Considerations for Treating TD

Treating TD may facilitate more focus on the underlying mental health disorder.

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Manage for the long-term

  • Management of the underlying mental health disorder is a long-term commitment
  • TD can be chronic, disabling, and unremitting, underscoring the need for effective long-term management
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Maintain stability of the underlying mental health disorder

  • TD can complicate management of the underlying mental health disorder, as adherence to antipsychotic drugs (APDs) may decrease after TD diagnosis
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Select appropriate treatment strategy

  • TD may be treated without changing the APD dose
  • APD dose reduction may not improve symptoms, as TD is typically persistent
  • Anticholinergics can worsen TD
  • Vesicular monoamine transporter 2 (VMAT2) inhibitors are approved for treatment of TD in adults

Treatment Considerations for DIP and TD

The treatment approach for either movement disorder includes the following steps:

REVIEW the patient’s current APD therapy and dose, while maintaining the stability of the underlying mental health disorder.

Considerations
for DIP

DIP may improve or resolve with a reduction or discontinuation of the APD or by switching to one with a lower D2 binding capacity. These changes should take into consideration the stability of the patient’s underlying mental health condition.

Considerations
for TD

When managing a patient with an underlying mental health disorder, along with the need to stabilize and maintain the patient's mental health, the implications of TD should be considered.

Dose reduction or discontinuation of an APD may not be feasible.

CONSIDER TREATMENT with an appropriate therapeutic agent for the movement disorder. It is essential to differentiate TD from DIP because the treatment for one disorder may worsen the other.

Treatment Options
for DIP

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Anticholinergics are indicated for the treatment of DIP

  • Note that while anticholinergics may improve DIP, they should be used with caution because they
    • Can worsen TD
    • Are associated with side effects (eg, constipation, confusion, dry mouth, delirium) and cognitive decline
    • Are not appropriate for many older adults (Beers Criteria)

Treatment Options
for TD

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The American Psychiatric Association (APA) Practice Guideline recommends a VMAT2 inhibitor as first-line treatment for adults with TD regardless of TD severity, without the requirement to modify the APD dose

  • The APA recommends that patients who have moderate to severe or disabling TD associated with antipsychotic therapy be treated with a reversible inhibitor of VMAT2
  • APA guidelines recommend considering a VMAT2 inhibitor to address TD-associated impairments and impact on social functioning
  • Note that while VMAT2 inhibitors may improve TD, they may worsen parkinsonism

MANAGE the movement disorder and the underlying mental health disorder over the long-term.

Considerations
for DIP

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SHORTEST TIME NECESSARY

Although anticholinergics are indicated for the treatment of DIP, it is important to consider their potential short- and long-term adverse effects.

According to the APA Practice Guideline, “If an anticholinergic medication is used, it is important to adjust the medication to the lowest dose that is able to treat the parkinsonian symptoms. In addition, it is also important to use the medication for the shortest time necessary.”

Considerations
for TD

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LONG-TERM MANAGEMENT

For many patients, TD is chronic, disabling, and unremitting, which underscores the need for effective long-term management.

DIP and TD Are Different; So Are Their Treatments

APD discontinuation

Anticholinergics

VMAT2 inhibitors

DIP

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May improve DIP

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Indicated for DIP

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May worsen DIP

APD discontinuation

Anticholinergics

VMAT2 inhibitors

TD

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Not likely to improve TD

Purple X inside a purple circle.

May worsen TD

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Indicated for TD

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PerfecTD:

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Question 1 of  

For each statement, click whether DIP or TD is being described.

Anticholinergics are indicated for treatment of this disorder.

 
 
 

Answer: DIP

Anticholinergic medications are indicated for DIP. Importantly, the prescribing information for benztropine
mesylate, a commonly used anticholinergic, includes a warning that the drug may exacerbate symptoms of TD.

For each statement, click whether DIP or TD is being described.

Anticholinergic medication may worsen symptoms associated with this disorder.

 
 
 

Answer: TD

Anticholinergic medications can worsen the symptoms associated with TD. In fact, the prescribing information for benztropine mesylate, a commonly used anticholinergic, includes a warning that the drug may exacerbate symptoms of TD.

For each statement, click whether DIP or TD is being described.

VMAT2 inhibitors are indicated for treatment of this disorder.

 
 
 

Answer: TD

VMAT2 inhibitors are indicated for the treatment of TD in adults. In fact, the APA recommends that TD symptoms that have an impact on the patient, regardless of severity, should be managed with a VMAT2 inhibitor.

Thank you for completing

DIP vs TD: Chapter 4

Treatment

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Summary:

Differentiating between DIP and TD is essential because they
require opposite management strategies.

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Hear From the Expert

Visit the overview page to access a short video of Dr Leslie Citrome discussing the importance of differentiating TD from DIP.

Watch

Chapter 4 References:

American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Association; 2021.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, Text Revision. Washington, DC: American Psychiatric Association; 2022.

Ascher-Svanum H et al. J Clin Psychiatry. 2008;69(10):1580-1588.

Caroff SN et al. J Clin Psychiatry. 2011;72(3):295-303.

Cloud LJ et al. Neurotherapeutics. 2014;11(1):166-176.

Cogentin® (benztropine mesylate tablets) Prescribing Information. Lake Forest, IL: Oak Pharmaceuticals, Inc; 2016.

Jain R et al. Poster presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX.

Waln O, Jankovic J. Tremor Other Hyperkinet Mov (N Y). 2013;3:tre-03-161-4138-1.

Ward KM, Citrome L. Neurol Ther. 2018;7(2):233-248.

Zutshi D et al. Tremor Other Hyperkinet Mov (N Y). 2014;4:266.

INDICATIONS AND USAGE

AUSTEDO XR® (deutetrabenazine) extended-release tablets and AUSTEDO® (deutetrabenazine) tablets are indicated in adults for the treatment of chorea associated with Huntington’s disease and for the treatment of tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO XR® and 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 XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.

Contraindications: AUSTEDO XR and AUSTEDO are contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO XR and AUSTEDO are 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 or valbenazine.

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

QTc Prolongation: AUSTEDO XR and AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO XR or AUSTEDO is administered within the recommended dosage range. AUSTEDO XR and 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 XR and AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.

Akathisia, Agitation, and Restlessness: AUSTEDO XR and 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 XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism: AUSTEDO XR and 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 XR or 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 XR and 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 XR or 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 XR and 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. Adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets.

Please see accompanying full Prescribing Information, including Boxed Warning.