Tardive dyskinesia is mainly caused by long-term use of certain medications, especially antipsychotic (neuroleptic) drugs that block dopamine in the brain. These drugs are often used for conditions like schizophrenia, bipolar disorder, and sometimes severe depression, anxiety, or nausea.
Main medication causes
The most common cause is prolonged exposure to dopamine receptor–blocking agents, especially older (first-generation) antipsychotics, but it can also occur with some newer (second-generation) antipsychotics. Other drugs that can occasionally lead to tardive dyskinesia include certain antidepressants, anti- nausea medications (like some used for gastrointestinal problems), and a few Parkinson’s medicines.
What happens in the brain
Blocking dopamine over months or years can make dopamine receptors in movement-control areas of the brain become overly sensitive (receptor “supersensitivity”), which is thought to drive the involuntary movements. Oxidative stress and possible imbalances in other brain chemicals, such as GABA, acetylcholine, and serotonin, also appear to contribute to nerve-cell damage in regions like the basal ganglia.
Risk factors
Risk is higher with longer duration and higher doses of dopamine-blocking medications, and especially with first-generation antipsychotics. Older age, female sex (particularly after menopause), Black race, diabetes, brain injury or dementia, substance or alcohol use, and coexisting movement side effects early in treatment are all associated with increased likelihood of developing tardive dyskinesia.