One of the greatest challenges that we have in the management of drug-induced movement disorders is distinguishing between TD and drug-induced parkinsonism. Clearly, these are distinct entities, and they are treated differently; thus, it is imperative to distinguish between the 2 disorders. Both are associated with antipsychotic medications, and both occur at higher rates among older individuals. 

The 2022 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision now spells out that treatment for one condition may worsen the other. The availability of the vesicular monoamine transporter 2 (VMAT2) inhibitors for the treatment of TD is also noted. VMAT2 inhibitors are very different from anticholinergics. Benztropine, which is an anticholinergic that is commonly used to treat drug-induced parkinsonism, may worsen TD and contribute to memory impairment, so benztropine would be inappropriate for a patient with TD. In contrast, 2 VMAT2 inhibitors have been developed and approved by the US Food and Drug Administration for the treatment of TD (ie, valbenazine and deutetrabenazine), but VMAT2 inhibitor therapy given to someone who has drug-induced parkinsonism could actually make the condition worse.

We have the understanding that drug-induced parkinsonism is reversible and avoidable, whereas TD can be irreversible and is sometimes unavoidable. I often favor addressing the drug-induced parkinsonism first, because it is relatively straightforward. One can judiciously select an antipsychotic from the start, avoiding the use of first-generation antipsychotics, and then manage the dose appropriately. A fairly rapid improvement in parkinsonian symptoms can be observed after a dose reduction of an antipsychotic, whereas a dose reduction can lead to a temporary exacerbation of symptoms in TD. Increasing the dose of an antipsychotic medication can mask the TD, at least temporarily. 

One of the first steps in the management of TD should be to gradually discontinue any anticholinergic medications, as they may worsen the patient’s current TD symptoms. VMAT2 inhibitors should be used in situations in which the antipsychotic dose is stable and during the maintenance phase of antipsychotic treatment (ie, when we are not interfering with the TD by changing dose of the antipsychotic treatment). That is the time to use a VMAT2 inhibitor and be confident about its treatment effect.

Hypothetically, if an anticholinergic such as benztropine were given to a patient who is believed to have drug-induced parkinsonism and the movement disorder worsens, the diagnosis should be revisited, as it is likely that the patient actually has TD rather than drug-induced parkinsonism. In the same patient, if benztropine does not lead to improvements, the dose can be reduced gradually and then discontinued to see if movements decrease. Similarly, if a VMAT2 inhibitor is administered but seems to worsen the patient’s movements, the diagnosis of TD should be revisited, as it is likely that the patient actually has drug-induced parkinsonism and not TD and should be treated accordingly.