Seven atypical antipsychotic drugs are currently approved in the United States:
Clozapine was the first atypical drug approved (in 1989), and paliperodine the most recent approved (in 2007). Clozapine appears to have more side effects than the other atypical antipsychotics. Most of these drugs come in pill form, but some may come in liquid form or as an injection. In general, it may take up to 6 months before an atypical drug has an effect.
The atypical antipsychotics zotepine (Zoleptil) and amisulpride (Solian) are not approved for use in the United States.
Benefits of Atypical Antipsychotics.
Atypical antipsychotics have some significant limitations and complications, and their benefits compared to each other and to other antipsychotics are not always clear-cut. In-depth comparative studies are needed to determine which specific drugs are more effective and have fewer side effects than others.
Side Effects of Atypical Antipsychotics.
The following are more severe side effects or complications that may occur with these drugs:
All atypical antipsychotic drugs carry a “black box” warning on their prescribing labels advising that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The U.S. Food and Drug Administration (FDA) recommends that:
There may also be an increased background risk of diabetes in patients with schizophrenia. As a precaution, many doctors advise that all patients treated with atypical antipsychotics receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment. Patients should also have their lipid and cholesterol levels monitored. [For more information, see In-Depth Report #60: Diabetes - type 2.]
The standard typical antipsychotic drug used for schizophrenia is haloperidol (Haldol). Others include:
Studies have not shown any significant difference in benefits among these drugs.
The beneficial impact of these drugs is greatest on psychotic symptoms, particularly hallucinations and delusions in the early and midterm stages of the disorder. They are not very successful in reducing negative symptoms. Because of their significant side effects, many patient's stop taking the drug.
Depot therapy (long-lasting monthly injections, usually of haloperidol or fluphenazine) has been used with success in people who have difficulty complying with a daily regimen of these drugs. Researchers are studying low-dose regimens to discover if they can be effective and cause fewer side effects.
Side Effects of Typical Antipsychotics. These drugs can have adverse side effects related to many organs and systems in the body. These drugs are also known as neuroleptics, a name that comes from the severe neurological side effects that these medications can cause. Side effects include:
In general, higher potency drugs cause less drowsiness and drops in blood pressure but pose a higher risk for extrapyramidal side effects. Lower-potency drugs (such as chlorpromazine, thioridazine) are more sedating and have milder side effects.
Nearly every drug used to date for schizophrenia can cause extrapyramidal side effects to some degree. These side effects involve the nerves and muscles controlling movement and coordination.
Description of Extrapyramidal Side Effects. These effects resemble some of the symptoms of Parkinson's disease and include the following conditions:
Treatment of Extrapyramidal Side Effects. In general, if extrapyramidal side effects occur from neuroleptic drugs, the doctor may first try to reduce the dosage or switch to an atypical drug. Other approaches to reduce these symptoms include:
Antidepressants. Antidepressants are recommended along with antipsychotics to alleviate the depression that is so common in people with schizophrenia. One study indicated that taking antidepressants may even help prevent relapse. In spite of their benefits, fewer than half of all patients take these medications.
Anti-Anxiety Drugs. Benzodiazepines are drugs normally used to treat anxiety. They also have some modest effect on psychotic symptoms. They may be useful in the early stages of a psychotic relapse for preventing a full attack. They also are sometimes used to treat the restlessness and agitation that can occur with the use of neuroleptics. Severe side effects, including respiratory arrest, very low blood pressure, and loss of consciousness, have been reported in a few people taking anti-anxiety medication and clozapine. There is no evidence, however, of a clear danger associated with the use of these two drugs. In any case, prolonged use of anti-anxiety drugs is generally not recommended in schizophrenia. Withdrawal from these drugs should occur gradually.
Lithium. Lithium, ordinarily used for bipolar disorder, is useful for some schizophrenic patients. It appears to help those with fewer negative symptoms and without a family history of schizophrenia. However, there are no reliable criteria to predict who will benefit.
Anti-Epileptic Drugs. Drugs ordinarily prescribed for epilepsy -- such as carbamazepine (Tegretol), gabapentin (Neurontin), lamotrigine (Lamictal), or others -- are occasionally used in combination with antipsychotic drugs for patients who do not respond to standard drugs.
Estrogen Replacement in Women. Estrogen may be nerve-protective. Some investigators have proposed using estrogen therapy to help with cognitive impairment. However, evidence is weak, and cancer and cardiovascular risks of estrogen therapy must be considered.
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