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Laura: A Patient With Mood Disorder

Laura-Case-Study

Laura, 43 Years

Laura, 43, a restaurant manager, is divorced and lives with her 23-year-old daughter.

Medical History

  • Diagnosed with bipolar depression at age 22
  • Hospitalized for manic episode at age 26; initiated treatment with a typical APD
  • Attempt to discontinue her APD led to another manic episode and hospitalization at age 32

Family History

  • Her daughter has also been recently diagnosed with bipolar depression

Current Medications

  • Stable on an atypical APD and lithium

22%Increase

in patients taking atypical APDs from 2017 to 2022, driven by their use for mood disorders

1-out-of-4-patients

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

Laura: Medication for Her Mood Disorder Leads to TD

Current Presentation

  • Complains of clenching her jaw (attributes it to increased stress at work), which is painful
  • She notes that she is blinking her eyes more than usual, which has caused some embarrassment
  • Symptoms have caused her to cancel several dates recently

Clinical Examination

  • Excessive blinking, low amplitude movement of the jaw, infrequent brow raising, and puckering of the perioral area

Clinician’s Response to
Examination

  • Refers the patient to the dentist for temporomandibular joint disorder
  • Recommends over-the-counter eye drops for dry eyes

Orofacial movements are among the most common symptoms of TD and often lead to dental problems.

AIMS_Face

Laura: Worsening Symptoms After 3 Months

Presentation at Follow-up Visit

  • Laura continues to complain about clenching her teeth and blinking a lot
  • She reports that customers and colleagues are complaining to the restaurant owner that she is making unpleasant faces at them
  • She has also started to avoid meeting friends and family

Assessment

  • The clinician carefully listens to Laura’s concerns and the impact her symptoms are having
  • Takes a closer look at her facial movements and suspects TD
  • Performs an Abnormal Involuntary Movement Scale (AIMS) assessment

According to American Psychiatric Association (APA) guidelines, mood disorders are a risk factor for TD
in patients taking APDs

Laura’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 and Abnormal Involuntary Movement Scale (AIMS) criteria

Clinicians: What Are Possible Next Steps for Laura?

Red X

APD reduction or withdrawal may fail to improve TD or may induce withdrawal dyskinesia.

Red X

Anticholinergics are not indicated for TD and can make TD symptoms worse. APA guidelines warn against any use of anticholinergics for the treatment of TD.

Checkmark

Vesicular monoamine transporter 2 (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.

Checkmark

While the exact pathophysiology of TD is not fully known, it is thought that chronic blockade of dopamine receptors results in the upregulation of dopamine receptor function. This may increase dopamine signaling, leading to the excessive movement that is characteristic of TD.

Checkmark

APA guidelines recommend treatment if TD, irrespective of severity, has an impact on the patient. Assessment of impact should be performed at every patient visit. The Impact-TD is an easy-to-administer checklist to facilitate the assessment of TD impact in clinical practice

Impact Assessment

  • Laura has noted that her symptoms cause pain and embarrassment
  • She has avoided social situations (eg, dating)
  • Her movements have affected the way customers perceive her in her workplace
  • Impact of TD noted across physical, psychological, social, and vocational domains
  • The degree of impact on Laura’s life warrants consideration of treatment

APA Recommendation

  • APA guidelines recommend VMAT2 inhibitors as first-line treatment for TD that has an impact, irrespective of severity, on the patient.

Treatment With AUSTEDO® Resulted in Statistically Significant TD Symptom Control in the AIM-TD Trial

In the Addressing Involuntary Movements in Tardive Dyskinesia (AIM-TD) trial

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


Patients in the AIM-TD clinical trial received the AUSTEDO BID formulation.

 

In the AIM-TD study, a 12-week, placebo-controlled, fixed-dose trial, adults with TD, ages 21 to 81 years, were randomized 1:1:1:1 to 12 mg of AUSTEDO, 24 mg of AUSTEDO, 36 mg of AUSTEDO, or placebo. The dose of AUSTEDO was started at 12 mg/day and increased at weekly intervals in 6-mg/day increments to a dose target of 12 mg/day, 24 mg/day, or 36 mg/day. The primary efficacy endpoint was change from baseline to Week 12 in AIMS total score in the 36-mg/day group vs placebo, assessed by blinded central video rating.

​
  • In the phase 3 trials for AUSTEDO, the most common adverse events (AEs) were nasopharyngitis and insomnia
  • 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
  • Adverse reactions with AUSTEDO XR are expected to be similar to AUSTEDO BID

Sustained Results Regardless of Underlying Condition

Concurrent Diagnoses at Baseline in RIM-TD

RIM-TD-Diagnoses-Chart

Post Hoc Analysis of the RIM-TD Open-Label Extension: Change in AIMS Total Score From Baseline by Underlying Condition

RIM-TD 3-year changes in AIMS total score; purple represents psychotic disorders and orange represents mood or other disorders

*Mean total daily dose.

Patients in the RIM-TD study received the AUSTEDO BID formulation.

VMAT2 Inhibitors Are Recommended for the Treatment of TD Without the Need to Modify the APD Dose

  • 76% of patients were using APDs in the AUSTEDO TD trials
  • Patients on a stable dose of an antipsychotic maintained that medication while on AUSTEDO

Placebo-Controlled Studies in Patients With TD (ARM-TD and AIM-TD)

Stable Concomitant Medications at Baseline

% (N=335)

Atypical antipsychotics

64

Typical or combination antipsychotics

12

No antipsychotics

24

Patients in the clinical trials received the AUSTEDO BID formulation.

Laura’s Reaction to Diagnosis

Patient Education and
Treatment

  • The clinician educates Laura about TD and how it is caused
  • Proposes treatment with AUSTEDO XR

Laura’s Response

  • Is hesitant to start a new treatment, knowing that the previously prescribed drug caused TD
  • Wants to discontinue treatment with APD for both herself and her daughter

Motivational Interviewing Made the Difference for Laura

Laura’s Decision

  • Through motivational interviewing, Laura was able to work through her hesitancy and commit to continuing treatment with her APD
  • Laura and her clinician focused on achieving attainable goals over the course of 3 months
  • Laura also began treatment for her TD symptoms with AUSTEDO XR
​

Hesitancy to continue APD or start treatment for TD can be addressed by motivational interviewing, a counseling technique for addressing ambivalence about change

Icon of a blue human head and neck with an audio wave coming from his mouth and a question mark, all over a light blue background in a blue circle

Open-Ended Questions

Allow patients to respond without fear of a right or wrong answer

Icon of 2 purple hands surrounding a purple heart in a light purple background enclosed in a purple circle, denoting tender care

Affirmations

Provide support and encouragement, and communicate that what the patient says matters

Icon of a solid orange figure in an orange circle listening to a sound or voice

Reflective Listening

Encourages patients to express their thoughts, which may help them arrive at an idea for change vs telling them what to do

Icon of blue clipboard with lines on it overlayed by magnifying glass shape, the circle filled with a 5-point star, all against a light blue background in a blue circle

Summarization of the Visit

Recaps the visit and calls out the salient elements of the discussion to prevent any misunderstanding

Case Study: Treatment Outcome

Larger version (medium shot) of photo of “Laura,” a TD patient with a mood disorder

Laura

Outcome

  • Laura is currently taking 36 mg/day AUSTEDO XR
  • After 2 weeks, she had a noticeable reduction in involuntary teeth clenching and blinking
  • Over the course of 12 weeks, her symptoms have continued to improve over time

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

​

Thank you for completing

Case Studies: Chapter 1 — Mood Disorder Case

Patient Case: Laura

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

Summary:

As APD use in mood disorders increases, more patients like Laura may be diagnosed with TD. Healthcare professionals may encounter treatment hesitancy in these patients.

Explore the Next Chapter
Joe

Chapter 1 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(8):595-604.

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

Caroff SN. Neuropsychiatr Dis Treat. 2019;15:785-794.

Data on file. Teva Neuroscience.

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

Hauser RA et al. CNS Spectr. 2022;27(2):208-217.

Jackson R et al. J Clin Psychiatry. 2023;84(1):22cs14563.

Jackson R et al. Neuropsych Dis Treat. 2021;17;1589-1597.

Stewart EE, Fox C. Family Pract Manag. 2011;18(3):21-25.

Strassnig M et al. CNS Spectr. 2018;23(6):370-377.

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.