DIP and TD are relatively common movement disorders resulting from the use of typical and atypical antipsychotic drugs (APDs).
UP TO
1/3
of patients taking APDs present with DIP or TD, and some patients may have both conditions.
Historically, the term “extrapyramidal symptoms,” or “EPS,” was used to describe all drug-induced movement disorders (DIMDs) experienced by patients taking APDs. Further contributing to the lack of distinction is the FDA’s use of the term EPS in product labels to describe DIMDs as adverse events. DIP and TD were routinely included within this umbrella diagnosis and, often, treated indiscriminately with anticholinergic therapy.
The concept of EPS is nonspecific and now seen as outdated, and the use of anticholinergics for all DIMDs has been shown to be inappropriate.
Extrapyramidal symptoms (EPS) is a term that is broad, nonspecific, and contributes to the lack of differentiation between DIP and TD. DIMDs include
“EPS” is still commonly used in psychiatry. However, replacing EPS with more specific terminology will help psychiatry healthcare professionals better serve their patients.
In the United States, TD affects approximately 785,000 patients. However, TD may be underdiagnosed and undertreated, with approximately 15% of patients receiving a formal diagnosis of TD and less than 6% of patients being treated with vesicular monoamine transporter 2 (VMAT2) inhibitors.
What does this mean for patients in the real world?
Even when diagnosed correctly, patients with TD may be inappropriately prescribed benztropine, an anticholinergic, despite the risk of exacerbation of TD symptoms.
In a survey of psychiatry HCPs,
used benztropine to treat TD, and 38% reported using benztropine to prevent TD.
In a separate analysis of patients with TD treated with benztropine,
were treated for >3 months.
Product Label for Benztropine, a Common Anticholinergic: PRECAUTIONS
Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them. Benztropine mesylate is not recommended for use in patients with tardive dyskinesia.
Expert guidelines caution against using anticholinergics to treat TD—but many mental health professionals remain unaware.
Read more about the use and overuse of anticholinergics from the DSM-5-TR and APA Practice Guideline.
DIP and TD are related, but they are different movement disorders with different symptoms and opposite management strategies. Understanding how to differentiate TD from DIP is critical because treatment for one disorder may worsen the other.
There are 4 key ways in which they are differentiated. Explore the differences by clicking below.
ACUTE ONSET
usually occurs within days or weeks following administration of APD therapy or increase in dose
DELAYED ONSET
usually occurs months or
years following administration of
APD therapy
REDUCED MOVEMENT
EXCESSIVE MOVEMENT
Anticholinergics that treat DIP can worsen symptoms of TD
VMAT2 inhibitors are indicated for
the treatment of adults with TD,
but may worsen parkinsonism
Question 1 of
True or False: Anticholinergics are not recommended for the treatment of patients with TD and may exacerbate symptoms of TD
Answer: True
It is critical to differentiate DIP from TD because treatment for 1 disorder can worsen the other. Anticholinergics used to treat DIP can worsen symptoms of TD, and VMAT2 inhibitors used to treat TD may worsen symptoms of DIP.
Thank you for completing
DIP vs TD: Chapter 1
The Challenge of Anticholinergic Overuse
Summary:
Now considered outdated, the term EPS is nonspecific and may
have contributed to a lack of differentiation of TD from DIP. It is
essential for HCPs to differentiate TD from DIP because treatment
for one disorder can worsen the others.
Chapter 1 References:
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, Text Revision. Washington, DC: American Psychiatric Association; 2022.
Carbon M et al. J Clin Psychiatry. 2017;78(3):e264-e278.
Caroff SN. Neuropsychiatr Dis Treat. 2019;15:785-794.
Hauser RA et al. CNS Spectr. 2022;27(2):208-217.
Jain R. Psych Congress Network. 2020. Accessed April 16, 2023. https://www.hmpgloballearningnetwork.com/site/psychbehav/qas/qa-updates-dr-rakesh-jain-managing-
tardive-dyskinesia.
Miller JJ. Psychiatr Times. 2022;39(8):4-5,25.
Ogino S et al. Psychiatry Clin Neurosci. 2014;68(1):37-49.
Ward KM, Citrome L. Neurol Ther. 2018;7(2):233-248.
Zutshi D et al. Tremor Other Hyperkinet Mov (N Y). 2014;4:266.
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.
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.