TD Management

Differential Diagnosis

Differential diagnosis is key to identifying and managing tardive dyskinesia (TD)

TD is distinct^1-4

Although the symptoms of TD and drug-induced parkinsonism (DIP) may appear similar, they are the
result of different pathophysiological mechanisms. It is therefore important to appropriately diagnose TD
and DIP because they require distinctly different therapeutic management. Treating either condition with
a therapy not specifically indicated for it could lead to a worsening of symptoms.

Appropriate management of TD requires differentiating between TD and DIP

30.0% of patients treated with typical APDs^5,6 7.2% of patients treated with atypical APDs^5,6	Prevalence	20% to 35% in patients taking APDs (typical and/ or atypical)⁷
Dopamine blockade upregulates dopamine receptors and increases dopamine signaling⁷	Mechanism	Dopamine blockade reduces dopamine signaling⁷
Delayed—occurs months or years following administration of APD therapy^6,8 Elderly persons may develop symptoms sooner^6,8	Timing of onset	Acute—occurs within days or weeks following administration of APD therapy⁷
Acute: may fail to improve or may induce withdrawal dyskinesia⁶ Chronic: may reduce chance of worsening⁶	Decrease antipsychotic dose/potency	May improve or resolve symptoms^6,7

Prevalence
TD	DIP
30.0% of patients treated with typical APDs^5,6 7.2% of patients treated with atypical APDs^5,6	20% to 35% in patients taking APDs (typical and/or atypical)⁷
Mechanism
TD	DIP
Dopamine blockade upregulates dopamine receptors and increases dopamine signaling⁷	Dopamine blockade reduces dopamine signaling⁷
Timing of onset
TD	DIP
Delayed—occurs months or years following administration of APD therapy^6,8 Elderly persons may develop symptoms sooner^6,8	Acute—occurs within days or weeks following administration of APD therapy⁷
Decrease antipsychotic dose/potency
TD	DIP
Acute: may fail to improve or may induce withdrawal dyskinesia⁶ Chronic: may reduce chance of worsening⁶	May improve or resolve symptoms^6,7

Differential Diagnosis Flashcard. Differentiate between TD and drug-induced parkinsonism.

Download the differential diagnosis flashcard for reference in your clinical practice.

LEARN MORE: EVALUATING TD SYMPTOMS

AUSTEDO^® (deutetrabenazine) tablets may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

When treating TD, consider all options available to you, including those that may not require APD adjustments⁹

While APD manipulation has historically been used, it is not always effective:

Changes in APD dosing can have a negative impact on psychiatric status⁹
Withdrawal can exacerbate TD symptoms⁶
TD symptoms often persist even after discontinuation or dose reduction⁶

Watch: Chapter 1

Considering the landscape of antipsychotic usage

Watch: Chapter 2

Opposing mechanisms of TD and DIP

Watch: Chapter 3

Differential diagnosis of TD

For more videos, visit the YouTube page for AUSTEDO.

APD, antipsychotic drug; EPS, extrapyramidal symptoms; VMAT2, vesicular monoamine transporter 2.

REFERENCES: 1. Motor systems: basal ganglia. In: Neuroanatomy. 409-421. Accessed June 9, 2022. http://www.neuroanatomy.wisc.edu/coursebook/
motor2.pdf 2. Hauser RA, Truong D. Tardive dyskinesia: out of the shadows. J Neurol Sci. 2018;389:1-3. 3. Caroff SN, Hurford I, Lybrand J, Campbell EC. Movement disorders induced by antipsychotic drugs: implications of the CATIE schizophrenia trial. Neurol Clin. 2011;29:127-148. 4. Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008;21:151-156. 5. Carbon M, Hsieh C-H, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78(3):e264-e278. 6. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013;3:tre-03-161-4138-1. doi:10.7916/D88P5Z71 7. Ward KM, Citrome L. Antipsychotic-related movement disorders: drug-induced parkinsonism vs. tardive dyskinesia—key differences in pathophysiology and clinical management. Neurol Ther. Published online July 19, 2018. doi:10.1007/s40120-018-0105-0 8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013. 9. Caroff SN, Miller DD, Dhopesh V, Campbell EC. Is there a rational management strategy for tardive dyskinesia? Curr Psychiatr. 2011;10(10):22-32.

Important safety information

Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO is contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.

Contraindications: AUSTEDO is contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO is also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine (Xenazine^®) or valbenazine (Ingrezza^®).

Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects.

QTc Prolongation: AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO is administered within the recommended dosage range. AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.

Akathisia, Agitation, and Restlessness: AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism: AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.

Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO.

Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects.

Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntington’s disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia.

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Differential diagnosis is key to identifying and managing tardive dyskinesia (TD)

TD is distinct1-4

TD

DIP

Prevalence

Mechanism

Timing of onset

Decrease antipsychotic dose/potency

Prevalence

Mechanism

Timing of onset

Decrease antipsychotic dose/potency

View Demystifying EPS: TD Is Distinct—a 3-part series on the importance of differential diagnosis

TD is distinct^1-4