7 Ways to Treat Tardive Dyskinesia

The risk of TD starts to climb after age 50. Older adults develop TD at more than double the rate for younger adults: 7% vs. 2.6% per year on second-generation antipsychotics.^1,2 Mood disorders also raise the risk approximately two-fold.³ Other signs that your patient is vulnerable to TD include: early extrapyramidal side effects (EPS), diabetes, history of substance abuse, HIV+, brain injury, female gender, and African-American race.⁴

Duration and dose are two of the biggest risk factors for TD. Use the lowest effective dose. That is usually in the low range for bipolar and unipolar depression (eg, quetiapine 150 mg to 300 mg qhs); medium for mania and mixed states (eg, quetiapine 400 mg to 600 mg qhs, sometimes 800 mg); and higher for schizophrenia (eg, quetiapine 400 mg to-800 mg qhs, usually closer to 800 mg). If the patient already has TD, it is likely to improve with either dose-reduction or discontinuation of the antipsychotic.

TD is a delayed reaction to antipsychotics, and the risk increases with each year of exposure.4 While it may be unwise to taper off an antipsychotic in schizophrenia, it is a move worth considering when the antipsychotic is used for augmentation in a mood disorder.  After a patient recovers from bipolar disorder or depression with antipsychotic augmentation, I will attempt to wean the antipsychotic if a patient has remained well for at least 6 months. I will lower the dose slowly, every 1 to 2 weeks. This strategy worked well in a randomized-controlled trial of 159 patients in recovery from a manic episode. Those who weaned off the antipsychotic augmentation agent after 6 months did just as well as those who stayed on it for a year.⁵

Here is a common error to avoid: benztropine for TD. This anticholinergic relieves antipsychotic-induced Parkinsonism, but it worsens TD.⁴ It also causes significant cognitive problems, which can be more troublesome than muscle stiffness. Parkinsonism can resemble TD, and it is a risk factor for TD-but it is not treated in the same way.

If the antipsychotic cannot be stopped, treatment may be in order. Severe TD can be painful and stigmatizing, with impairments in eating, speaking, and even breathing. The two FDA-approved medications for TD─valbenazine (Ingrezza) and deutetrabenazine (Austedo)─have similar risks and benefits. Both are derived from tetrabenazine, a VMAT₂ inhibitor which has been used to treat TD since the early 1970s. A reasonable trial of these agents is 6 weeks after reaching the therapeutic dose. If it works, the VMAT₂ inhibitor will likely need to be continued as long as the antipsychotic is in place. Otherwise, the TD tends to return within a month of discontinuation.⁶

Clozapine has the lowest risk of TD, but the second place spot is up for debate. Most papers cite quetiapine, but this recommendation is based on theory. Quetiapine resembles clozapine in its low level of D2 occupancy and low rate of EPS-both of which are risk factors for TD. However, a recent meta-analysis of 52 head-to-head trials casts doubt on that idea. They found that quetiapine had the highest risk of TD among the second-generation antipsychotics, while the lowest risk, after clozapine, was with aripiprazole and then olanzapine.⁹ That is enough to give one pause before prescribing quetiapine for primary insomnia.

TD is insidious and easy to miss. Patients often deny it even when it’s clearly visible to others. Regular testing with the Abnormal Involuntary Movement Scale (AIMS) is the best way to catch it early, and early intervention is the best way to keep this neurotoxic side effect from turning into a permanent, refractory state.