Tardive dyskinesia (TD) remains a challenging condition with limited reversibility, particularly after long-term exposure to dopamine receptor–blocking agents (DRBAs). Understanding risk factors, including advanced age and cumulative exposure, is essential for early intervention and informed treatment decisions.

TD first needs to be distinguished from other drug-induced movement disorders, some of which may be reversible. For example, drug-induced parkinsonism can often be reversed by stopping the antipsychotic, lowering the dose, giving something to counteract the movements, or switching antipsychotics. TD, however, is different. It develops over time due to the prolonged and more permanent effects of DRBAs on postsynaptic dopamine D2 receptors in the dorsal striatum. Over time, these blocked receptors adapt by increasing in number and function, and, once that happens, TD is very rarely reversible after prolonged exposure. There is some debate in the literature about whether TD should be considered persistent rather than permanent, as it can perhaps dissipate in some patients over time. However, I have not seen convincing data to support this. In my experience, especially in patients with schizophrenia, this has not been the case.

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Typical strategies, such as stopping or switching medications, do not really work for TD. I have encountered some cases of reversibility, such as when DRBA exposure was short and the dose was relatively low. For example, patients with major depressive disorder who were prescribed an antipsychotic as augmentation therapy on top of their antidepressant medication may fall into this category. In these cases, the exposure tends to be limited and at a lower dose. So, if TD develops in such patients, we usually try to decrease the dose of the antipsychotic and then stop it, since there are other alternatives to treat major depressive disorder. However, this does not work in some instances, with TD persisting even after discontinuing the antipsychotic medication.

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In terms of the characteristics of those who would be lucky enough to have their TD go away when stopping medication, we do not have a way to predict this. There are some genetic tests used in research to predict an individual’s susceptibility to developing TD, but it likely involves multiple genes. No test is commercially available, but maybe in the future we will be able to identify who is at high risk and proceed accordingly.

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The 2 most important risk factors that increase the chances of developing TD are advanced age and cumulative exposure to a DRBA. For example, a 60-year-old patient starting antipsychotic therapy for the first time is going to be much more at risk than someone who is 18, so we have to be more vigilant with older patients. Cumulative exposure is also a significant factor, especially if the agent has high affinity for the dopamine D2 receptor. First-generation antipsychotics such as haloperidol are especially notorious, and we generally try to avoid them, if possible.

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So, my advice is to be mindful of the TD risk factors, be vigilant, and prescribe DRBAs at the lowest possible dose. If possible, use the antipsychotic for a limited period to decrease a patient’s risk. However, that is not possible for someone with schizophrenia, for example, in whom ongoing treatment is necessary. Fortunately, we now have treatment options for TD, and, should TD emerge, there are effective and well-tolerated therapies that we can use. The bottom line is that for TD to be potentially reversible, we have to catch it early when it is still mild and get the patient off the DRBA, and then the chances of reversibility are better. However, once someone has had prolonged exposure, especially at an older age, reversibility becomes very unlikely.