Researchers of a study examined the effectiveness of vesicular monoamine transporter-2 (VMAT2) inhibitors and other agents in light of different theories regarding the development of tardive dyskinesia (TD). Researchers found that, while VMAT2 inhibitors offer an effective treatment to reduce the severity and impact of TD, other treatment options that were previously limited by methodological constraints warrant reevaluation in adequately powered trials. Targeted treatments for patients who do not respond to or cannot tolerate VMAT2 inhibitors, as well as for different subtypes of TD, are also important to develop.
Dopamine D2-receptor blockade is the trigger for TD, but the potential irreversibility of the condition appears to arise from selective damage to striatal interneurons, potentially involving mechanisms such as glutamate, acetylcholine, GABA, or oxidative stress. This suggests the presence of multiple therapeutic targets that could be explored to prevent irreversible changes and improve TD prevention and treatment. Research focusing on non-dopaminergic interventions and multi-circuit nodal points in the basal ganglia may prove fruitful in the future.
Reference: Caroff SN. Recent Advances in the Pharmacology of Tardive Dyskinesia. Clin Psychopharmacol Neurosci. 2020;18(4):493-506. doi: 10.9758/cpn.2020.18.4.493.