Tardive Dyskinesia

Metoclopramide & 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2000, the FDA issued warnings that Cisapride was found to cause cardiac arrhythmia in certain patient, and the drug was withdrawn from the U.S. market six months later.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.