First-generation antipsychotics are known for causing tardive dyskinesia (TD). These include:

  • haloperidol
  • chlorpromazine
  • fluphenazine
  • perphenazine
  • prochlorperazine
  • thioridazine
  • trifluoperazine

Second-generation antipsychotics such as risperidone, quetiapine, aripiprazole, and olanzapine may also increase the risk for TD but at a lower rate when compared to first-generation antipsychotics.

Both first- and second-generation antipsychotics affect the risk for TD development because of the way they work on the brain, which involves blocking dopamine receptors (D2 receptors) in the central nervous system.

Dopamine is a chemical in the brain that helps stimulate smooth motor movements. When the D2 receptors are blocked and there isn’t enough dopamine, movements are not smooth or controlled, causing TD.

However, when comparing first-generation antipsychotics to second-generation antipsychotics, it has been noted that first-generation antipsychotics are more likely to increase the risk for TD development because they bind more tightly to the D2 receptors and are potent D2 receptor antagonists.

Atypical antipsychotics (second generation) have a lower risk of causing TD. These medications target certain areas of the brain. Unlike first-generation antipsychotics, they are more selective and do not just latch on to the striatum (the part of the brain that causes movement), so there is a reduced chance of TD.

The second-generation antipsychotics also improve mood by blocking serotonin.

Risk factors for TD, in addition to using antipsychotic drugs, include:

  • aging
  • female sex
  • dementia
  • past brain injury
  • ancestry
  • experiencing early extrapyramidal symptoms

Additionally, previous use of first-generation antipsychotics increases TD risk. Some research found that [females] are more at risk after menopause because estrogen may act like an antioxidant and affect dopamine-related actions.

Studies have shown that people of African descent have a higher likelihood of developing TD in comparison to [people] of European descent. In contrast, people of Asian descent have a lower risk of TD than those with Caucasian ancestry.

The two most common mental health conditions associated with TD are schizophrenia and bipolar disorder, but it can be associated with other conditions, like major depressive disorder. These disorders are associated with TD because they can be treated with antipsychotics.

Evidence suggests that individuals with bipolar disorder are at the highest risk of developing TD, despite the lower doses of antipsychotic medications used for this disorder. People [taking] antidepressants are at lower risk of developing TD; however, some populations, such as older adults, are at increased risk of antidepressant-induced TD.

One factor that has been shown to make TD worse is the use of anticholinergic drugs, such as procyclidine, which are used for COPD and bladder control.

People who are [taking] lithium with another antipsychotic drug are also at risk of worsening their TD.

Studies have shown that when discontinuing or tapering the antipsychotic, there is initial worsening of TD symptoms in 33–53% of patients but improvement in symptoms over a longer period of time in 36–55% of patients. Because of this, medical professionals should use careful judgment when deciding if antipsychotics should be decreased or discontinued.

Since TD is an involuntary movement condition caused by medications that affect dopamine receptors, the first step to getting a diagnosis is evaluating medications, even if there has been a discontinuation or change in medications.

The most widely used testing tool is the Abnormal Involuntary Movement Scale (AIMS), which is recommended before starting antipsychotic medication and during follow-up visits for monitoring. To confirm a TD diagnosis, someone must continue to have symptoms for at least 1 month [after being on an antipsychotic for 3 months].

The longer you are on antipsychotic medication, the greater your risk of developing TD. A higher dose will also increase the risk for TD.

People taking antipsychotics that cause TD must be slowly tapered off the medication. The goal is to come off the medication safely and not have psychotic symptoms worsen. This is especially important if someone has been on the medication for an extended period of time.

Reducing the dosage is also key to helping alleviate TD symptoms. However, medical professionals should monitor you to see if the reduction causes the TD to worsen.

In certain cases, stopping antipsychotics may be worse for someone because it can lead to further complications. For many people who are prescribed these medications, the medications are what allow them to function on a daily basis. A healthcare provider can evaluate an alternative antipsychotic that may be better at reducing the odds of TD.

Vesicular monoamine transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, can be prescribed to treat TD while taking antipsychotic medications. This can help you continue to function on your medications and be relieved of TD symptoms.

Dr. Ifeanyi Olele is a board certified psychiatrist dedicated to supporting individuals with mental health challenges, including anxiety, depression, and ADHD. Currently, Dr. Olele is the founder and CEO of Genesis Psychiatric Solutions and Genesis TMS and Wellness. He provides a range of services, including transcranial magnetic stimulation for conditions like treatment-resistant depression and OCD. They have a presence in Alexandria, Virginia; Fairfax, Virginia; and Washington, D.C.