Neuroleptics - Tardive Dyskinesia Causes

Also known as antipsychotic medications, neuroleptics are medications used in the treatment of mental illness - primarily schizophrenia. Some neuroleptics have also been used to treat certain digestive disorders associated with diabetes and full or partial stomach paralysis (gastroparesis). They operate by blocking receptors in the dopamine pathway of the brain that controls voluntary muscles and certain emotional response mechanisms (known as the nigrostriatal pathway).

The problems with these drugs is that while they were designed to target specific dopamine receptors, there is some "spillover" which effects muscle control and results in the symptoms associated with tardive dyskinesia and other movement disorders.

Varieties

Many different neuroleptic medications have been developed over the past sixty years or so, but all of these fall into one of three broad categories:

"Typical": these are the earliest neuroleptic drugs, dating from the early 1950s and most strongly associated with the development of tardive dyskinesia symptoms. Some of these have been phased out; others are still commonly prescribed. They are also identified as "first generation."
"Atypical": the "second generation" of neuroleptics were developed between the early 1960s and the 1980s. Although these drugs are also known to cause symptoms of tardive dyskinesia, such symptoms may take longer to develop.
"Third Generation": these medications are the latest ones to have been made available. These also have side effects that include dyskinesia, though these may be less than in older medications. Since these are the newest medications available (developed since 2001), they are also the most costly and are not likely to be prescribed under a profit-driven, privatized health care system unless the patient has the ability to pay.

Under these broad classifications are several sub-categories, each of which is represented by several different proprietary and generic varieties of medication.

First Generation Neuroleptics

There are three classifications of first-generation "typical" neuroleptic medications:

Butyrophenones: part of the ketone or alkanone group of compounds, the most common neuroleptics of this type are:
- Halperidol: this was developed by a Belgian company in the late 1950s and has been sold in the U.S. by McNeil laboratories under the brand name Haldol since 1967; a very powerful drug that is also used to control behavioral disorders as well as some of the side effects of cancer chemotherapy.
- Droperidol: another product from the same Belgian company, this drug - sold in the U.S. as Dropleptan. The FDA has required packages to carry a "black box warning" since 2001.
Phenothiazines: there are over a dozen commonly-prescribed neuroleptic drugs in this category. Those used the most by psychiatrists and physicians are:
- Chlorpromazine: marketed in the U.S. as Thorazine, this was the first antipsychotic �drug ever used for the treatment of schizophrenia, first introduced in 1950. This drug operates on several different nervous system receptors; although it has largely been replaced by second-generation medications in humans, chlorpromazine is still used by veterinarians for the treatment of domestic animals.
- Fluphenazine: better known as Prolixin, this has a potency that is an average of 60 times that of chlorpromazine. It is primarily used as an injection, administered twice a month to mental patients who refuse to take their regular medications; in certain countries, this can be imposed upon a patient against their will.
- Trifluoperazine: this drug has been used to treat a range of psychological issues as well as to control nausea and vomiting; research has indicated that it may help patients with heroin or morphine addiction. Its use is limited; symptoms of tardive dyskinesia appear in up to 4% of all patients for whom this has been prescribed in addition to akathisia and neuroleptic malignant syndrome.
- Promethazine: this was originally developed for use as a treatment for psychosis; at only 10% of the strength of chlorpromazine, it is currently prescribed as a sedative or to control nausea. It is also an ingredient in certain cough medicines and antihistamines.
Thioxanthenes: this class of first-generation neuroleptics are related to the previous one; they differ only slightly in their chemical makeup.
- Chlorprothixene: a mild antipsychotic drug only about half as potent as chlorpromazine. First introduced in 1959, it has been used in the treatment of bipolar disorders as well as psychoses.
- Flupenthixol: as the name suggests, this drug contains fluorine, a component of dental fluoride and used in antidepressants. Marketed under the trade names Dexipol and Fluxanol, it targets specific dopamine receptors as well as serotonin, which is involved in digestive function. It is known to cause akathisia, parkinsonism and other dyskinetic symptoms, but to a lesser degree than similar medications.
- Zulcopenthixol: this drug is sold by Lundbeck, Inc. under the brand name Acuphase. In addition to dyskinetic symptoms, Acuphase has also been implicated in certain forms of cancer as well as neuroleptic malignant syndrome.

Second Generation Neuroleptics

There are over a dozen atypical neuroleptics that unlike most first generation medications, are chemically unrelated to one another. They differ from the older drugs in that their mechanism is different. Originally, they were called "atypical" because it appeared as though the propensity to cause dyskinetic symptoms in some patients was absent. It is now known that atypical neuroleptics do in fact cause tardive dyskinesia and other movement disorders, though the effects take longer to manifest and may not be as severe. However, many of them have other serious side effects, such as agranulocytosis, a type of auto-immune disease in which the number of infection-fighting white blood cells are decimated.

Other side effects of atypical neuroleptics may include diabetes and inflammation of the pancreas as well as weight gain in some patients.

Common second-generation neuroleptics include:

Clozapine (Clozaril): the first atypical medication, introduced in 1959 and now implicated in agranulocytosis as well as heart inflammation.
Olanzepine (Zyprexa): a daily treatment for bipolar disorder.
Risperidone (Risperidal): a drug used "off-label" for Tourette's Syndrome and anxiety disorder.
Quetiapine (Seroquel): in addition to bipolar disorder and schizophrenia, this drug is also prescribed as a sedative.
Ziprasidone (Geodon): one of the most recent atypical neuroleptics to be approved by the FDA, it can affect heart rhythm and should be avoided by patients with cardio-vascular disease.
Paliperidone (Invega): a derivative of risperidone.

Third Generation Neuroleptics

Aripiprazole is a fairly new anti-psychotic drug developed in Japan and approved for use in the U.S. by the Food and Drug Administration in 2002. Marketed by Bristol-Myers Squibb under the brand name Abilify, it is used for the treatment of bipolar disorder and clinical depression. Its side effects include a number of movement disorders that include akathisia, dyskinesia, muscle weakness, tremors and even seizures; it is also known to cause insomnia as well as drowsiness, constipation and vision problems.

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