​

Joe: When TD Arises in a Patient Being Treated With Anticholinergics

Photo of “Joe,” a TD patient with schizophrenia

Joe, 55 Years

Joe, 55, was diagnosed with schizophrenia at the age of 24. He lives independently and receives care at a community mental health center (CMHC).

Medical History

  • When initially treated for schizophrenia, Joe exhibited acute signs of DIP and was treated with benztropine
  • He has had no evident symptoms of DIP in the last 5 years

Current Medications

  • Schizophrenia: Long-term injectable typical antipsychotic
  • DIP: Benztropine 1 mg BID

1/3

TD or DIP presents in up to 1/3 of patients taking APDs. Treatment for one movement disorder may worsen the other.

Icon with one dark blue figure and two light blue figures in a blue circle with a white background

Not an actual patient. Image is for illustrative purposes only.

Joe: When TD Arises in a Patient Being Treated With Anticholinergics

Current Clinical Presentation

  • A case manager at the CMHC recently noticed Joe was having difficulty walking

Assessment

  • Joe’s physician diagnosed him with a shuffling gait, which is a breakthrough symptom of DIP

Treatment and Outcomes

  • Over the course of 2 visits, the dose of benztropine was increased twice. His gait improved, but Joe developed jerky movements in his fingers and began grimacing involuntarily
  • The orofacial component prompts the physician to assess Joe with an AIMS exam
Illustration in of a figure walking along a dotted line with lines representing shaking in his neck, arms, and hips

A history of any medication-induced movement disorder is a risk factor for TD.

Joe’s AIMS Exam Confirms TD

MOVEMENT RATINGS SCORE
Facial & Oral
Movements		 1.

Muscles of facial expression

 01234
2.

Lips and perioral area

 01234
3.

Jaw

 01234
4.

Tongue

 01234
Extremity
Movements		 5.

Upper (arms, wrists, hands, fingers)

 01234
6.

Lower (legs, knees, ankles, toes)

 01234
Trunk Movements 7.

Neck, shoulders, hips

 01234
Global Judgments 8.

Severity of abnormal movements overall

 01234
9.

Incapacitation due to abnormal movements

 01234
10.

Patient awareness of abnormal movements

 01234
Dental Status 11.

Current problems with teeth/dentures?

 NOYES
12.

Are dentures usually worn?

 NOYES
Total AIMS Score = 7

Diagnosis

  • TD, based on visual assessment with the AIMS exam and Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR) criteria

Impact of TD on Joe’s Life

Presentation at Follow-up Visit

  • Joe’s hand movements and facial grimacing have caused embarrassment and led to withdrawal from social situations
  • The impact on Joe’s social life warrants consideration for treatment
Sketch of hand inside a blue circle, shaded in purple Sketch of head inside a blue circle, with mouth area shaded in purple

American Psychiatric Association (APA) Guidelines Recommend VMAT2 Inhibitors as First-line Treatment for TD Regardless of Severity

APA Recommendation

  • VMAT2 inhibitors, such as AUSTEDO XR®, are recommended for the treatment of TD that has an impact on the patient*

*The APA recommends that patients who have moderate to severe or disabling TD associated with antipsychotic therapy be treated with a reversible inhibitor of the VMAT2. APA guidelines recommend considering a VMAT2 inhibitor to address TD-associated impairments and impact on social functioning.

The Efficacy of AUSTEDO® Was Demonstrated
in Clinical Trials in TD

Aim to Reduce Movements in
Tardive Dyskinesia (ARM-TD)
(N=113)
Flexible-dose trial*

12-week, randomized, double-blind, placebo- controlled trial in which doses were titrated to an individualized dose that reduced abnormal movements and was tolerated

Addressing Involuntary Movements
in Tardive Dyskinesia (AIM-TD)
(N=222)
Fixed-dose trial†

12-week, randomized, double-blind, placebo- controlled trial in which patients received a dose of 0 mg (placebo), 12 mg, 24 mg, or 36 mg

Reducing Involuntary Movements in Participants With Tardive Dyskinesia (RIM-TD)
(N=343)

Open-label, long-term maintenance study

Patients who successfully completed ARM-TD or AIM-TD were eligible to enroll after discontinuing drug for at least 1 week and beginning treatment at a dose of 12 mg/day and titrating for up to 6 weeks. Patients were followed for ~3 years

​

*In ARM-TD, study drug was started at 12 mg/day (6 mg BID) and titrated weekly by 6 mg/day, if required, for up to 6 weeks until adequate dyskinesia control was achieved, a significant adverse event (AE) occurred, or the maximal allowable dose (48 mg/day) was reached.

†In AIM-TD, study drug was started at 12 mg/day and increased at weekly intervals in 6-mg/day increments to a dose target of 12 mg, 24 mg, or 36 mg/day.

ARM-TD Showed Rapid and Meaningful Symptom Control in a Dose-Titration Study

Change in AIMS Total Score From Baseline to Week 12

Chart of ARM-TD changes in AIMS scores to Week 12 with one purple line and one gray line.]

Results were consistent in the AIM-TD study at Week 12:

  • Placebo: 1.4-point reduction versus baseline
  • 36 mg/day: 3.3-point reduction versus baseline
  • −1.9-point treatment effect versus placebo (P=0.001)

Baseline AIMS total scores were similar between AUSTEDO and placebo: AUSTEDO 9.7 (SD, 4.1); placebo 9.6 (SD, 3.8).

Safety and Tolerability Were Shown in Clinical Studies

Placebo-Controlled TD Studies: Adverse Reactions Reported in ≥2% of Patients Treated With AUSTEDO

Adverse Reaction AUSTEDO
(n=279)		 Placebo
(n=131)
Headache 5% 8%
Somnolence 4% 7%
Diarrhea 4% 4%
Nasopharyngitis 4% 2%
Fatigue 4% 5%
Insomnia 4% 1%
Anxiety 4% 5%
Upper respiratory tract infection 3% 4%
Dry mouth 3% 5%
Nausea 2% 7%
Weight increased 2% 3%
Urinary tract infection 2% 2%
Depression/Dysthymic disorder 2% 1%
Akathisia/Agitation/
Restlessness		 2% 1%
Arthralgia 2% 1%

Of patients taking AUSTEDO:

  • Discontinuation due to AEs occurred in 4% of patients vs 3% of patients on placebo
  • Dose reduction due to AEs was required in 4% of patients vs 2% of patients taking placebo

Once patients were titrated to their maintenance dose, the following AEs were no longer reported

  • Dry mouth, nausea, and hypertension (AIM‑TD)
  • Somnolence and dry mouth (ARM-TD)

Adverse reactions with AUSTEDO XR are expected to be similar to AUSTEDO BID

Patients in the AIM-TD, ARM-TD, and RIM-TD clinical trials received the AUSTEDO BID formulation.

See How Joe’s Symptoms Were Addressed With Appropriate Treatment

Change in APD

  • Joe discontinued the long-acting injectable (LAI) typical APD and began treatment with a LAI atypical APD
  • Schizophrenia symptoms remained stable once optimized on new treatment
  • Gait improved and stabilized

Reduction in Anticholinergic Use

  • Anticholinergics are not indicated in patients with TD and can worsen TD symptoms
  • Benztropine 3 mg BID was discontinued by tapering
  • Reduced gradually from 3 mg BID to 2 mg BID to 1 mg BID before discontinuing

Treatment of TD With a VMAT2 Inhibitor

  • After discontinuation of benztropine, Joe initiated treatment with AUSTEDO XR
  • After 2 weeks on therapy, Joe noticed a reduction in jerky hand movements and facial grimacing
  • Over the next 4 weeks, his symptoms continued to improve
  • Joe is currently on 36 mg/day of AUSTEDO XR
​

Thank you for completing

Case Studies: Chapter 2 — DIP vs TD Case Study

Patient Case: Joe

Orange clipboard with checkmarks next to 3 lines, surrounded by an orange circle.

Summary:

TD and DIP are common movement disorders in patients taking APDs. As seen in Joe’s case, accurate diagnosis is crucial, because anticholinergic treatment indicated for DIP may exacerbate TD.

Explore the Next Chapter
Chris

Chapter 2 References:

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

American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. Washington, DC:

American Psychiatric Association; 2021.

Anderson KE et al. Lancet Psychiatry. 2017;4:595-604.

AUSTEDO XR® (deutetrabenazine) extended-release tablets/AUSTEDO® current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.

Carbon M et al. J Clin Psychiatry. 2017;78(3):e264-e278.

Data on file. Teva Neuroscience, Inc. Parsippany, NJ.

Fernandez HH et al. Neurology. 2017;88(21):2003-2010.

Guy W. ECDEU Assessment Manual for Psychopharmacology: Revised. Rockville, MD; 1976:534-537.

Hauser RA et al. Front Neurol. 2022;13:773999.

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

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.