Home Clinical Trials Tardive Dyskinesia (A Rare Disorder) – Pathophysiology, Etiology and Complications

Tardive Dyskinesia (A Rare Disorder) – Pathophysiology, Etiology and Complications

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Tardive dyskinesia (TD) is an involuntary neurological movement disorder caused by the use of dopamine receptor blocking drugs that are prescribed to treat certain psychiatric or gastrointestinal conditions. Long-term use of these drugs may produce biochemical abnormalities in the area of the brain known as the striatum. The reasons that some people who take these drugs may get tardive dyskinesia, and some people do not, is unknown. Tardive dystonia is a more severe form of tardive dyskinesia in which slower twisting movements of the neck and trunk muscles are prominent.

Synonyms of Tardive Dyskinesia

  • linguofacial dyskinesia
  • oral-facial dyskinesia
  • tardive dystonia
  • tardive oral dyskinesia
  • TD
  • tardive stereotypy

Tardive dyskinesia is caused by long-term use of a class of drugs known as neuroleptics. Neuroleptic drugs are often prescribed for management of certain mental, neurological, or gastrointestinal disorders. Metoclopramide and prochlorperazine are drugs used for chronic gastrointestinal conditions that may cause tardive dyskinesia. Neuroleptic drugs block dopamine receptors in the brain. Dopamine is a neurotransmitter which is a chemical that helps brain cells to communicate. Although most cases occur after a person has taken these drugs for several years, some cases may occur with shorter use of neuroleptic drugs.

Tardive dyskinesia affects individuals who have been taking neuroleptic drugs for a long period of time. A high percentage of schizophrenic people who have spent long periods of time taking these drugs have a high risk of developing TD. However, neuroleptic drugs are also prescribed for depression, some digestive disorders, and other neurologic illnesses.

Some key statistics:

  • The cumulative incidence is about 4% to 5% annually; the prevalence rate is 20% to 30%.
  • Younger patients are at risk and may be particularly susceptible to more generalized and dystonic movements, but older age is a major risk factor.
  • The annual incidence in patients older than 45 years is 15% to 30% after 1 year of treatment; the prevalence rate is about 50% to 60%.
  • Tardive dyskinesia has been linked with female gender, race, higher ratings of negative symptoms and thought disorder, greater cognitive impairments, acute drug-induced movement disorders, substance abuse, and diabetes.
  • Older adults and patients with schizophrenia may be at greatest risk, but patients with mood disorders are at risk and have been considered to be at high risk.
  • Regardless of diagnosis, tardive dyskinesia is not rare and anyone exposed to treatment with antipsychotics is at risk.

First- vs second-generation antipsychotics

  • A 6- to 12-fold reduction in tardive dyskinesia risk was found with newer second-generation antipsychotics (SGAs) compared with haloperidol.
  • The relative risk of tardive dyskinesia with SGAs is significantly less on average than that with older first-generation antipsychotics. The risk associated with clozapine is probably least.
  • The SGAs retain some risk. No currently available antipsychotic is risk-free.
  • Additional risk factors for the development and persistence of tardive dyskinesia are longer duration of antipsychotic treatment and greater cumulative drug doses.

Diagnosis

A diagnosis of tardive dyskinesia is typically made in people who have taken neuroleptic medications for at least three months, have signs and symptoms that are suggestive of the condition, and have undergone testing to rule out other conditions that cause similar features. This testing may include specialized laboratory tests and imaging studies such as computed tomography (CT scan), magnetic resonance imaging (MRI scan), positron emission tomography (PET scan) and single-photon emission computerized tomography (SPECT scan).

Signs & Symptoms

Tardive dyskinesia is characterized by involuntary and abnormal movements of the jaw, lips and tongue. Typical symptoms include facial grimacing, sticking out the tongue, sucking or fish-like movements of the mouth. In some cases, the arms and/or legs may also be affected by involuntary rapid, jerking movements (chorea), or slow, writhing movements (athetosis). Symptoms of tardive dystonia include slower, twisting movements of larger muscles of the neck and trunk as well as the face.

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Standard Therapies

Treatment of tardive dyskinesia initially consists of discontinuing the neuroleptic drug as soon as involuntary facial, neck, trunk, or extremity movements are identified in people taking neuroleptic drugs if this is felt to be safe psychiatrically. Use of an “atypical” neuroleptic drug is often used in place of traditional neuroleptics if felt to be psychiatrically appropriate. However, the “atypical” neuroleptic drugs are also capable of causing or perpetuating tardive dyskinesia. In some cases, physicians may be forced to reinstitute a neuroleptic drug if the tardive dyskinesia symptoms do not disappear and become very severe after medication is discontinued.

In 2017, Ingrezza (valbenazine) was FDA approved to treat adults with tardive dyskinesia. Ingrezza is manufactured by Neurocrine Biosciences, Inc.

In 2017, Austedo (deutetrabenazine) was FDA approved for the treatment of tardive dyskinesia in adults. Austedo is manufactured by Teva Pharmaceutical Industries Ltd.

Investigational Therapies

Studies are ongoing to determine possible new drug therapies for the treatment of tardive dyskinesia. Choline, lithium, bromocriptine, baclofen, methyldopa, valproate, clonidine, propranolol, amantadine, clonazepam, and nifedipine have occasionally been helpful but in most cases do not improve dyskinesia. Tetrabenazine is often useful for symptomatic treatment of tardive dyskinesia and is currently available for use in the US. However, it carries the risk of causing or aggravating depression. Other experimental drugs are being tested to reduce or eliminate the symptoms of tardive dyskinesia.

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