Tardive dyskinesia (TD) is a complex syndrome with a highly variable presentation and prognosis that is influenced by patient age and sex, along with the duration of exposure to and potency of dopamine receptor–blocking agents (DRBAs). Dose reduction or drug discontinuation and the use of VMAT2 inhibitors may help alter the course of the disease and improve long-term outcomes.

TD typically occurs after exposure to DRBAs. The risk of developing TD is highest in patients taking conventional antipsychotics, around 30%. In patients taking the newer, atypical antipsychotics, there is still a risk, but that risk may be reduced to 7.2% in those without prior exposure to conventional antipsychotics. The trajectory of TD symptoms is quite variable, as some patients may experience a substantial improvement in symptoms and then those symptoms remain stable, while others may have a progressive worsening of their symptoms. The likelihood of TD symptoms going into remission seems to be influenced by multiple factors, including age and the duration of exposure to DRBAs. Fortunately, there are now several US Food and Drug Administration (FDA)–approved treatments that appear to help change the natural history of TD in some patients.

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An important aspect of the long-term treatment of a patient with TD is the need for a multidisciplinary approach and to determine if continued exposure to DRBAs is necessary or if changes can be made to some of the medications that they are taking. This requires a close collaboration between clinicians, typically between neurologists and psychiatrists. As a general principle, it makes sense to reevaluate a patient’s need for a DRBA and to consider the use of an atypical antipsychotic first. There are also other therapies that may carry a lower risk of long-term side effects. In some cases, combining therapies with complementary or selective effects may be considered. If a patient needs to remain on a DRBA, clinicians should consider using the lowest effective dose possible and frequently reevaluate their TD symptoms.

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Reducing the dose of or stopping antipsychotics may lead to some improvement in TD symptoms in some patients but can worsen TD symptoms in others. This can make it very difficult for patients to agree to discontinue their medication. And even if they do, their symptoms may persist.

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The development of VMAT2 inhibitors represents an important advancement in the treatment of patients with TD who continue to experience symptoms after the discontinuation of a DRBA. VMAT2 inhibitors deplete dopamine, which may help with symptoms. Long-term VMAT2 inhibitor therapy appears to be effective at controlling symptoms and well tolerated. Moreover, there are now data suggesting that the use of VMAT2 inhibitors has an impact on patient quality of life. However, it is important to monitor patients receiving VMAT2 inhibitors for potential side effects such as sedation, depression, and parkinsonism.