Tardive dyskinesia (TD) is a neurological syndrome characterized by involuntary, repetitive body movements. The term “tardive” means delayed, indicating these movements often appear after prolonged medication use, while “dyskinesia” refers to abnormal, uncontrolled movements. TD is an iatrogenic disorder, caused by medical treatment, linked to certain medications that affect the brain’s chemical messengers. These movements manifest as grimacing, lip smacking, tongue protrusion, rapid eye blinking, or involve the limbs or torso. In some individuals, TD can interfere with daily functioning.
Primary Medications Linked to Tardive Dyskinesia
The medications most commonly associated with tardive dyskinesia are antipsychotics, also known as neuroleptics. These drugs are primarily prescribed to manage psychiatric conditions such as schizophrenia, bipolar disorder, and severe depression or anxiety. Antipsychotics work by affecting dopamine pathways in the brain, which helps alleviate symptoms of psychosis.
Both older and newer generations of antipsychotics can induce TD, though the risk varies. First-generation or “typical” antipsychotics carry a higher risk of causing TD compared to second-generation or “atypical” antipsychotics. Common examples of first-generation antipsychotics include haloperidol, chlorpromazine, fluphenazine, perphenazine, and prochlorperazine.
Newer atypical antipsychotics, such as risperidone, olanzapine, quetiapine, and aripiprazole, are associated with a lower risk of TD, though it is still present. The specific risk can depend on the individual medication and its potency.
Other Medications That Can Induce Tardive Dyskinesia
Beyond antipsychotics, other classes of medications can also lead to tardive dyskinesia, though generally with a lower incidence. Antiemetics, drugs used to prevent nausea and vomiting, are notable culprits. Metoclopramide and prochlorperazine are specific antiemetic examples strongly linked to TD, with metoclopramide carrying a boxed warning from the FDA regarding this risk.
Certain antidepressants, while less commonly associated with TD than antipsychotics, can also induce the condition, especially with long-term use in older adults. Examples include selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and tricyclic antidepressants such as amitriptyline, doxepin, and imipramine. Other medications reported to cause TD in rare cases include:
- Lithium, used for bipolar disorder.
- Certain antiseizure medications like phenytoin, carbamazepine, and lamotrigine.
- Antihistamines, specifically hydroxyzine.
- Antimalarials such as chloroquine, particularly with prolonged administration.
How Medications May Lead to Tardive Dyskinesia
The primary theory explaining how medications cause tardive dyskinesia centers on their impact on dopamine receptors in the brain. Many implicated drugs, particularly antipsychotics, work by blocking dopamine D2 receptors. Dopamine is a neurotransmitter that plays a significant role in controlling movement.
When dopamine D2 receptors are chronically blocked by these medications, the brain’s neurons may compensate by increasing the number or sensitivity of these receptors. This phenomenon, known as dopamine receptor hypersensitivity, means the receptors become overly responsive to dopamine when eventually released. The heightened sensitivity can lead to an augmented response in dopamine signaling, resulting in the involuntary movements characteristic of TD. While this D2 receptor hypersensitivity hypothesis is widely accepted, some research suggests other neurotransmitters like serotonin, acetylcholine, and GABA may also be involved, or that changes in D1 receptor function could play a role.
Factors Increasing Tardive Dyskinesia Risk
Several factors beyond the medication itself can increase an individual’s likelihood of developing tardive dyskinesia. The duration and dosage of medication are significant contributors, with longer treatment periods and higher doses correlating with an elevated risk. Older age is also a well-established risk factor, particularly for individuals over 40, and especially those over 65, due to age-related neurological changes.
Female gender, especially in post-menopausal women, is associated with a higher risk of TD. Pre-existing neurological disorders, cognitive impairment, and intellectual disability can also increase susceptibility. Certain underlying medical conditions like diabetes and substance abuse, including alcohol consumption and smoking, have been identified as additional risk factors. While these factors elevate the risk, they do not guarantee the development of TD, and the primary trigger remains the use of specific medications.