Every year, we recognize the first full week of May as Tardive Dyskinesia Awareness Week (TDAW), to help increase awareness and education about tardive dyskinesia. This includes awareness to health care providers around the importance of regular screening for tardive dyskinesia, and effectively treating this condition. An estimated 600,000 people in the United States have tardive dyskinesia, and that number is expected to increase with the expanding use of dopamine receptor blocking agents (DRBAs) for various conditions. Experts agree that all patients who have been prescribed DRBAs should be screened for TD at every clinical encounter, regardless of the degree of risk of tardive dyskinesia.
Dopamine regulates motor movements through both the direct (go) and indirect (stop) pathways. In the direct pathway, dopamine released into the striatum binds to dopamine 1 receptors on GABA neurons. This stimulates GABA release, which ultimately leads to glutamate release in the cortex and thus enhances motor output. In the indirect pathway, dopamine released into the striatum binds to dopamine 2 receptors on GABA neurons. This inhibits GABA release, thus inhibiting the "stop" pathway and therefore also enhancing motor output.
Figure 1. Chronic blockade of dopamine 2 receptors can lead to their upregulation; the upregulated receptors may also be supersensitive to dopamine. In the indirect (stop) pathway, this can lead to so much inhibition of the "stop" signal (left) that the "go" signal (right) is overactive, leading to the hyperkinetic involuntary movements of tardive dyskinesia.
Reference:
Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 5th edition. Cambridge University Press; 2021.