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What causes tardive dyskinesia?

Learn how neuroleptic medications can cause this involuntary movement disorder.

Pills spilling out of prescription bottles on a table.

Updated on November 15, 2023

Tardive dyskinesia, sometimes shortened as TD, is a disorder that occurs as a result of taking antipsychotic medications. It is also sometimes caused by medications used to treat neurological and gastrointestinal (GI) disorders.

When a person has TD, they experience involuntary muscle movements. These movements are described as repetitive and jerky, and they can affect both the face and the rest of the body—for example, repeated blinking of the eyelids, fish-like movements of the mouth, or moving the fingers as if typing. Tardive translates to “delayed” and dyskinesia translates to “abnormal movement.”

Neuroleptic medications

TD is a side effect of drugs called neuroleptic medications. Also called antipsychotic medications, neuroleptic medications are used to treat a variety of psychiatric disorders, most commonly schizophrenia, but also other conditions, including depression, manic episodes, and some rare neurological disorders.

First- and second-generation

While the exact cause of schizophrenia is unknown, the disorder is associated with abnormalities in neurotransmitters. Neurotransmitters are chemical messengers that help brain cells interact with other brain cells. Some examples include dopamine, serotonin, and epinephrine (also known as adrenaline). Neurotransmitter abnormalities are also associated with depression, bipolar disorder, and Parkinson’s disease.

Neuroleptic drugs work by altering the function of neurotransmitters. There are two broad categories:

  • First-generation neuroleptic medications, which act on dopamine receptors.
  • Second-generation neuroleptic medications, which act on dopamine receptors as well as serotonin receptors. While second-generation neuroleptics act on dopamine receptors, they have a difference mechanism of action than the first-generation drugs.

As you can probably guess from the category names, first-generation neuroleptic medications are older and second-generation neuroleptics are newer. First-generation neuroleptics were introduced in the 1950s and are still in use today. Second-generation refers to neuropeptic drugs that became available starting in the 1980s. By the early 2000s, the vast majority of neuroleptic drugs that were prescribed were second-generation. Generally, second-generation neuroleptics are associated with fewer side effects.

Treatment

Because people with TD often depend on the medication that is causing TD, the disorder can be difficult to treat. Treatment may involve discontinuing the current medication and switching to another, which must be done with caution and always under the guidance of a qualified healthcare provider. Symptoms of TD can become worse when a medication is discontinued, and symptoms may persist when a person switches to a different neuroleptic medication.

There are two drugs that are approved by the FDA for the treatment of TD. Both drugs are vesicular monoamine transporter 2 (VMAT2) inhibitors, which work by regulating chemical signaling in the brain, which helps reduce the nerve signaling that causes involuntary movement. VMAT2 inhibitors are also used to treat other involuntary movement disorders.

Article sources open article sources

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J.P. Kesby, D.W. Eyles, J.J. McGrath and J.G. Scott. Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience. Translational Psychiatry, 2018. Vol. 8, No. 30.
Ralf Brisch, Arthur Saniotis, et al. The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue. Frontiers in Psychiatry, 2014. Vol. 5, No. 47.
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