Reglan & Tardive Dyskinesia
Those who have ever suffered from a condition known as gastroparesis - literally, a partial paralysis of the stomach, which prevents food from moving through the digestive tract - may have been treated with a drug called metoclopramide. This drug has been available in generic form since 1982, and is sold in the U.S. under the brand names Maxolon and Reglan (among others). This drug has also been used to treat heartburn and acid reflux as well as nausea and vomiting (including those associated with cancer treatments), and has been prescribed for women to stimulate lactation or to treat migraine headaches.
Metoclopramide is a dopamine receptor antagonist. This means it essentially inhibits the delivery of electro-chemical messages from the brain to certain parts of the body (dopamine is the chemical that carries these messages, and the receptors are those parts of cells that act as receivers). Although its use as an anti-psychotic or neuroleptic drug has been limited, the mechanism is the same; as a result, this medication has been implicated in various movement disorders, including parkinsonism and tardive dyskinesia.
Brief History
Metoclopramide was first developed in Europe in the mid-1960s. As mentioned earlier, it is a dopamine antagonist, or inhibitor; like the anti-psychotic drugs implicated in tardive dyskinesia, it operates on the specific dopamine receptor identified as D2, which controls specific muscle functions as well as certain feed-back mechanisms.
Prior to 2000, patients suffering from acid reflux disease and gastroparesis were treated with a drug known as Cisapride. Like several other drugs implicated in tardive dyskinesia and other movement disorders, Cisapride was the invention of the Belgian pharmaceutical company Janssen Pharmaceutica (a division of Johnson & Johnson), which marketed it in the U.S. under the trade name Propulsid. Since 1982, the drug has been available in generic form, and is In January 2000, the FDA issued warnings that Cisapride was found to cause cardiac arrhythmia in certain patient, and the drug was withdrawn from the U.S. market six months later. It is still used by veterinarians for the treatment of hairballs in house cats, however.
Among human patients, metoclopramide - an older medication that was considered "safer" than Cisapride - made a comeback after several years of having taken a backseat to the latter.
Metoclopramide and Dyskinesia
In 2004, a research team that included medical scientists from the FDA and the Veteran's Administration published their study that came up with the following conclusion:
"Well-described TD risk factors were common in metoclopramide- associated TD reports. Given the Cisapride market withdrawal and associated increased metoclopramide utilization, the incidence of TD may increase accordingly. TD risk factors relative to the intended benefit and duration of use should be considered in metoclopramide prescribing."
This study found that patients treated with metoclopramide at greatest risk for developing symptoms of tardive dyskinesia were older women who had been on the drug for an extended period of time (although it was also noted that women made up 67 percent of patients for whom the drug was prescribed). Additional risk factors included:
Diabetes
"Organic" brain dysfunction/atrophy
Psychosis
Substance abuse
Genetic predisposition
It was not until 2009 that warnings were widely circulated.
Metoclopramide Today
Because of the disproportionate influence pharmaceutical corporations have on government agencies, it is unlikely that metoclopramide will be withdrawn from the market. Currently, 23 drug companies continue to manufacture and market metoclopramide, and two million Americans are still prescribed this drug for various digestive disorders. However, the FDA has ordered manufacturers to include a "black box" warning with the medication's packaging.
Thursday, April 28, 2016
Tardive Dyskinesia Diagnosis
The movement disorder known as tardive dyskinesia is actually a collection of symptoms that can mimic other types of disorders such as conditions related to the side effects of antipsychotic (neuroleptic) medications and congenital disorders. Accurate diagnosis can be challenging as there is no single test for tardive dyskinesia. The diagnostic process may involve more than one physician and requires the review of a thorough medical history, a physical examination and a neuro-psychological evaluation in order to determine whether one is indeed suffering from tardive dyskinesia or a different neurological disorder. The diagnostic process is complicated further by the fact that tardive dyskinesia symptoms can come and go, or may be more apparent at some times than at others. An accurate diagnosis may require several office visits.
Tardive Dyskinesia Symptoms and Related Disorders
Those with tardive dyskinesia engage in repetitive, involuntary movements without purpose. These may consist of any or all of the following:
Movement of the lips and tongue (grimacing, smacking, pursing, sticking out the tongue)
Rapid blinking
Impaired finger movement or "fluttering"
Rapid movements of the arms
Toe tapping, moving the leg up and down
Twisting and bending of the torso (in extreme cases)
There are also other similar, but unrelated movement disorders which are sometimes mistaken for tardive dyskinesia:
Dystonia: Dystonia is characterized by sustained muscular contractions which can result in the entire body twisting into abnormal and sometimes painful positions. It is usually congenital, but can occur as a result of injury, a bacterial infection, lead poisoning or drug side-effects. However, while most types of dystonia may pass, the tardive variety is usually irreversible.
Akathisia: This particular condition manifests itself as a compulsive need to move about, driven by inner feelings of anxiety or even terror. This is sometimes related to symptoms of Parkinson's disease, but is most often caused by drugs that block dopamine receptors (dopamine being the neurotransmitter that carries instructions from the brain over the nervous system). Unfortunately, this condition is often misdiagnosed as a psychological problem, leading to the prescription of yet more drugs, thus exacerbating the problem.
Tourettism: This is similar to Tourette's Syndrome, a set of tic disorders that range from facial jerks and spasms to sudden uncontrollable exclamations. In most cases, the only way to determine if such symptoms are indeed true Tourette's syndrome or related to tardive dyskinesia is to obtain a thorough medical examination and review of psychiatric history.
Myoclonus: Myoclonus is exceedingly rare, consisting of involuntary muscle twitching. It is actually a symptom of several neurological disorders, including multiple sclerosis, Parkinson's disease, Alzheimer's, epilepsy and tardive dyskinesia.
According to Dr. John Kane, writing for the American Psychiatric Association, these diseases can be distinguished from tardive dyskinesia by their outward appearance plus the muscle groups involved. True tardive dyskinesia is characterized by slow movements of the orofacial muscles, limbs and digits. Occasionally tremors may occur, but rapid, jerky, spasmodic movements are absent.
Diagnostic Process
Following a complete physical exam and neuropsychiatric evaluation, the physician may wish to run several tests to rule out pathogens, environmental toxins or genetics. The doctor may order a blood cell count and well as screening for serum electrolytes (ions that regulate various bodily functions) and copper and ceruloplasmin (the protein that carries copper in the bloodstream, enabling the metabolism of iron). The thyroid may be tested as well as connective tissues, and the patient may undergo medical imaging tests (MRI or CAT scans) of the head in order to rule out the presence of a tumor.
In the next step of the diagnosic process, the physician will attempt to elicit tardive dyskinesia symptoms by having a conversation with the patient, or providing distractions that tend to bring out such symptoms. During this process, the doctor will make careful notes of what parts of the patient's body show signs of tardive dyskinesia. Sometimes, the results will not be conclusive, and will require another examination in order to confirm the symptoms.
The movement disorder known as tardive dyskinesia is actually a collection of symptoms that can mimic other types of disorders such as conditions related to the side effects of antipsychotic (neuroleptic) medications and congenital disorders. Accurate diagnosis can be challenging as there is no single test for tardive dyskinesia. The diagnostic process may involve more than one physician and requires the review of a thorough medical history, a physical examination and a neuro-psychological evaluation in order to determine whether one is indeed suffering from tardive dyskinesia or a different neurological disorder. The diagnostic process is complicated further by the fact that tardive dyskinesia symptoms can come and go, or may be more apparent at some times than at others. An accurate diagnosis may require several office visits.
Tardive Dyskinesia Symptoms and Related Disorders
Those with tardive dyskinesia engage in repetitive, involuntary movements without purpose. These may consist of any or all of the following:
Movement of the lips and tongue (grimacing, smacking, pursing, sticking out the tongue)
Rapid blinking
Impaired finger movement or "fluttering"
Rapid movements of the arms
Toe tapping, moving the leg up and down
Twisting and bending of the torso (in extreme cases)
There are also other similar, but unrelated movement disorders which are sometimes mistaken for tardive dyskinesia:
Dystonia: Dystonia is characterized by sustained muscular contractions which can result in the entire body twisting into abnormal and sometimes painful positions. It is usually congenital, but can occur as a result of injury, a bacterial infection, lead poisoning or drug side-effects. However, while most types of dystonia may pass, the tardive variety is usually irreversible.
Akathisia: This particular condition manifests itself as a compulsive need to move about, driven by inner feelings of anxiety or even terror. This is sometimes related to symptoms of Parkinson's disease, but is most often caused by drugs that block dopamine receptors (dopamine being the neurotransmitter that carries instructions from the brain over the nervous system). Unfortunately, this condition is often misdiagnosed as a psychological problem, leading to the prescription of yet more drugs, thus exacerbating the problem.
Tourettism: This is similar to Tourette's Syndrome, a set of tic disorders that range from facial jerks and spasms to sudden uncontrollable exclamations. In most cases, the only way to determine if such symptoms are indeed true Tourette's syndrome or related to tardive dyskinesia is to obtain a thorough medical examination and review of psychiatric history.
Myoclonus: Myoclonus is exceedingly rare, consisting of involuntary muscle twitching. It is actually a symptom of several neurological disorders, including multiple sclerosis, Parkinson's disease, Alzheimer's, epilepsy and tardive dyskinesia.
According to Dr. John Kane, writing for the American Psychiatric Association, these diseases can be distinguished from tardive dyskinesia by their outward appearance plus the muscle groups involved. True tardive dyskinesia is characterized by slow movements of the orofacial muscles, limbs and digits. Occasionally tremors may occur, but rapid, jerky, spasmodic movements are absent.
Diagnostic Process
Following a complete physical exam and neuropsychiatric evaluation, the physician may wish to run several tests to rule out pathogens, environmental toxins or genetics. The doctor may order a blood cell count and well as screening for serum electrolytes (ions that regulate various bodily functions) and copper and ceruloplasmin (the protein that carries copper in the bloodstream, enabling the metabolism of iron). The thyroid may be tested as well as connective tissues, and the patient may undergo medical imaging tests (MRI or CAT scans) of the head in order to rule out the presence of a tumor.
In the next step of the diagnosic process, the physician will attempt to elicit tardive dyskinesia symptoms by having a conversation with the patient, or providing distractions that tend to bring out such symptoms. During this process, the doctor will make careful notes of what parts of the patient's body show signs of tardive dyskinesia. Sometimes, the results will not be conclusive, and will require another examination in order to confirm the symptoms.
Tardive Dyskinesia Symptoms
Little research has been done on the movement disorder known as tardive dyskinesia (TD), which affects approximately 20 percent of patients who have been treated for certain psychoses with medications known as dopamine antagonists. The symptoms are a side effect of medications that are ostensibly targeted at the specific dopamine receptor involved in emotion and lower cognitive function, but wind up affecting those involved in the function of voluntary muscle control.
Diagnosing Tardive Dyskinesia
Part of the difficulty in diagnosing tardive dyskinesia lies in the fact that its symptoms are similar to other types of disorders, including Tourette syndrome. In fact, one variety of tardive dyskinesia, known as tardive tourettism is so similar that only careful study of the circumstances surrounding the onset of the disease can determine which condition is actually present.
Other similar disorders include tardive dystonia, akathisia and myoclonus. The first differs from other types of dystonia (muscle spasms and uncontrollable movements in the torso) in that the tardive variety is permanent and is drug-related as opposed to being caused by genetics, injury or infection or environmental toxins.
Akathisia is more internalized and accompanied by inner anxiety. It is also more generalized, involving the entire body. Myoclonus manifests itself most often as brief, jerky contractions of a particular muscle group. However, the term actually refers to a symptom that may be the result of any number of neurological disorders. Usually, a differential diagnosis is required in order to determine what strain of tardive dyskinesia is present.
Characteristic Symptoms
Regardless of the variety of the disease, tardive dyskinesia is characterized by sudden, uncontrollable movements of voluntary muscle groups. Signs of classic tardive dyskinesia normally consist of coordinated, constant movements of the mouth, tongue, jaw, and cheeks. The patient may move their jaw laterally or up and down, as if chewing. The tongue may suddenly protrude or move about in a squirming, twisting manner. Repeated lip smacking and puffing of the cheeks may also be present. Severity of the condition is indicated by the frequency of these movements or spasms. In extreme cases, the tongue may move well over 60 times a minute.
In some cases, tardive dyskinesia patients may experience movement in the limbs and digits. Interestingly, these involuntary movements are more pronounced when the patient attempts to relax; emotional arousal or agitation causes these movements to decrease. Symptoms can disappear completely when the patient is asleep.
Risk Factors and Treatment
There is no cure for tardive dyskinesia although the condition can be managed in some cases. Those who are at great risk for developing tardive dyskinesia are those who have been treated with dopamine antagonists for four years or longer; according to a study from the Yale University School of Medicine. Risk factors can also be aggravated by the use of alcohol and tobacco. Post menopausal women are also at greater risk because of lower estrogen levels.
Tardive Dyskinesia Introduction & Overview
Tardive dyskinesia is a condition that may develop in patients who use metoclopramide, a drug sold under brand names such as Reglan in the United States. When a patient has been taking certain prescription drugs over a long period of time, often in high dosages, involuntary, repetitive tic-like movements can result, primarily in the facial muscles or (less commonly) the limbs, fingers and toes. The hips and torso may also be affected.
Dyskinesia refers to the involuntary nature of muscular movements or the difficulty in performing voluntary muscular movement. Tardive means a condition has the tendency to appear late. Symptoms of tardive dyskinesia can develop and persist long after use of the medication causing the disorder has been discontinued. Tardive dyskinesia can appear similar to other types of disorders, most notably Tourette's syndrome.
History
Tardive dyskinesia was first identified in 1964. By the early 1960s, symptoms associated with tardive dyskinesia were apparent in approximately 30 percent of psychiatric patients treated with antipsychotic medications, linking the development of the condition to these drugs. The development of tardive dyskinesia is commonly linked to metoclopramide use. The drug metoclopramide (sold today under the brand name Reglan, among others) was developed in Europe in the mid-1960s and became available for use in 1982. In early 2009, the Food and Drug Administration issued a warning about metoclopramide, informing the public of research that suggests the use of metoclopramide is the most common cause of drug-induced movement disorders. A 2004 study found that older women treated with metoclopramide were at an increased risk for developing symptoms of tardive dyskinesia.
Dopamine
Research indicates that tardive dyskinesia results from damage to the systems that use and process dopamine. Dopamine is a biochemical substance produced in numerous areas of the brain. It functions as a neurotransmitter, working with the brain to regulate movement and emotion within the body.
Dopamine is significant when it comes to pleasurable sensations. When dopamine receptors are blocked, the dopamine remains in the synapse (where nerve impulses are transmitted and received) for a longer period of time. This creates a sense of "false euphoria," which is why some narcotics are so addictive. The fact that dopamine remains in the synapses for an extended period may also hold clues to what causes the onset of tardive dyskinesia in certain patients. When neurons can no longer hold dopamine, Parkinson's disease may result.
Metoclopramide is a dopamine receptor antagonist and inhibits the delivery of electro-chemical messages from the brain to various parts of the body. The drug has been implicated in the development of several movement disorders, including tardive dyskinesia.
Other Factors
The development of tardive dyskinesia has often occurred in patients who have been treated for digestive and gastrointestinal disorders with medications such as metoclopramide (Deglan®, Maxolon® or Reglan®).
Other risk factors appear to be age (certain older patients are more likely to develop tardive dyskinesia), gender (the condition is more common in females), mental retardation, a history of substance abuse and a traumatic head injury. According to an article published in the Journal of the American Medical Association, 31 percent of all tardive dyskinesia patients are over 55 years of age and have been taking medications for three months or longer. Tardive dyskinesia is also caused by the side effects of certain psychoactive drugs such as anti-depressants, "dopamine antagonists" (drugs that block dopamine receptors, used to treat disorders of the nervous or circulatory system).
Treatment
The best treatment for tardive dyskinesia appears to be prevention, either by lowering the dosage of a medication known to cause this condition or switching the patient to a different drug. Tetrabenzine, a medication that reduces levels of dopamine, has been of some use in treating tardive dyskinesia symptoms. Many kinds of "anti-Parkinsonian" drugs such as Aricept and Miraplex appear to offer some benefit as well.
Tardive dyskinesia is a condition that may develop in patients who use metoclopramide, a drug sold under brand names such as Reglan in the United States. When a patient has been taking certain prescription drugs over a long period of time, often in high dosages, involuntary, repetitive tic-like movements can result, primarily in the facial muscles or (less commonly) the limbs, fingers and toes. The hips and torso may also be affected.
Dyskinesia refers to the involuntary nature of muscular movements or the difficulty in performing voluntary muscular movement. Tardive means a condition has the tendency to appear late. Symptoms of tardive dyskinesia can develop and persist long after use of the medication causing the disorder has been discontinued. Tardive dyskinesia can appear similar to other types of disorders, most notably Tourette's syndrome.
History
Tardive dyskinesia was first identified in 1964. By the early 1960s, symptoms associated with tardive dyskinesia were apparent in approximately 30 percent of psychiatric patients treated with antipsychotic medications, linking the development of the condition to these drugs. The development of tardive dyskinesia is commonly linked to metoclopramide use. The drug metoclopramide (sold today under the brand name Reglan, among others) was developed in Europe in the mid-1960s and became available for use in 1982. In early 2009, the Food and Drug Administration issued a warning about metoclopramide, informing the public of research that suggests the use of metoclopramide is the most common cause of drug-induced movement disorders. A 2004 study found that older women treated with metoclopramide were at an increased risk for developing symptoms of tardive dyskinesia.
Dopamine
Research indicates that tardive dyskinesia results from damage to the systems that use and process dopamine. Dopamine is a biochemical substance produced in numerous areas of the brain. It functions as a neurotransmitter, working with the brain to regulate movement and emotion within the body.
Dopamine is significant when it comes to pleasurable sensations. When dopamine receptors are blocked, the dopamine remains in the synapse (where nerve impulses are transmitted and received) for a longer period of time. This creates a sense of "false euphoria," which is why some narcotics are so addictive. The fact that dopamine remains in the synapses for an extended period may also hold clues to what causes the onset of tardive dyskinesia in certain patients. When neurons can no longer hold dopamine, Parkinson's disease may result.
Metoclopramide is a dopamine receptor antagonist and inhibits the delivery of electro-chemical messages from the brain to various parts of the body. The drug has been implicated in the development of several movement disorders, including tardive dyskinesia.
Other Factors
The development of tardive dyskinesia has often occurred in patients who have been treated for digestive and gastrointestinal disorders with medications such as metoclopramide (Deglan®, Maxolon® or Reglan®).
Other risk factors appear to be age (certain older patients are more likely to develop tardive dyskinesia), gender (the condition is more common in females), mental retardation, a history of substance abuse and a traumatic head injury. According to an article published in the Journal of the American Medical Association, 31 percent of all tardive dyskinesia patients are over 55 years of age and have been taking medications for three months or longer. Tardive dyskinesia is also caused by the side effects of certain psychoactive drugs such as anti-depressants, "dopamine antagonists" (drugs that block dopamine receptors, used to treat disorders of the nervous or circulatory system).
Treatment
The best treatment for tardive dyskinesia appears to be prevention, either by lowering the dosage of a medication known to cause this condition or switching the patient to a different drug. Tetrabenzine, a medication that reduces levels of dopamine, has been of some use in treating tardive dyskinesia symptoms. Many kinds of "anti-Parkinsonian" drugs such as Aricept and Miraplex appear to offer some benefit as well.
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