Discussion Guides: Tardive Dyskinesia Roundtable Webinar

Expert Perspectives® in Tardive Dyskinesia 2024 – Discussion Guides

Practical Considerations when Initiating Therapy for Tardive Dyskinesia

What are some key considerations and concerns when initiating therapy for patients with tardive dyskinesia?

Overview

Tardive dyskinesia (TD) is a debilitating, often irreversible movement disorder caused by prolonged exposure to dopamine receptor blocking agents (DRBAs) like antipsychotics. The recent approval of vesicular monoamine transporter 2 (VMAT2) inhibitors provides evidence-based treatment options for TD. Initiating therapy requires careful patient assessment, selection of appropriate treatment, and monitoring for efficacy and adverse effects. Contemporary guidelines emphasize early recognition, screening with validated tools, and using VMAT2 inhibitors as first-line treatments.

Early Recognition and Assessment

Early recognition and assessment of TD are crucial for effective management. The Abnormal Involuntary Movement Scale (AIMS) is frequently used to assess TD severity and monitor treatment response over time, aiding in the early detection of dyskinetic movements and guiding therapeutic decisions (Debrey & Goldsmith 2021). Establishing a baseline assessment with AIMS before treatment initiation allows for accurate monitoring of treatment response and potential adverse effects (Debrey & Goldsmith 2021).

Risk Factors and Patient History

Identifying patients at higher risk for developing TD is essential. Risk factors include older age (defined as those with a mean age of 65 years), female sex, African American ethnicity, history of substance abuse, and prolonged use of DRBAs (Debrey & Goldsmith 2021). A thorough patient history, including previous and current medication use, is necessary to tailor the treatment plan (Debrey & Goldsmith 2021).

Medication Review and Adjustment

Reviewing the patient's current medication regimen is a critical step. If possible, reducing the dose or discontinuing the offending agent may be beneficial. (Factor 2020). Switching from a first-generation antipsychotic (FGA) to a second-generation antipsychotic (SGA) with a lower risk of TD, such as clozapine, may also be considered (Factor 2020).

First-Line Treatment Options

VMAT2 inhibitors, including valbenazine and deutetrabenazine, are the first-line treatments for TD. These agents have shown significant efficacy in reducing TD symptoms and are generally well-tolerated. Concomitant medications, including strong CYP2D6 inhibitors, should also be considered, as they may affect the metabolism and dosing of VMAT2 inhibitors (Ricciardi 2019).

Valbenazine is a highly selective VMAT2 inhibitor metabolized into active metabolites with a long half-life, allowing for once-daily dosing (Brasic 2021). Deutetrabenazine, a deuterated form of tetrabenazine, has a longer half-life and reduced peak-to-trough fluctuations, enabling twice-daily dosing (Bahroo & Gandhy 2017). The choice between these agents should be based on patient-specific factors, including comorbid conditions and potential for drug interactions (Debrey & Goldsmith 2021 & Factor 2020 & Virameteekul & Bhidayasiri 2023)

Monitoring and Managing Adverse Effects

Monitoring for adverse effects is essential when initiating VMAT2 inhibitors. Common side effects include somnolence, fatigue, and potential for QTc prolongation. Regular follow-up visits and appropriate dose adjustments can help manage these adverse effects (Debrey & Goldsmith 2021 & Factor 2020 & Virameteekul & Bhidayasiri 2023).

Patient Education and Support

Educating patients and their families about TD, its potential causes, and treatment options is crucial. Providing support and addressing concerns can improve adherence to treatment and overall outcomes (Debrey & Goldsmith 2021 & Factor 2020).

Conclusion

Initiating therapy for tardive dyskinesia requires a comprehensive approach that includes early recognition and assessment using validated tools like the AIMS, identifying risk factors through a thorough patient history, reviewing and adjusting current medications if possible, and considering VMAT2 inhibitors like valbenazine and deutetrabenazine as first-line treatments. Careful monitoring for efficacy and adverse effects, along with patient education and support, is crucial for successful management of this debilitating and often irreversible movement disorder.

References

Bahroo L, Gandhy R. Tardive Dyskinesia: A New Treatment for an Old Disorder. Pract Neurol. Published June 2017. Accessed June 17, 2024. https://practicalneurology.com/articles/2017-june/tardive-dyskinesia-a-new-treatment-for-an-old-disorder

Brasic JR. Tardive Dyskinesia. Medscape. Updated November 16, 2021. Accessed June 17, 2024. https://emedicine.medscape.com/article/1151826-overview#a11

Debrey SM, Goldsmith DR. Tardive Dyskinesia: Spotlight on Current Approaches to Treatment. Focus (Am Psychiatr Publ). 2021;19(1):14-23. doi:10.1176/appi.focus.20200038

Factor SA. Management of Tardive Syndrome: Medications and Surgical Treatments. Neurotherapeutics. 2020;17(4):1694-1712. doi:10.1007/s13311-020-00898-3

Ricciardi L, Pringsheim T, Barnes TRE, et al. Treatment Recommendations for Tardive Dyskinesia. Can J Psychiatry. 2019;64(6):388-399. doi:10.1177/0706743719828968

Virameteekul S, Bhidayasiri R. Emerging treatments for tardive syndrome: Practical approaches and novel therapeutic strategies. Pract Neurol. 2023;33(5):38-41

The Role of Telehealth in the Management of Tardive Dyskinesia

Given the emerging role of telehealth in the management of tardive dyskinesia (TD), what are some significant challenges and opportunities in integrating telehealth into routine clinical practice for TD?

Overview

Telehealth has emerged as a significant modality in healthcare delivery, particularly accelerated by the COVID-19 pandemic. The application of telehealth in managing tardive dyskinesia (TD), a drug-induced movement disorder associated with prolonged use of dopamine receptor-blocking agents, is increasingly explored. Current insights into the role of telehealth in TD management highlight benefits, challenges, and best practices based on recent literature and expert panel discussions.

Benefits of Telehealth in TD Management

The primary advantage of telehealth in managing TD is improved access to care. Patients can consult with specialists without the need to travel, which is particularly beneficial for those in rural or underserved areas​​​​ (McEvoy 2021 & El-Mallakh 2023).

Telehealth can reduce missed appointments, ensuring consistent monitoring and management of TD (El-Mallakh 2023). It also allows family members and caregivers to participate in consultations, providing a fuller understanding of the patient's condition (El-Mallakh 2023). Additionally, telehealth offers increased convenience, privacy, cost-effectiveness, and reduced exposure to infectious diseases (Handzel 2021).

Challenges of Telehealth in TD Management

Despite its benefits, telehealth presents several challenges in the management of TD. The primary issue is the difficulty in conducting thorough neurological assessments (Chepke 2022).

However, evidence suggests that remote assessments for TD using the Abnormal Involuntary Movement Scale (AIMS) are valid and reliable (Chepke 2022). A study in 2011 demonstrated that virtual AIMS exams were as reliable as in-person exams for detecting abnormal movements (Chepke 2022). Additionally, clinical trials for FDA-approved treatments for TD, such as deutetrabenazine and valbenazine, utilized remote movement disorder neurologists to assess pre-recorded videos of on-site AIMS exams, further validating the use of telemedicine for TD evaluations (Chepke 2022).

Technical problems such as poor video quality, inadequate lighting, and segmented views of the patient's body can impede the accurate observation of involuntary movements (El-Mallakh 2023)​​. Additionally, telehealth may not be suitable for initial diagnoses that require comprehensive in-person evaluations (McEvoy 2021).

Best Practices for Telehealth in TD Management

Experts recommend several best practices to optimize the use of telehealth in managing TD. First, it is essential to combine telehealth with periodic in-person visits (El-Mallakh 2023 & Chepke 2022). An initial in-person assessment should be conducted within six months before the first virtual visit, followed by at least one in-person assessment every six months thereafter​​ (El-Mallakh 2023)​​.

To prepare for a virtual TD assessment, it is recommended to have a staff member call the patient beforehand to test their hardware, software, and internet connection (Chepke 2022). Patients should be instructed to find a well-lit, private location with adequate space, and to use a device that can capture a wide-angle view of their entire body, such as a laptop or desktop computer (Chepke 2022). During the assessment each body region should be observed for at least 10 seconds, and the clinician may need to guide the patient to reposition the camera or move their chair to obtain a clear view of different body parts (Chepke 2022). If a reliable observer, such as a family member or caregiver, is available, they can assist in the assessment and provide additional information about the patient's functioning (Chepke 2022). During telehealth sessions, the use of video is crucial, as audio-only interactions are insufficient for evaluating TD​​ (El-Mallakh 2023)​​.

Furthermore, involving family members or caregivers during telehealth visits can provide valuable insights into the patient's symptoms and help in treatment adherence​​​​ (McEvoy 2021 & El-Mallakh 2023). Pre-appointment instructions should be given to patients to ensure they are well-prepared with the necessary technology and environment for the virtual visit El-Mallakh 2023)​​.

Conclusion

Telehealth is a valuable tool in the management of TD, offering benefits such as improved access to care and enhanced patient and caregiver involvement. However, it is not without challenges, particularly in conducting thorough neurological assessments. Combining telehealth with regular in-person visits and following best practices can help mitigate these challenges and optimize patient outcomes. As telehealth continues to evolve, ongoing education and adaptation of telehealth protocols will be crucial in effectively managing TD and other movement disorders.

References

Chepke C. Telemedicine Strategies to Assess and Manage Tardive Dyskinesia. MedCentral. Last updated July 2022. Accessed June 17, 2024. https://www.medcentral.com/neurology/tardive-dyskinesia/telemedicine-strategies-to-assess-and-manage-tardive-dyskinesia

El-Mallakh RS, Belnap A, Iyer S, et al. Telehealth for Assessing and Managing Tardive Dyskinesia: Expert Insights from a Cross-Disciplinary Virtual Treatment Panel. Telemed J E Health. 2023;29(7):1096-1104. doi:10.1089/tmj.2022.0234.

Handzel S. How Telehealth Can Help People With Tardive Dyskinesia. HealthGrades. Last reviewed January 2021. Accessed June 17, 2024. https://www.healthgrades.com/right-care/schizophrenia/how-telehealth-can-help-people-with-tardive-dyskinesia?tpc=treating-tardive-dyskinesia&did=t11_rss4&cb=ap

McEvoy JP. The Assessment of Tardive Dyskinesia Via Telepsychiatry. Clinical Care Options. Published May 2021. Accessed June 17, 2024. https://clinicaloptions.com/CE-CME/assessing-td-via-telepsychiatry/100008679/content

Competing Theories on the Pathophysiology of Tardive Dyskinesia

Which mechanisms for the pathophysiology of tardive dyskinesia offer the most promising targets for intervention based on current evidence? What additional studies are needed to clarify these pathways?

Overview

Tardive dyskinesia (TD) is a debilitating movement disorder often associated with long-term use of antipsychotic medications. Despite extensive research, the exact pathophysiology of TD remains elusive. Multiple theories have been proposed to explain its underlying mechanisms, each contributing unique insights into this complex condition.

Dopamine Receptor Supersensitivity

The most widely accepted theory suggests that TD results from dopamine receptor supersensitivity, particularly involving the dopamine D2 receptors (Takeuchi 2022 & Caroff 2019). Chronic blockade of these receptors by antipsychotics is proposed to lead to compensatory upregulation or increased sensitivity of postsynaptic dopamine receptors in the striatum (Takeuchi 2022 & Caroff 2019). This hypothesis is supported by the observation that TD is unique to treatment with dopamine D2 receptor antagonists and can be suppressed by drugs that deplete or block dopamine activity (Caroff 2019).

Oxidative Stress and Neurotoxicity

Another significant theory centers on oxidative stress and neurotoxicity. According to this theory, antipsychotics can cause an increase in the production of free radicals, which act as neurotoxins and contribute to the development of TD (Takeuchi 2022 & Ali 2020). Antipsychotic-induced blockade of dopamine D2 receptors is proposed to lead to increased dopamine synthesis and metabolism, resulting in elevated levels of reactive oxygen species and subsequent oxidative damage to neuronal cells (Takeuchi 2022 & Ali 2020).

Gamma-Aminobutyric Acid (GABA) Dysfunction

This theory proposes that prolonged dopamine D2 receptor blockade by antipsychotics results in damage to GABAergic neurons in the striatum, leading to dysregulation of the direct and indirect basal ganglia pathways and subsequent motor abnormalities (Takeuchi 2022 & Ali 2020). This imbalance is thought to contribute to the development of abnormal movements characteristic of TD.

Neuroplasticity and Synaptic Changes

Recent evidence suggests that TD may result from maladaptive synaptic plasticity, involving presynaptic, synaptic, and postsynaptic changes (Tanner 2023 & Virameteekul & Bhidayasiri 2023). Chronic D2 receptor blockade is proposed to increase presynaptic dopamine release, leading to higher vesicular dopamine concentrations and increased synaptic dopamine levels (Tanner 2023). This may contribute to the formation of perforated synapses, an early step in new synapse formation (Tanner 2023). Additionally, postsynaptic changes, such as increased D2 receptor expression, have been observed without evidence of increased sensitivity or potency (Tanner 2023).

Genetic Factors

Genetic factors contributing to the pathophysiology of TD include variations in dopamine and serotonin receptor genes, oxidative stress-related genes, and metabolic enzymes (Tsermpini 2022). Polymorphisms in the dopamine receptor-2 (DRD2) gene affect dopamine receptor function, while variants in hydroxytryptamine receptor-2a (HTR2A) and hydroxytryptamine receptor-2c (HTR2C) genes influence serotonin receptor expression, both linked to increased TD risk (Tsermpini 2022). Additionally, polymorphisms in cytochrome P450 family (CYP1A2 and CYP2D6) enzymes impact drug metabolism, and genes like superoxide dismutase-2 (SOD2) related to oxidative stress may exacerbate neurotoxic effects of antipsychotics, highlighting the complex genetic interplay in TD development (Tsermpini 2022).

Conclusion

The pathophysiology of TD involves various interconnected mechanisms, including dopamine receptor supersensitivity, oxidative stress, GABA dysfunction, neuroplasticity changes, and genetic factors. These multifactorial mechanisms underscore the complexity of TD and the need for diverse therapeutic approaches.

References

Ali Z, Roque A, El-Mallakh RS. A unifying theory for the pathoetiologic mechanism of tardive dyskinesia. Med Hypotheses. Published online March 16, 2020. doi:10.1016/j.mehy.2020.109682

Caroff SN. Recent Advances in the Pharmacology of Tardive Dyskinesia. J Clin Psychopharmacol. 2019;39(3):254-263. doi:10.1097/JCP.0000000000001027

Takeuchi H, Mori Y, Tsutsumi Y. Pathophysiology, prognosis and treatment of tardive dyskinesia. Ther Adv Psychopharmacol. 2022;12:20451253221117313. doi:10.1177/20451253221117313

Tanner CM, Caroff SN, Cutler AJ, et al. Impact of possible tardive dyskinesia on physical wellness and social functioning: results from the real-world RE-KINECT study. J Patient Rep Outcomes. 2023;7(1):21. Published 2023 Mar 9. doi:10.1186/s41687-023-00551-5

Tsermpini EE, Redenšek S, Dolžan V. Genetic Factors Associated With Tardive Dyskinesia: From Pre-clinical Models to Clinical Studies. Front Pharmacol. 2022;12:834129. Published 2022 Jan 24. doi:10.3389/fphar.2021.834129

Virameteekul S, Bhidayasiri R. Emerging treatments for tardive syndrome: Practical approaches and novel therapeutic strategies. Pract Neurol. 2023;33(5):38-41

Modifiable Risk Factors for Tardive Dyskinesia

What are some modifiable risk factors for tardive dyskinesia? What strategies have you implemented to prevent and mitigate TD in your patients, considering factors like antipsychotic type and dosage, substance use, and co-treatment with other medications?

Overview

Tardive dyskinesia (TD) is a severe, often irreversible movement disorder induced by chronic exposure to dopamine receptor blocking agents (DRBAs), including antipsychotics. Identifying and managing modifiable risk factors is crucial for preventing and mitigating TD.

Comorbidity-Related Risk Factors

Diabetes Mellitus: Patients with diabetes mellitus have a higher risk of developing TD (Solmi 2018 & Saklad 2020). This association is observed in patients treated with antipsychotics for major psychotic disorders and those using metoclopramide for gastrointestinal diseases (Solmi 2018 & Saklad 2020. Optimizing diabetes management and avoiding drugs that worsen metabolic profiles are recommended strategies (Solmi 2018 & Saklad 2020).

Smoking: Smoking is significantly more prevalent among patients with mental illnesses, particularly those with bipolar disorder and schizophrenia (Solmi 2018 & Saklad 2020 & Ghosn 2021). There is a strong correlation between the amount of cigarette consumption and the severity of TD (Solmi 2018 & Saklad 2020 & Ghosn 2021). Smoking cessation interventions should be offered to patients on DRBAs, and adjustments in the dose of certain antipsychotics like olanzapine and clozapine may be necessary due to accelerated metabolism in smokers (Solmi 2018 & Saklad 2020 & Ghosn 2021).

Alcohol and Substance Abuse: The prevalence of substance abuse, including alcohol and cocaine, is high among individuals with mental illnesses (Solmi 2018 & Saklad 2020 & Ghosn 2021). These substances are associated with an increased risk of TD. Preventing and treating substance abuse is essential to reduce the risk of TD (Solmi 2018 & Saklad 2020 & Ghosn 2021).

Treatment-Related Risk Factors

Type of Antipsychotic: First-generation antipsychotics (FGAs) are associated with a higher risk of TD compared to second-generation antipsychotics (SGAs) (Solmi 2018 & Saklad 2020 & Ghosn 2021). Among SGAs, those with lower dopamine D2 receptor and serotonin 5-hydroxytryptamine receptor (D2-5HT2A) affinity ratios or partial D2 agonist activity are preferred. Clozapine, in particular, has a lower propensity to induce TD (Solmi 2018 & Saklad 2020 & Ghosn 2021).

Antipsychotic Dose and Duration: Higher doses and longer durations of antipsychotic treatment are linked to an increased risk of TD (Solmi 2018 & Saklad 2020 & Ghosn 2021). Using the minimal effective dose and avoiding high cumulative doses are recommended (Solmi 2018 & Saklad 2020 & Ghosn 2021). Regular monitoring of antipsychotic plasma levels can help optimize treatment and reduce TD risk (Solmi 2018 & Saklad 2020 & Ghosn 2021).

Acute Motor Syndromes: The development of acute motor syndromes such as parkinsonism, acute dystonia, and akathisia during antipsychotic treatment is a predictor of later TD (Solmi 2018 & Saklad 2020 & Ghosn 2021). Avoiding dose increases that lead to these side effects and considering antipsychotics with a lower propensity for acute motor syndromes are important preventive measures (Solmi 2018 & Saklad 2020 & Ghosn 2021).

Intermittent Antipsychotic Treatment: Intermittent treatment or "drug holidays" can increase the risk of TD (Solmi 2018 & Saklad 2020 & Ghosn 2021). Consistent adherence to antipsychotic treatment and implementing slow taper strategies when discontinuation is planned are recommended to minimize this risk (Solmi 2018 & Saklad 2020 & Ghosn 2021).

Anticholinergic Co-treatment: The use of anticholinergic medications to mask acute motor syndromes can increase the risk of TD (Solmi 2018 & Saklad 2020 & Ghosn 2021). Avoiding anticholinergic co-treatment and addressing the underlying motor symptoms directly are advised (Solmi 2018 & Saklad 2020 & Ghosn 2021).

VMAT-2 Inhibitors: Medications like deutetrabenazine and valbenazine have been shown to be effective in managing TD by reducing dopamine release, thereby decreasing dyskinetic movements (Ghosn 2021).

Conclusion

Managing modifiable risk factors is essential for preventing and mitigating TD. Clinicians can focus on optimizing the treatment of comorbid conditions, choosing antipsychotics with lower TD risk, using the minimal effective doses, and avoiding practices that increase TD risk. Regular monitoring and early intervention are key strategies in managing patients on DRBAs. Medications like deutetrabenazine and valbenazine have been shown to be effective in managing TD by reducing dopamine release, thereby decreasing dyskinetic movements.

References

Ghosn O, Ye E, Huege S. Evaluating and Managing Tardive Dyskinesia in the Older Adult. Curr Geri Rep. 2021;10:108-115. doi:10.1007/s13670-021-00364-8

Saklad SR. Identifying Tardive Dyskinesia: Risk Factors, Functional Impact, and Diagnostic Tools. J Clin Psychiatry. 2020;81(1):TV18059BR1C. Published 2020 Jan 14. doi:10.4088/JCP.TV18059BR1C

Solmi M, Pigato G, Kane JM, Correll CU. Clinical risk factors for the development of tardive dyskinesia. J Neurol Sci. 2018;389:21-27. doi:10.1016/j.jns.2018.02.012

Employing Evidence-Based Management Strategies for Tardive Dyskinesia

What are the biggest challenges in implementing evidence-based strategies for tardive dyskinesia in patients, and how do you address these, particularly in ensuring patient adherence and optimizing outcomes?

Overview

Tardive dyskinesia (TD) is a severe, often persistent movement disorder associated with prolonged use of dopamine receptor blocking agents (DRBAs), particularly antipsychotics. Effective management of TD requires evidence-based strategies that focus on prevention, early detection, and optimal treatment.

Prevention Strategies

Prevention: An important strategy for managing TD is prevention (Jenna 2022 & Correll 2021 & Caroff 2019). This involves using second-generation antipsychotics (SGAs) over first-generation antipsychotics (FGAs) due to their lower risk of inducing TD. Clinicians are encouraged to prescribe the lowest effective dose and regularly monitor patients for early signs of TD using structured assessment tools like the Abnormal Involuntary Movement Scale (AIMS) (Jenna 2022 & Correll 2021 & Caroff 2019). Clinicians should follow best practices for prescribing antipsychotics, including limiting their use to specific indications, using the minimum effective dose, and minimizing the duration of therapy (Ricciardi 2019).

Early Detection: Regular screening for TD is crucial. The American Psychiatric Association (APA) recommends routine assessments every 6 months for patients on FGAs and annually for those on SGAs. High-risk patients should be screened more frequently (Jenna 2022 & Correll 2021 & Caroff 2019).

Pharmacological Management Strategies

VMAT2 Inhibitors: The most robust evidence supports the use of vesicular monoamine transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, which are FDA-approved for treating TD. These medications reduce the severity of dyskinetic movements by inhibiting the uptake of dopamine into presynaptic vesicles (Jenna 2022 & Correll 2021 & Caroff 2019).

• Valbenazine: Administered once daily, valbenazine has shown significant efficacy in reducing TD symptoms with a favorable side effect profile.
• Deutetrabenazine: Taken twice daily, deutetrabenazine also effectively reduces TD symptoms and is associated with fewer side effects compared to tetrabenazine.

Dose Adjustments

If TD symptoms develop, the first-line approach is to taper and discontinue the offending DRBA, if clinically feasible (Vaidyanathan 2020). However, for many patients with severe mental illness, discontinuing antipsychotics may not be possible due to the risk of relapse. In such cases, switching from an FGA to an SGA with lower dopamine D2 receptor affinity, such as clozapine or quetiapine, may be effective in reducing TD symptoms (Ricciardi 2019 & Pardis 2019).

Non-Pharmacological Strategies

Patient and Caregiver Education: Clinicians are encouraged to discuss lifestyle modifications that can help manage symptoms and improve overall quality of life. Educating patients and caregivers about the risks of TD, early signs to watch for, and available treatment options is essential. This includes discussing the potential benefits and side effects of VMAT2 inhibitors (Jenna 2022 & Correll 2021 & Caroff 2019).

Comprehensive Management Approach

Regular Monitoring: Using tools like the AIMS for routine assessment and documentation of TD symptoms (Jenna 2022 & Correll 2021 & Caroff 2019).

Informed Decision-Making: Engaging patients and caregivers in discussions about treatment goals and medication preferences such as for the newly approved sprinkle formulation of valbenazine, for those with swallowing difficulties. (Jenna 2022 & Correll 2021 & Caroff 2019 & Package Insert).

Multidisciplinary Care: Collaborating with neurologists, psychiatrists, and other healthcare providers to optimize treatment plans and address the multifaceted needs of patients with TD (Jenna 2022 & Correll 2021 & Caroff 2019).

Conclusion

Employing evidence-based management strategies for TD involves a combination of preventive measures, regular monitoring, pharmacological treatments, and patient education. VMAT2 inhibitors, such as valbenazine and deutetrabenazine, are the cornerstone of pharmacological management, supported by other medications and non-pharmacological strategies to optimize patient outcomes.

References

Caroff SN. Overcoming barriers to effective management of tardive dyskinesia. Neuropsychiatr Dis Treat. 2019;15:785-794. Published 2019 Apr 4. doi:10.2147/NDT.S19654.

Correll CU, Citrome L. Measurement-based Diagnosis and Treatment for Tardive Dyskinesia. J Clin Psychiatry. 2021;82(5):NU20016AH2C. Published 2021 Aug 31. doi:10.4088/JCP.NU20016AH2C.

INGREZZA® (valbenazine) capsules (package insert). San Diego, CA; Neurocrine Biosciences. 2024.

Pardis P, Remington G, Panda R, Lemez M, Agid O. Clozapine and tardive dyskinesia in patients with schizophrenia: A systematic review. J Psychopharmacol. 2019;33(10):1187-1198. doi:10.1177/0269881119862535.

Ricciardi L, Pringsheim T, Barnes TRE, et al. Treatment Recommendations for Tardive Dyskinesia. Can J Psychiatry. 2019;64(6):388-399. doi:10.1177/0706743719828968.

Stearns J, Kominek C. Tardive Dyskinesia Medication Management: A review of current guideline recommendations and evidence-based literature on assessing and managing symptoms of TD when prescribing antipsychotics, including understood pathophysiology. MedCentral. Last updated April 2022. https://www.medcentral.com/neurology/tardive-dyskinesia/medication-management

Vaidyanathan, Sreelakshmi; Jaiswal, Suyog Vijay. Tardive Dyskinesia: Prevention and Newer Management Strategies. Annals of Indian Psychiatry. 2020;4(1):10-19. doi: 10.4103/aip.aip_29_20.

Tardive Dyskinesia in Patients With Schizophrenia vs Primary Mood Disorder

How do the risk factors, clinical presentation, and impact of tardive dyskinesia (TD) differ between patients with schizophrenia and those with primary mood disorders like bipolar disorder or major depressive disorder? Additionally, what strategies can be implemented to improve early recognition and intervention for TD, particularly in patient groups with lower levels of awareness, such as those with schizophrenia?

Overview

Tardive dyskinesia (TD) is a serious and often irreversible movement disorder caused by prolonged exposure to antipsychotic medications used to treat various psychiatric conditions, including schizophrenia, bipolar disorder, and major depressive disorder. The impact of TD on patients' quality of life and social functioning differs between those with schizophrenia and primary mood disorders (bipolar disorder and major depressive disorder).

Prevalence and Risk Factors

The prevalence of tardive dyskinesia (TD) among patients with schizophrenia is notably high. For example, a meta-analysis of 41 studies involving over 11,000 patients with a mean age of 43 years (two-thirds of whom were male) found that more than three-quarters of these patients were diagnosed with schizophrenia, and the prevalence of TD was 25% (Saklad, 2020). The risk of TD increases with longer antipsychotic treatment duration (McEvoy 2019).

Some evidence suggests that patients with schizophrenia are more likely to be on antipsychotic medications than those with primary mood disorders (McEvoy 2019). Schizophrenia patients often require long-term antipsychotic treatment to manage chronic symptoms​​ (McEvoy 2019). In contrast, mood disorders such as bipolar disorder and major depressive disorder typically involve less intensive and more episodic use of antipsychotics​​ (McEvoy 2019). This difference in medication use contributes to a higher prevalence of tardive dyskinesia in patients with schizophrenia (McEvoy 2019).

Furthermore, the TD rate was lower among those currently using second-generation antipsychotics (SGAs) compared to those using first-generation antipsychotics (FGAs), with rates of 21% and 30%, respectively (Saklad 2020). Additionally, the small number of patients using SGAs without any prior exposure to FGAs had a prevalence rate of only 7.2% (Saklad 2020).

Clinical Presentation

Some studies show that the clinical presentation of tardive dyskinesia (TD) varies between patients with schizophrenia and those with mood disorders. In patients with schizophrenia, TD tends to manifest as more severe and pervasive involuntary movements (McEvoy 2020). This is partly due to the higher doses and longer durations of antipsychotic treatment typically required for managing schizophrenia (McEvoy 2020). Conversely, patients with mood disorders may experience milder forms of TD, but the condition can still significantly impair their quality of life and functional abilities (McEvoy 2020).

Patients with TD may experience significantly worse health-related quality of life (HRQoL) and social withdrawal compared to those without TD (McEvoy & Gandhi SK 2019). This impact is more pronounced in physical HRQoL domains than in mental health domains (McEvoy & Gandhi SK 2019). A study on the effect of tardive dyskinesia (TD) on quality of life found that patients with schizophrenia and TD had the lowest HRQoL scores compared to those with bipolar disorder (BD) or major depressive disorder (MDD) (McEvoy & Gandhi SK 2019). The physical manifestations of TD, such as involuntary movements of the face and extremities, can severely impair daily functioning and social interactions, leading to increased social isolation and stigma (McEvoy & Gandhi 2019).

Awareness and Diagnosis

One of the critical potential differences in TD between these patient groups (schizophrenia vs primary mood disorder) is the level of awareness. Patients with schizophrenia often exhibit a lack of insight into their condition, including the presence of TD (McEvoy 2020 & Saklad 2020). This lack of awareness can delay diagnosis and treatment, exacerbating the severity of the disorder​ (McEvoy 2020 & Saklad 2020). Conversely, patients with mood disorders may be generally more aware of their symptoms, which can lead to earlier diagnosis and intervention (McEvoy 2020 & Saklad 2020).

Treatment Management

Management of TD involves balancing the need to control psychiatric symptoms with minimizing the risk of movement disorders. SGAs are preferred over FGAs due to their lower risk of TD. Additionally, vesicular monoamine transporter 2 (VMAT2) inhibitors, such as deutetrabenazine and valbenazine, have shown efficacy in reducing TD symptoms and are recommended for moderate to severe cases (Correll 2017 & McEvoy 2020). These medications offer a promising option for patients with both schizophrenia and mood disorders, although individual responses may vary. Clinicians must balance the benefits of antipsychotic treatment with the risk of developing TD, particularly when treating mood disorders where alternative therapies may be available​ (McEvoy 2020 & Saklad 2020).

Conclusion

TD significantly affects patients with schizophrenia and mood disorders, with a more severe impact observed in those with schizophrenia. Effective management requires early recognition, appropriate use of SGAs, and consideration of VMAT2 inhibitors to improve patient outcomes and quality of life.

References

Correll CU, Kane JM, Citrome LL. Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in Treatment. J Clin Psychiatry. 2017;78(8):1136-1147. doi:10.4088/JCP.tv17016ah4c

McEvoy JP. Psychosocial Implications of Tardive Dyskinesia in Patients With Mood Disorders Versus Schizophrenia. J Clin Psychiatry. 2019;80(6):NU18041BR2C. Published 2019 Dec 3. doi:10.4088/JCP.NU18041BR2C

McEvoy J, Gandhi SK, Rizio AA, et al. Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia. Qual Life Res. 2019;28(12):3303-3312. doi:10.1007/s11136-019-02269-8

McEvoy JP, Kremens DE. Early Recognition and Treatment of Tardive Dyskinesia in Patients With Mood Disorders and Schizophrenia. J Clin Psychiatry. 2020;81(1):NU18041AH5C. Published 2020 Jan 28. doi:10.4088/JCP.NU18041AH5C

Saklad SR. Identifying Tardive Dyskinesia: Risk Factors, Functional Impact, and Diagnostic Tools. J Clin Psychiatry. 2020;81(1):TV18059BR1C. Published 2020 Jan 14. doi:10.4088/JCP.TV18059BR1C