Discussing the Risk of Tardive Dyskinesia With Patients and Screening for Signs

J. Sloan Manning, MD: Department of Family Medicine, University of North Carolina, Chapel Hill, and the Mood Disorders Clinic, Cone Family Practice Center, Greensboro, North Carolina

Based on the webcast What You Should Know About Tardive Dyskinesia: Screening, Causes, and New Treatment Options

Supported by an educational grant from Neurocrine Biosciences, Inc.

Case Introduction

Martha* is a 60-year-old woman who lives alone. She is currently employed as a sales manager at a large car dealership. Martha is divorced and has strained relationships with her 3 married sons who all live in another state.

Medical and Psychiatric History

Martha has a history of panic attacks and mild anxiety that began when she was in college. She was diagnosed with recurrent depression 15 years ago following her divorce; she has experienced more than 5 lifetime episodes with no hospitalizations. For this depressive episode, she has taken multiple antidepressants as well as an unsuccessful trial of adjunctive lithium. Martha’s depression has been labeled as treatment resistant, and she was switched to treatment with 75 mg/d of venlafaxine, a serotonin-norepinephrine reuptake inhibitor. While on this medication, she has experienced significant residual symptoms such as insomnia, anhedonia, and cognitive difficulties, which have caused problems at work.

After 2 months of taking venlafaxine, you suggested that she begin an adjunctive aerobic exercise. She chose water aerobics, since it could also potentially provide relief for her comorbid rheumatoid arthritis,¹ chronic low back pain,² and fibromyalgia.³

*Not a real patient; the patient in this case presentation is a composite based on the author’s clinical experiences.

References

1. Siqueira US, Orsini Valente LG, de Mello MT, et al. Effectiveness of aquatic exercises in women with rheumatoid arthritis: a randomized, controlled, 16-week intervention—the HydRA trial. Am J Phys Med Rehabil. 2017;96(3):167–175. PubMed doi:10.1097/PHM.0000000000000564
2. Dundar U, Solak O, Yigit I, et al. Clinical effectiveness of aquatic exercise to treat chronic low back pain: a randomized controlled trial. Spine. 2009;34(14):1436–1440. PubMed doi:10.1097/BRS.0b013e3181a79618
3. Ortega E, Bote ME, Giraldo E, et al. Aquatic exercise improves the monocyte pro- and anti-inflammatory cytokine production balance in fibromyalgia patients. Scand J Med Sci Sports. 2012;22(1):104–112. PubMed doi:10.1111/j.1600-0838.2010.01132.x

Patient Presentation

Two months have passed since Martha’s last visit, and she is complaining about feeling extremely depressed most days. It has been difficult for her to get up in the morning, and her insomnia, anhedonia, and cognitive difficulties have not improved. Her constant depressed mood has made it hard for her to be motivated at work, and her supervisor has mentioned her decreasing sales quotas. She has no interest in her usual daily activities and has not been attending her water aerobics class regularly.

You discuss the available options with Martha, including their potential adverse effects such as weight gain and tardive dyskinesia (TD). When she asks what TD is, you inform her that involuntary movements may occur after a few months of exposure to antipsychotics. Although first-generation antipsychotics confer the greatest risk of TD, second-generation antipsychotics also confer risk.¹ You explain that catching symptoms early is important in order to reverse or treat them. Together, you decide to combine her venlafaxine treatment with quetiapine for 6 weeks.² You start her dosage of quetiapine at 50 mg/d, which is then titrated to 150 mg/d after 1 week. Due to her age, you decide not to prescribe Martha the maximum dosage.

Given Martha’s treatment history and current symptoms, which assessment should you use to meet her treatment goals going forward?

1. 9-item Patient Health Questionnaire (PHQ-9)
2. Abnormal Involuntary Movement Scale (AIMS)
3. Body mass index (BMI) and/or waist circumference measurement
4. Epworth Sleepiness Scale (ESS)
5. All of the above

References

1. Correll CU. Epidemiology and Prevention of Tardive Dyskinesia. J Clin Psychiatry. 2017. Available at: http://www.cmeinstitute.com/Psychlopedia/Pages/specialtopic/14ets/sec1/section.aspx
2. McIntyre RS, Suppes T, Tandon R, et al. Florida Best Practice Psychotherapeutic Medication Guidelines for adults with major depressive disorder. J Clin Psychiatry. 2017;78(6):703–713. PubMed Full Text

Explanation

The correct answer is e. All of the above

Each of these assessments should be performed before Martha’s treatment is continued.

Guidelines recommend that clinicians regularly monitor patients with a depression rating scale during treatment.¹ The use of scales such as the PHQ-9 can provide clinicians with a simple and regular way to monitor patients’ symptoms and progress toward the treatment goals of a robust, sustained remission and full functional recovery.

Since Martha is being started on a second-generation antipsychotic (SGA) for the first time, it is recommended that a baseline assessment of any abnormal movements be conducted. Martha is at a higher risk for developing tardive dyskinesia (TD) due to her advanced age and the fact that she is female.² The AIMS test is widely recommended for screening for TD.² Certain steps should be taken when administering the exam to patients, such as: unobtrusively observing patients at rest for signs of potential dyskinesia symptoms, providing a firm chair without arms (or with short arms) so that the patient’s hands may hang unsupported, prompting the patient to remove anything they may have in their mouth (such as gum) and inquiring about any problems with their teeth (such as ill-fitting dentures), and asking about the patient’s awareness of any involuntary movements exist.³

SGAs have a tendency to cause significant weight gain⁴ or the onset of diabetes in patients (although rare), so performing an initial BMI and/or waist circumference measurement is necessary to recognize weight gain during treatment.⁵ Additionally, patients with diabetes have a higher risk of developing TD when being treated with SGAs.²

Guidelines for the diagnosis and treatment of insomnia recommend that patients be screened with a tool such as the ESS.⁶ Guidelines¹ for the treatment of depression recommend that patients being treated with an antidepressant who have developed insomnia or other restless behaviors be treated with sleep hygiene techniques or cognitive-behavioral therapy. Other options include adding a sedative-hypnotic medication, trazodone, or melatonin.

References

1. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. Third Edition. Arlington, VA: American Psychiatric Association; 2010.
2. Citrome L, Dufresne R, Dyrud JM. Tardive dyskinesia: minimizing risk and improving outcomes in schizophrenia and other disorders. Am J Manag Care. 2007;12(Suppl). Available at: http://www.ajmc.com/journals/supplement/2007/2007-12-vol12-n1-decisionmakernews/dec07-2760p1-12. Accessed November, 2017.
3. Kane JM. Assessing patients for tardive dyskinesia. 2017. Available at: http://www.cmeinstitute.com/Psychlopedia/Pages/specialtopic/14ets/sec2/section.aspx
4. Bak M, Fransen A, Janssen J, et al. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One. 2014;9(4):e94112. PubMed doi:10.1371/journal.pone.0094112
5. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1–56. PubMed
6. Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487–504. PubMed

Follow-Up Visit

Martha returns after 6 weeks of treatment with venlafaxine and adjunctive quetiapine. She has responded well and her symptoms have improved. You re-administer the assessment tools and schedule a follow-up several weeks later.

At her next follow-up visit, 9 weeks later, Martha complains of uncontrollable movements of her mouth and tongue with some additional involuntary twisting of her shoulders and arms. You administer the AIMS rating scale again, and Martha scores a 2 (indicating mild severity) in both the “Facial and Oral Movements” and “Trunk Movements” categories. Once you have ruled out a diagnosis of spontaneous dyskinesia that sometimes affects the elderly,¹ you determine that Martha meets the Schooler-Kane diagnostic criteria for TD.²

Given this new development in Martha’s condition, what is the best next step in her treatment plan?

1. Lower quetiapine to its original dose of 50 mg/d
2. Discontinue venlafaxine
3. Gradually reduce the dose of quetiapine to zero over several weeks
4. Switch to a different SGA

References

1. Citrome L, Dufresne R, Dyrud JM. Tardive dyskinesia: minimizing risk and improving outcomes in schizophrenia and other disorders. Am J Manag Care. 2007;12(Suppl). Available at: http://www.ajmc.com/journals/supplement/2007/2007-12-vol12-n1-decisionmakernews/dec07-2760p1-12. Accessed November, 2017.
2. Schooler NR, Kane JM. Research diagnoses for tardive dyskinesia. Arch Gen Psychiatry. 1982;39(4):486–487. PubMed doi:10.1001/archpsyc.1982.04290040080014

Explanation

The correct answer is c. Gradually reduce the dose of quetiapine to zero over several weeks

Since Martha has not been diagnosed with schizophrenia and therefore does not need continuing antipsychotic treatment, the best option for her treatment is to discontinue quetiapine immediately using stepwise dose reduction over 2-3 weeks. If TD symptoms are caught early, there is a higher chance that they will remit entirely.¹ Additionally, guidelines² for clinicians treating patients with depression warn about the disadvantages of prescribing a combination of antidepressants and SGAs compared with other antidepressant augmentation strategies.

Considering that quetiapine was not well tolerated and Martha’s unsuccessful response to lithium in the past, other options for her treatment include: switching to a different antidepressant (either within class or across class),² thyroid augmentation such as liothyronine,³ or consideration of repetitive transcranial magnetic stimulation.²

References

1. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1–56. PubMed
2. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. Third Edition. Arlington, VA: American Psychiatric Association; 2010.
3. Touma KTB, Zoucha AM, Scarff JR. Liothyronine for depression: a review and guidance for safety monitoring. Innov Clin Neurocsci. 2017;14(3-4):24–29. PubMed

Follow-up and ConclusionBy 4 weeks after discontinuing her quetiapine, Martha’s TD symptoms have dissipated.

For more information, including video footage of an actual patient demonstrating TD symptoms, please see the webcast, “What You Should Know About Tardive Dyskinesia: Screening, Causes, and New Treatment Options.”

Clinical Points

• Clinicians should regularly screen patients who are being treated with antipsychotic medications in order to detect potential dyskinesia symptoms early.
• For patients who are at a higher risk for developing tardive dyskinesia, clinicians should monitor patients closely and prescribe the lowest recommended dose of antipsychotics.

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Find more articles on this and other psychiatry and CNS topics:
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The Primary Care Companion for CNS Disorders

CME Background Information

Supported by an educational grant from Neurocrine Biosciences, Inc.

To obtain credit for this activity, study the material and complete the evaluation.

Objective

After completing this educational activity, you should be able to:

• Routinely use screening tools to identify early signs of tardive dyskinesia in patients who are prescribed medications associated with its risk

Financial Disclosure

The faculty for this CME activity and the CME Institute staff were asked to complete a statement regarding all relevant personal and financial relationships between themselves or their spouse/partner and any commercial interest. The CME Institute has resolved any conflicts of interest that were identified. No member of the CME Institute staff reported any relevant personal financial relationships. Faculty financial disclosure is as follows:

Dr Manning is a consultant for Otsuka, Sunovion, Takeda, Lundbeck, and Alkermes; and is a member of the speakers/advisory boards for Otsuka, Sunovion, Takeda, and Lundbeck.

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The American Academy of Physician Assistants (AAPA) accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 0.5 hours of Category I credit for completing this program.

Release, Review, and Expiration Dates

This Case and Comment activity was published in November 2017 and is eligible for AMA PRA Category 1 Credit™ through November 30, 2019. The latest review of this material was October 2017.

Statement of Need and Purpose

Some physicians are unaware that tardive dyskinesia (TD) is associated with second-generation antipsychotic (SGA) agents to a greater extent than previously thought. Education about the prevalence and incidence of TD and risk factors and screening tools is needed because SGAs are used to treat multiple illnesses and the older first-generation antipsychotic agents are also still prescribed. Early recognition is key to management of TD, but subtle signs are easily missed if routine standardized screening is not performed. Survey data show that many psychiatrists have not received training on TD, most do not feel competent in using a screening scale, and most do not discuss TD risk with patients before prescribing antipsychotics. Some clinicians continue treatment unchanged after a movement disorder has appeared because patients are responding so positively to the present treatment regimen. Not only does this increase the chances for TD symptoms to become permanent, it can lead to patient nonadherence, which may ultimately lead to relapse. Therefore, education for physicians is also needed about evidence-based treatment options for patients with TD. This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc., who have requested information on TD.

Disclosure of Off-Label Usage

Dr Manning has determined that, to the best of his knowledge, lithium is not approved by the US Food and Drug Administration (FDA) for the adjunctive treatment of major depressive disorder, trazodone is not approved by the FDA for the treatment of insomnia, and melatonin is not approved by the FDA.

Review Process

The entire faculty of the series discussed the content at a peer-reviewed planning session, the Chair reviewed the activity for accuracy and fair balance, and a member of the External Advisory CME Board who is without conflict of interest reviewed the activity to determine whether the material is evidence-based and objective.

Acknowledgement

This Case & Comment activity is derived from the planning teleconference series What You Should Know About Tardive Dyskinesia: Screening, Causes, and New Treatment Options, which was held in May 2017 and supported by an educational grant from Neurocrine Biosciences, Inc.