Earlier Diagnosis of Tardive Dyskinesia

Accurate diagnosis of tardive dyskinesia (TD) is crucial for potential reversal of symptoms, but it can present a clinical challenge due to the insidious onset and fluctuating nature of symptoms. Clinicians may underestimate the risk of TD associated with second-generation antipsychotic (SGA) treatment. While evidence suggests that patients being treated with SGAs have less risk for developing TD than those treated with first-generation antipsychotics (FGAs), the decreased risk is not as great as was originally expected.¹ Additionally, the FGAs are still in use. Therefore, clinicians should review patients’ risk factors and try to prevent TD.^2,3 Regular screening and patient education are important. If patients develop signs of TD, diagnostic tools and criteria should be used. This activity highlights the importance of earlier recognition and diagnosis of TD and provides practical steps.

Epidemiology and Impact of TD

An increase in antipsychotic use has occurred over the past 20 years, with new indications for the use of several antipsychotics as adjunctive treatments for major depression and off-label uses of these medications in children, older persons, and individuals with sleep disturbances (AV 1).^3,4

AV 1. The Global Prevalence Rate of TD Among Patients Taking Antipsychotics

Based on Carbon et al⁴

Although some patients have limited insight into their condition and thus may not be bothered by it, TD is by no means a benign disorder.⁵ Mild cases of TD may be not very noticeable apart from everyday habits, tics, and mannerisms that are commonly ignored by other people. However, moderate to severe movements may be painful, physically disabling, and associated with reduced quality of life, risk of bodily injury, and even death. In high-functioning patients, as antipsychotics are prescribed for more conditions beyond schizophrenia, even mild TD is likely to be experienced as intolerable because of social embarrassment. A recent survey of outpatients with possible TD reported that 70%–80% were aware of their movements and that 50%–60% felt self-conscious about or embarrassed by them.⁵ Over 30% of patients (regardless of psychiatric disorder) reported that involuntary movements had “some” or “a lot” of impact on their ability to continue their usual activities, be productive, and socialize.

Patient Perpectives

An individual living with TD described his feelings of nervousness and social anxiety due to his abnormal movements:

Risk Factors for Developing TD

Several factors have been identified that may place patients at a greater risk of developing TD.⁶ Clinicians should be aware of known risk factors, which include the following:

• Older age
• Female sex
• Longer duration and higher doses of dopamine receptor blocking agents (DRBAs)
• Treatment with typical (first-generation) antipsychotics
• Preexisting mood disorder
• Cognitive disturbance
• Alcohol or substance abuse
• Diabetes
• Human immunodeficiency virus (HIV) positivity
• Early occurrence of extrapyramidal symptoms (EPS)
• African American ethnicity

Although risk factors affect patients’ development of TD, clinicians should consider anyone taking antipsychotics to have some risk and monitor accordingly.⁵

Monitoring and Early Recognition of TD

Because TD may become persistent and irreversible, prevention (if possible) by the conservative use of antipsychotics is critical.³ If TD does develop, early detection is of paramount importance to increase the chances that TD movements will be transient and reversible.⁵

According to the American Psychiatric Association (APA),⁷ all patients should be examined for signs of TD before initiating DRBA therapy, at least biannually in patients taking DRBAs, and upon changes in DRBA dose or agent or observation of previously undetected movements. When prescribing a DRBA, clinicians should get informed consent from the patient, which is prudent practice and may prevent legal consequences. The APA recommends that patients taking FGAs be assessed every 6 months (or every 3 months if they have risk factors for TD), and those taking SGAs should be assessed every 12 months (or every 6 months if they have risk factors for TD).⁷

Patient Perspectives

An individual described the first TD symptoms he noticed:

Screening tools. Monitoring for TD should involve the use of an appropriate tool, such as the Abnormal Involuntary Movement Scale (AIMS).⁸ The AIMS, a 14-item clinician-administered rating scale, has been widely accepted as an objective measure for assessing the severity and extent of TD^5,9 (Table 1).^10,11

Table 1. Instructions for Performing the Abnormal Involuntary Movement Scale (AIMS)

 Click to enlarge Table 1.

Clinicians should make the following considerations when conducting evaluations^12,13:

• Volitional or psychotic mannerisms, tics, and drug-induced parkinsonism must be distinguished from TD but can also coexist with TD.
• The nature and severity of abnormal movements may vary considerably over time. For example, TD can worsen with emotional stress, be more active during movement of other parts of the body (eg, when walking), and disappear entirely during sleep.
• Vigilance is needed because patients may be unaware of their TD movements and therefore may not report symptoms.
• Routine, careful examination can improve identification of TD, but TD can still be difficult to detect early because the antipsychotic agents that cause the underlying pathology can also mask the emergence of symptoms.

Using the full AIMS may be too time-consuming for clinicians in a busy office practice, and suggestions have been made to develop a shorter, simpler AIMS or other instrument.⁵ Another validated rating scale in evaluating extrapyramidal syndromes is the St. Hans Rating Scale (SHRS).¹⁴ The Simpson Abbreviated Dyskinesia Rating Scale¹⁵ can also be used.¹⁶ Additionally, clinicians can inform patients and family members about doing evaluations between clinic visits and advise them to report questionable movements.¹⁷ Because symptoms can fluctuate during the day and over time, patients and family members might observe movements at home that are not caught during the clinical evaluation.

Diagnostic criteria. While an important screening tool, the AIMS cannot be used by itself to diagnose TD. The Schooler-Kane criteria^18,19 for TD require that a patient have ≥3 months of cumulative exposure to neuroleptics, the absence of other conditions that might cause involuntary movements, and at least moderate dyskinetic movements in 1 body area (≥3 rated by the AIMS) or mild dyskinetic movements in 2 body areas (≥2 rated by the AIMS).

Alternative diagnostic criteria that are slightly more inclusive than the Schooler-Kane criteria are the Glazer-Morgenstern criteria.^20,21 These criteria require that the total AIMS score be ≥3, with at least 1 body area rated ≥2 (mild).

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)²² defines TD as a medication-induced movement disorder that persists despite discontinuation or change of medication. Per DSM-5, to confirm a diagnosis of TD, symptoms must persist for 1 month after the medication is discontinued. The involuntary movements should be athetoid or choreiform and typically of the tongue, jaw, and extremities.⁶

Differential Diagnosis of TD

When TD is suspected, clinicians must rule out other conditions associated with abnormal movement.⁶ Symptoms to look for that may suggest a condition other than TD include any rapidly evolving movements, “piano player” movements, isolated dyskinesia of the lower body, or a localized, fixed dystonia only. Conditions that may resemble TD include Huntington disease, drug-induced dyskinesias, edentulous dyskinesia, Wilson’s disease and other metabolic disorders, Tourette syndrome, and immune-mediated choreas.¹⁶

Conclusion

Clinicians have underestimated the risk of TD associated with SGA treatment. In reality, more patients than ever are at risk for this potentially disabling condition. Because TD has the potential to become a permanent condition for some individuals, prevention should be attempted by conservative use of antipsychotics. To minimize the risk of permanence if symptoms do develop, early detection is critical. Diagnosing TD, however, can be challenging due to the insidious onset and fluctuating nature of symptoms. Clinicians must be proactive in following APA guidelines before prescribing antipsychotic therapy and continuing to assess patients throughout treatment. Reliable screening tools and diagnostic criteria (such as the AIMS and the Schooler-Kane criteria) should be used to rule out other conditions associated with abnormal movement and provide a clinical diagnosis as early as possible so that treatment strategies can be implemented.

Clinical Points

• Discuss risk factors and early signs of TD with patients and caregivers
• Examine all patients for TD symptoms before initiating DRBA therapy, and continue to monitor patients throughout treatment with DRBAs
• Use screening tools and diagnostic criteria, such as the AIMS and the Schooler-Kane criteria, to assess patients for TD

© Copyright 2019 Physicians Postgraduate Press, Inc.

Abbreviations

AIMS = Abnormal Involuntary Movement Scale; APA = American Psychiatric Association; DRBA = dopamine receptor blocking agent; DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; EPS = extrapyramidal symptoms; FGA = first-generation antipsychotic; HIV = human immunodeficiency virus; SGA = second-generation antipsychotic; SHS = St. Hans Rating Scale; TD = tardive dyskinesia; VMAT2 = vesicular monoamine transporter 2

From the Series: Early Recognition and Treatment of Tardive Dyskinesia in Patients With Mood Disorders and Schizophrenia
To cite: Kremens DE. Earlier diagnosis of tardive dyskinesia. J Clin Psychiatry. 2020;81(1):NU18041BR1C.
To share: https://doi.org/10.4088/JCP.NU18041BR1C
© Copyright 2019 Physicians Postgraduate Press, Inc.

CME Background Information

Target Audience

Psychiatrists, neurologists, nurse practitioners, and physician assistants

Support Statement

Supported by an educational grant from Neurocrine Biosciences, Inc.

Learning Objective

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

• Recognize early signs of TD through regular screening and patient/family education about symptoms

Release, Review, and Expiration Dates

This brief report activity was published in November 2019 and is eligible for AMA PRA Category 1 Credit™ through November 30, 2021. The latest review of this material was September 2019.

Statement of Need and Purpose

Because some clinicians underestimate the risk of TD, especially with newer antipsychotics, they do not advise patients and caregivers of the risk of TD or educate them about early signs to watch for and report. A substantial proportion of patients with TD do not have a timely diagnosis. Clinicians may not recognize early TD symptoms, as mild cases may be more easily missed. Due to TD movements, patients may stop taking their treatments for mood disorders or schizophrenia. Clinicians may inaccurately rate how bothersome side effects are to patients. New medications for TD are available, and evidence-based treatment recommendations have been published. Recent research has explored longer-term safety and efficacy with newer medications. Clinicians need up-to-date guidance on the prevalence of TD, risk factors for TD, recognition of early signs and symptoms of TD, and assessment tools that will help them diagnose and monitor TD. They also need education about discussing TD risk and signs with patients and family members and should be aware of the burden of TD for patients and families. Up-to-date, evidence-based, expert guidance should be provided on using new medications to treat TD in patients with mood disorders and schizophrenia, including longer-term use. 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 tardive dyskinesia.

Disclosure of Off-Label Usage

Dr Kremens 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 faculty members agreed to provide a balanced and evidence-based presentation and discussed the topics and CME objectives during the planning sessions. The faculty’s submitted content was validated by CME Institute staff, and the activity was evaluated for accuracy, use of evidence, and fair balance by the Chair and a peer reviewer who is without conflict of interest.

Acknowledgment

This activity is derived from the teleconference series “Early Recognition and Treatment of Tardive Dyskinesia in Patients with Mood Disorders and Schizophrenia,” which was held in April—July 2019 and supported by an educational grant from Neurocrine Biosciences, Inc. 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.

Faculty Affiliation

Daniel E. Kremens, MD, JD
Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania

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 Accreditation Council for Continuing Medical Education (ACCME) defines a commercial interest as any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that create a conflict of 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 Kremens is a consultant for Teva, UCB, Sunovion, Impax, Lundbeck, Acadia, USWorldMeds, Adamas, AbbVie, Merz, Allergan, Acorda, Kyowa, Neurocrine, GE Healthcare, and St Jude Medical; is a member of the speakers/advisory boards for Teva, UCB, Impax, Lundbeck, Acadia, USWorldMeds, and Adamas; and has received grant/research support from Acorda and Enterin. The Chair for this activity, Joseph P. McEvoy, MD, has received grant/research support from Takeda, Alkermes, Boehringer Ingelheim, Teva, Neurocrine, and Otsuka; has received honoraria from Neurocrine; and is a member of the speakers/advisory boards for Merck, Neurocrine, and Alkermes.

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 0.50 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Note: The American Nurses Credentialing Center (ANCC) and the American Academy of Physician Assistants (AAPA) accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by the ACCME.

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