Tardive dyskinesia

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.

Symptoms

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.

Causes

Tardive dyskinesia is a serious side effect that occurs when you take medications called neuroleptics. Most often, it occurs when you take the medication for many months or years. In some cases, it occurs after you take them for as little as 6 weeks.

The drugs that most commonly cause this disorder are older antipsychotic drugs, including:

  • Chlorpromazine
  • Fluphenazine
  • Haloperidol
  • Trifluoperazine

Other drugs, similar to these antipsychotic drugs, that can cause tardive dyskinesia include:

  • Flunarizine
  • Metoclopramide
  • Prochlorperazine

Newer antipsychotic drugs seem less likely to cause tardive dyskinesia, but they are not entirely without risk.

Prevention

Primary prevention of tardive dyskinesia is achieved by using the lowest effective dose of a neuroleptic for the shortest time. However, with diseases of chronic psychosis such as schizophrenia, this strategy must be balanced with the fact that increased dosages of neuroleptics are more beneficial in preventing recurrence of psychosis. If tardive dyskinesia is diagnosed, the causative drug should be discontinued. Tardive dyskinesia may persist after withdrawal of the drug for months, years or even permanently. Some studies suggest that physicians should consider using atypical antipsychotics as a substitute to typical antipsychotics for patients requiring medication. These agents are associated with fewer neuromotor side effects and a lower risk of developing tardive dyskinesia.

Recent studies have tested the use of melatonin, high dosage vitamins, and different antioxidants in concurrence with antipsychotic drugs (often used to treat schizophrenia) as a way of preventing and treating tardive dyskinesia. Although further research is needed, studies reported a much lower percentage of individuals developing tardive dyskinesia than the current prevalence rate for those taking antipsychotic drugs.

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.

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.

Prognosis

If diagnosed early, the condition may be reversed by stopping the drug that caused the symptoms. Even if the drug is stopped, the involuntary movements may become permanent, and in some cases, may become worse.

Treatment

Currently, there are no FDA approved drugs for treating tardive dyskinesia, though some have shown efficacy in studies. Tetrabenazine, which is a dopamine depleting drug, is sometimes used to treat tardive dyskinesia and other movement disorders. However, it is only approved to treat chorea associated with Huntington's disease. The related VMAT2 inhibitor, reserpine, has also been tried in one small randomised double-blind placebo-controlled trial as a treatment for TD with success, as has α-methyldopa. Ondansetron (Zofran) has shown some benefit in experimental studies on tardive dyskinesia and a variety of anti-Parkinsonian medications are used such as donepezil, baclofen, and pramipexole. Clonidine may also be useful in the treatment of TD, although dose-limiting hypotension and sedation may hinder its usage. Botox injections are used for minor focal dystonia, but not in more advanced tardive dyskinesia. Benzodiazepines are an effective treatment for TD, however their use is limited by the development of tolerance which requires ever increasing doses of the benzodiazepines to be used to attenuate TD symptoms. The most popular benzodiazepine for the treatment of TD is clonazepam. Vitamin B6 has been reported to be an effective treatment for TD in two randomised double-blind placebo-controlled trials. In males, the branched-chain amino acid formula Tarvil, containing the amino acids valine, isoleucine, and leucine in a 3:3:4 ratio was reported as beneficial for motor symptoms in a small, non-blinded study.