The Facts on Tardive Dyskinesia

You’ve probably noticed from your own clinical experience that most patients taking antipsychotic medications for years do not develop TD and the same medication regimen can cause different types and severity of TD.

Does it mean there is genetic susceptibility for TD? Multiple gene candidates were recently found in association with TD, including genes coding for dopamine and serotonin receptors, antioxidative enzymes, and drug metabolism enzymes (Teo JT et al, op.cit). Therefore, although not a genetic disorder, TD might have a genetic predisposition.

Management of TD

Prevention of TD is paramount. Whenever you can, avoid DRBAs and choose alternative medications or “atypical” neuroleptics with lower potential to cause TD. If you decide to use DRBAs in your patient, frequently re-assess the need to continue treatment and watch for symptoms of TD at every visit.

Take action as soon as you notice signs of TD in your patient. The most important approach in treatment of TD is the removal of an offending drug as soon as possible. Remember, the longer patients with the symptoms of TD continue taking DRBAs, the lower their chances of recovery. But do not stop a DRBA abruptly; instead, taper it off slowly to avoid worsening of TD.

Although we know that increasing the dose of a DRBA can temporarily improve the symptoms of TD, this strategy should be avoided and used only in the most severe cases when immediate control of the disabling TD symptoms is required.

The dopamine-depleting drugs, reserpine (Serpalan) and tetrabenazine (Xenazine), are the most effective medications in any TD syndromes (see the table on page 5). Both medications prevent reuptake and recycling of the monoamines (including dopamine), thereby promoting their breakdown within the synaptic cleft.

As a result, hypersensitive dopamine receptors receive reduced dopaminergic stimulation, thus improving hyperkinetic movements in the absence of dopamine-receptor blockade.

This article originally appeared in The Carlat Psychiatry Report -- an unbiased monthly covering all things psychiatry.
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Tetrabenazine is currently considered a first-line treatment option in TD if the symptoms persist after discontinuation of a DRBA. Despite this  option, the use of tetrabenazine remains off label. So far, it is FDA-approved only for Huntington’s chorea and is only available in the USA from a specialty pharmacy (see the manufacturer’s website).

This medication is usually well tolerated; however it can cause or exacerbate depression, produce daytime somnolence, akathisia and parkinsonism, especially in higher doses. Reserpine can cause the same side effects but also orthostatic hypotension and diarrhea; therefore it is used less often.

Other, less studied medications showed some symptomatic improvement in TD according to small studies and case reports. Among those medications are amantadine (Symmetrel), clonazepam (Klonopin) and other benzodiazepines, baclofen (Lioresal), valproic acid (Depakene), zolpidem (Ambien), donepezil (Aricept), lithium, antioxidants, zonisamide (Zonegran), vitamin B6 and melatonin.

Anticholinergic medication like trihexyphenidyl (Artane) and benztropine can be effective in tardive dystonia but can exacerbate other types of TD.

Botulinum toxin injections are often used for treatment of focal dyskinesia and tardive dystonia. In the most severe and refractory cases of TD, surgical treatment such as pallidotomy or deep brain stimulation can be considered.

TCPR’s Verdict:

TD can manifest as a variety of movement disorders and can be caused by medications other than first-generation antipsychotics. Early recognition of TD symptoms and discontinuation of the offending drug can improve prognosis in TD patients. Tetrabanazine is the first-line in treatment of any type of TD.

The Facts on Tardive Dyskinesia

This article originally appeared in:

The Carlat Psychiatry Report
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This article was published in print April 2014 in Volume:Issue Volume 12, Number 4.


APA Reference
Waln,, O. (2015). The Facts on Tardive Dyskinesia. Psych Central. Retrieved on February 16, 2020, from


Scientifically Reviewed
Last updated: 8 Jul 2015
Last reviewed: By John M. Grohol, Psy.D. on 8 Jul 2015
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