Assessing Patients for Tardive Dyskinesia

John M. Kane, MD: Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead; Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, Manhasset; Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York

Because of the serious and potentially irreversible nature of tardive dyskinesia (TD), accurate diagnosis is crucial, but it can present a clinical challenge. The onset of TD is insidious, with fluctuating symptoms that can be masked by or confused with symptoms of other disorders or medication-induced side effects.^1,2 Most commonly, TD will present as involuntary, repetitive, purposeless orofacial movements including chewing; lip smacking, puckering, or pursing; tongue protrusion; grimacing; or bulging of the cheeks.^2–4 TD can also manifest as contracting, twisting, or writhing movements of the fingers, hands, arms, or legs.²

Diagnostic Criteria

The DSM-5¹ criteria for TD simply state that, to receive this diagnosis, an individual should exhibit involuntary movements lasting at least several weeks in association with neuroleptic medication use of at least a few months’ duration. The involuntary movements should be athetoid or choreiform and typically of the tongue, jaw, and extremities. My colleague, Nina R. Schooler, PhD, and I developed a more in-depth set of diagnostic criteria for TD, known as the Schooler-Kane criteria,⁵ that have been widely accepted in clinical practice (AV 1).² The rationales for these criteria are discussed below.

AV 1. Schooler-Kane Criteria for TD Diagnosis (00:52)

Based on Schooler and Kane⁵

Antipsychotic Drug Exposure

Involuntary movements and extrapyramidal symptoms can be observed in untreated patients with schizophrenia. Drug-naive individuals with schizophrenia are significantly more likely to experience movement disorders such as dyskinesias compared with healthy controls (odds ratio = 3.59; 95% CI, 1.53–8.41).⁶ Dopamine dysregulation in specific brain regions may be involved in both the etiology of schizophrenia and the increased risk of movement disorders.⁶ Although the pathophysiology of TD is not fully understood, one hypothesis is that the antipsychotics’ dopamine receptor blocking action in combination with the altered striatal dopamine activity found in individuals with schizophrenia creates an imbalance between direct and indirect pathways of the basal ganglia, which are necessary for normal movement.⁴ Thus, clinicians should evaluate patients for the presence of involuntary movements before initiating antipsychotic treatment to ensure that any pre-existing movements are not later incorrectly attributed to the medication.³ The Schooler-Kane diagnostic criteria⁵ require that patients have at least 3 months of cumulative antipsychotic exposure.

Rating Scales

According to the Schooler-Kane diagnostic criteria,⁵ in order to receive a diagnosis of TD, a patient must exhibit either moderate involuntary movements in 1 or more body areas or at least mild involuntary movement in 2 or more body areas. The presence of these movements should be determined by using a standardized rating scale,⁵ such as the Simpson Dyskinesia Scale,⁷ the Extrapyramidal Symptom Rating Scale,⁸ or the Abnormal Involuntary Movement Scale (AIMS).⁹ However, clinicians must remember that these are screening and not diagnostic tools. These instruments are useful for identifying signs and symptoms of involuntary movement and assessing the severity of these movements, but they should be used in conjunction with diagnostic criteria.

The AIMS was developed by the National Institute of Mental Health as a research tool, but because of its utility for identifying the abnormal, involuntary movements characteristic of TD, it has become widely recommended for use in clinical practice to screen for the involuntary movements required to diagnose TD using the Schooler-Kane criteria.³ The AIMS includes a number of items assessing abnormal movements in different parts of the body, including the face, extremities, and trunk, as well as global assessment items addressing overall severity, impact, and awareness of abnormal movements.

Although the AIMS is a useful tool, clinicians must administer the scale properly in order to obtain accurate and consistent results.¹⁰ The clinician cannot simply observe the patient for a few seconds or a minute. Ideally, the clinician should attempt to discreetly observe the patient at rest, perhaps while he or she is in the waiting room, and also should look for involuntary movements when first greeting the patient.

Once in the office, a more systematic examination can take place, and a firm chair will be needed. The chair should have either no arms or arms that are short enough for the patient’s hands to hang over the ends. The clinician must ask the patient whether there is anything in his or her mouth (like chewing gum) and if so to remove it, about any problems with his or her teeth, and whether dentures are being worn.³ The clinician should also inquire about the patient’s awareness of any involuntary movement.

As the AIMS examination proceeds, the clinician will continually look for any abnormal movements as the patient performs a variety of different movements. The patient should sit in the chair with hands on knees, legs slightly apart, and feet flat on the floor. Then the patient should sit with his or her arms and hands unsupported.

The clinician should ask the patient to open his or her mouth so that the clinician can observe the tongue at rest, and then the patient should be asked to protrude the tongue and keep it extended. Repeating these tongue observations later in the evaluation may be beneficial.

The patient should be asked to rapidly tap his or her thumb to each finger on that hand for 10 to 15 seconds, and then switch to the other hand, while the clinician observes the entire body for any abnormal involuntary movements that may be elicited. The clinician should ask the patient to rise from the chair, walk, and then extend his or her arms in front with palms down, while continually observing the patient’s entire body.

When scoring the AIMS, the clinician should record the incidence of a movement regardless of whether the movement was activated. That is, some clinicians have assigned a lower score to movements that did not appear until they asked the patient to perform an action, and they assigned a higher score to movements that existed when the patient was at rest. But all movements should be rated in the same way. An AIMS score of at least 2 in 2 or more body regions or a score of 3 or 4 in ≥ 1 body region is used for a probable diagnosis of TD with the Schooler-Kane criteria.⁵

According to the American Psychiatric Association (APA),¹¹ all patients taking an antipsychotic medication should be regularly monitored for movement disorders. The APA recommends that patients taking first-generation antipsychotics be assessed every 6 months, whereas patients taking second-generation antipsychotics should be assessed every 12 months. If patients have risk factors for TD (eg, older age, presence of an affective disorder¹²), they should be monitored more frequently. (For a discussion of risk factors for TD, see the activity “Epidemiology and Prevention of Tardive Dyskinesia” by Christoph U. Correll, MD.) Patients at increased risk who are receiving a first-generation antipsychotic should be assessed every 3 months, and patients at increased risk who are receiving a second-generation antipsychotic should be assessed every 6 months.¹¹ If a patient has recently initiated antipsychotic treatment and early involuntary movement has been detected, this patient should be considered at risk for TD and monitored more frequently to determine if the symptoms persist long enough (ie, 3 months) to meet the criteria for TD.^11,12

Case Practice Question

Jonas is a new patient in your clinic who has been taking a second-generation antipsychotic medication for 1 month. Baseline assessment for involuntary movements before Jonas started antipsychotic treatment was not conducted by the referring physician. You assess Jonas using the AIMS and find mild involuntary movements in 2 body areas. Which of the following next steps would be least appropriate?

1. Diagnose Jonas with probable tardive dyskinesia (TD) according to the Schooler-Kane criteria
2. Rule out other conditions that may be causing the motor symptoms
3. Monitor the involuntary movements to see if they persist for 3 months of antipsychotic treatment
4. Review medication indication and dosage to be sure that the agent is needed and Jonas is taking no more than necessary

Preferred response: a.
Explanation: It would be inappropriate to diagnose Jonas with probable TD at this time. According to the Schooler-Kane criteria,5 a patient must have 3 months of antipsychotic treatment before a diagnosis of TD can be made. Jonas has been receiving an antipsychotic for only 1 month. However, Jonas is experiencing potential early signs of TD, and because baseline assessments are not available to determine if involuntary movements were present prior to starting antipsychotic treatment, you should consider him at risk for TD and monitor more frequently than patients without risk factors for TD.

AV 2. Conditions to Consider in the Differential Diagnosis of TD (00:37)

Based on Caroff et al2 and Citrome et al3

Differential Diagnosis

Before diagnosing TD, a clinician must rule out other possible conditions that might be producing the involuntary movements.⁵ Patients who develop dyskinesias after starting antipsychotic treatment should be evaluated for clues to a cause for the dyskinesia, such as family history, sudden onset versus progressive course, or associated medical or neurologic abnormalities.² Once neurologic causes have been eliminated, numerous differential diagnoses must be considered. Conditions that may resemble TD include spontaneous dyskinesia (ie, not associated with antipsychotic exposure), restless leg syndrome, Rett syndrome, senile chorea, Sydenham chorea, autism, chronic motor tic disorder, Tourette syndrome, Huntington disease, Wilson disease, or Meige syndrome, among others (AV 2).^2,3 Additional disorders that may resemble TD are other movement disorders known collectively by the term tardive syndromes, which includes tardive dystonia, tardive akathisia, tardive stereotypy, tardive myoclonus, tardive tourettism, or tardive tremor.⁴ Clinicians must also rule out that the movements are caused by drugs or substances known to be associated with dyskinesias, such as caffeine, antihistamines, stimulants, phenytoin, estrogens, or antidepressants, or even simply caused by oral problems or ill-fitting dentures.^2,3 Once all of these possible explanations for involuntary movements have been eliminated, the patient meets criteria for a diagnosis of probable TD.⁵

Conclusion

Although the sometimes subtle and fluctuating, symptoms of TD can be difficult to identify, clinicians can improve their recognition of this disorder through careful monitoring and consistent use of available tools such as diagnostic criteria and screening instruments. These strategies will enable clinicians to increase early recognition of TD and potentially prevent worsening or persistence of symptoms.

Clinical Points

• Perform baseline assessment to detect any signs of involuntary movement before initiating antipsychotic treatment
• Use an appropriate instrument such as the AIMS to assess all individuals receiving antipsychotic treatment at recommended intervals
• Ensure that a patient experiencing abnormal, involuntary movements has been on antipsychotic treatment for a sufficient length of time before attributing the symptoms to TD
• Ensure the absence of any other conditions that may be causing or contributing to involuntary movements

Abbreviations

AIMS = Abnormal Involuntary Movement Scale, APA = American Psychiatric Association, TD = tardive dyskinesia

References

1. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. Fifth Edition. Washington, DC: American Psychiatric Association; 2013.
2. Caroff SN, Hurford I, Lybrand J, et al. Movement disorders induced by antipsychotic drugs: implications of the CATIE schizophrenia trial. Neurol Clin. 2011;29(1):127–148. PubMed CrossRef
3. Citrome L, Dufresne R, Dyrud JM. Tardive dyskinesia: minimizing risk and improving outcomes in schizophrenia and other disorders. Am J Manag Care. 2007;13(Suppl):1–12.
4. Aquino CCH, Lang AE. Tardive dyskinesia syndromes: current concepts. Parkinsonism Relat Disord. 2014;20(suppl 1):S113–S117. PubMed CrossRef
5. Schooler NR, Kane JM. Research diagnoses for tardive dyskinesia. Arch Gen Psychiatry. 1982;39(4):486–487. PubMed CrossRef
6. Koning JPF, Tenback DE, van Os J, et al. Dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia, first-degree relatives and healthy controls: a meta-analysis. Schizophr Bull. 2010;36(4):723–731. PubMed CrossRef
7. Simpson GM, Lee JH, Zoubok B, et al. A rating scale for tardive dyskinesia. Psychopharmacology (Berl). 1979;64(2):171–179. PubMed CrossRef
8. Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr Res. 2005;76(2–3):247–265. PubMed CrossRef
9. Guy W. ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education, and Welfare; 1976.
10. Bark N, Florida D, Gera N, et al. Evaluation of the routine clinical use of the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). J Psychiatr Pract. 2011;17(4):300–303. PubMed CrossRef
11. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2004;161(suppl):1–56. PubMed
12. Jankelowitz SK. Treatment of neurolept-induced tardive dyskinesia. Neuropsychiatr Dis Treat. 2013;9:1371–1380. PubMed CrossRef

CME Background Information

Supported by an educational grant from Teva Pharmaceuticals.
Participants may receive credit by reading the activity, correctly answering the posttest questions, and completing the evaluation.

Objective

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

• Assess patients for tardive dyskinesia symptoms using standardized screening tools

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 disclosures are as follows:
Dr Kane has received grant/research support from Otsuka and Lundbeck; has received honoraria/consulting fees from Alkermes, Allergan, Forum, Intracellular Therapies, Johnson & Johnson, Janssen, LB Pharmaceuticals, Lundbeck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Sunovion, Takeda, and Teva; and is a stock shareholder of MedAvante, Vanguard Research Group, and LB Pharmaceuticals.
The Chair for this activity, Christoph U. Correll, MD, is a consultant for and has received honoraria from Alkermes, Allergan, Gerson Lehrman Group, IntraCellular Therapies, Janssen/Johnson & Johnson, LB Pharma, Lundbeck, Medavante, Medscape, Neurocrine, Otsuka, Pfizer, Sunovion, Takeda, and Teva; has received grant/research support from Takeda; and has provided expert testimony for Bristol-Myers Squibb, Janssen, and Otsuka.

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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.
To obtain credit for this activity, study the material and complete the CME Posttest and Evaluation.

Release, Review, and Expiration Dates

This brief report activity was published in August 2017 and is eligible for AMA PRA Category 1 Credit™ through August 31, 2020. The latest review of this material was July 2017.

Statement of Need and Purpose

Tardive dyskinesia (TD), a condition characterized by involuntary movements, is usually observed in patients after long-term treatment with antipsychotic agents. Mild early symptoms may be missed by both clinicians and patients because some clinicians fail to describe the risk or screen for initial signs. The potential development of TD among patients taking antipsychotics (or other agents that block dopamine receptors) needs to be monitored and, if it does occur, managed. Treatment options have been limited, but new therapies are emerging to specifically address TD symptoms. Physicians need education about discussing the risk for TD with patients, minimizing the risk, screening patients for early signs of TD, and effectively treating 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 Kane has determined that, to the best of his knowledge, no investigational information about pharmaceutical agents that is outside US Food and Drug Administration–approved labeling has been presented in this activity.

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.

Acknowledgment

This brief report is derived from the planning teleconference series “Emerging Treatment Strategies for Patients With Tardive Dyskinesia,” which was held in April 2017, and supported by an educational grant from Teva Pharmaceuticals. The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher or the commercial supporter.

J Clin Psychiatry, 78(9), e1428. doi:10.4088/JCP.tv17016tx2c