status, may have a lower level of fertility compared with nonschizophrenic women. Conceiving a child may be even more difficult for a woman taking antipsychotic medications because of lowered fertility or menstrual irregularities associated with such medications. Therefore, it is important for women taking these medications to discuss family planning with their doctor and other clinicians.

Do antipsychotic medications cause birth defects?

There are no birth malformations known to be caused by antipsychotic medications. Antipsychotic medications are thought to reduce symptoms of schizophrenia by helping to correct chemical imbalances in the brain; it is unknown if the changes in neurochemical levels or their receptors that occur in the brain of a developing fetus exposed to antipsychotic medications will affect the developing nervous system connections of the fetus. Further research is needed in this important area. Check with your doctor if you're planning on becoming pregnant while taking antipsychotics.

As all circumstances are not the same and each patient may have different medical and emotional needs, any woman who takes antipsychotic medications (or other medications) and considers becoming pregnant should seek advice from her physician to discuss the risks and benefits for her.

Other atypical antipsychotic medications

As a group, the atypical antipsychotic medications differ from the traditional antipsychotic medications in two ways. First, atypical antipsychotic medications are believed to produce less muscle stiffness and may be less likely to cause TD than the traditional antipsychotic agents. Accordingly, because they are less likely to produce neurological side effects, they do not compound or worsen negative symptoms such as flat affect, lack of motivation and poverty of thought and speech. Second, they do not cause an increase in the hormone prolactin. Thus, specific endocrine side effects, such as enlarged breast tissue and menstrual irregularities, occur to a much lesser extent.

Research is ongoing to develop newer, safer antipsychotic medications. Two promising medications, remoxipride and risperidone, appear to be as effective as the traditional antipsychotic medications and they may cause less muscle stiffness and other movement disorders.