Evidence-Based Strategies for Managing Tardive Dyskinesia

Joseph P. McEvoy, MD

J Clin Psychiatry 2018;79(1):NU16048CC2C

Article Abstract

Do you know how to manage tardive dyskinesia symptoms? In this Case and Comment activity, consider the case of John, a 25-year-old project manager diagnosed with bipolar disorder who has begun exhibiting symptoms of uncontrollable movement.

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Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University
Supported by an educational grant from Neurocrine Biosciences, Inc.

Case Introduction

John* is a 25-year-old African American man who works for a graphic design company. He has worked for the company for the past 3 years and was promoted to project manager 6 months ago.

John was diagnosed with bipolar disorder 5 years ago after experiencing a manic episode during summer break in college. During this episode, John exhibited symptoms of (1) euphoria (which led to a period of time in which he did not sleep for more than 3 hours per night), (2) impulsivity (which manifested in a spur-of-the-moment trip to Las Vegas with some members of his fraternity, where he lost $400 at a casino), and (3) distractibility (during which time he frequently “lost track of time” and forgot to go to his summer job, resulting in his termination).¹ He had previously been referred to a psychiatrist when he was 18 years old for a depressive episode that lasted 3 months. At that appointment, John reported that his father had struggled with bipolar disorder his entire life, which had ultimately led to periods of unemployment and disruptions, both financial and emotional, and a decreased quality of life for the rest of the family.

John’s treating psychiatrist resolved this manic episode with 1500 mg/d of lithium² and 5 mg/d of haloperidol.³ Guidelines suggest lithium⁴ as initial treatment for patients diagnosed with bipolar disorder, and haloperidol has shown efficacy in reducing symptoms of mania when compared to second-generation antipsychotics (SGAs).⁵ For long-term maintenance treatment, the dosages were decreased to 1000 mg/d of lithium and 2 mg/d of haloperidol.

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

References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Washington, DC: American Psychiatric Publishing; 2013.
Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217:266–280. PubMed
Cipriani A, Rendell JM, Geddes JR. Haloperidol alone or in combination for acute mania. Cochrane Database Syst Rev. 2006;(3):CD004362. PubMed
Connolly KR, Thase ME. The clinical management of bipolar disorder: a review of evidence-based guidelines. Prim Care Companion CNS Disord. 2011;13(4):10r01097. PubMed
Goikolea JM, Colom F, Capapey J, et al. Faster onset of antimanic action with haloperidol compared to second-generation antipsychotics: a meta-analysis of randomized clinical trials in acute mania. Eur Neuropsychopharmacol. 2013;23(4):305–316. PubMed

Patient Presentation

John’s promotion was accompanied by relocation to a new city, and he was referred to you by his previous treating psychiatrist. He has been on his current treatment regimen for 5 years. John presents to you with no complaints about his treatment, but you notice some mild pursing movements of his lips and choreiform movements of his hands. When you inquire about these movements, John states that he has been stressed lately due to the move and new job, and he assumed that they would go away in time.

You administer the Abnormal Involuntary Movement Scale (AIMS) and discover that John scores a 2 in both the “Facial and Oral Movements” and “Extremity Movements” categories, which indicates mild symptom severity of tardive dyskinesia (TD).

Given his treatment history, what is the best next treatment step for John?

Discontinue haloperidol and switch to an SGA
Decrease lithium to 500 mg/d
Decrease haloperidol dosage to 0.5 mg/d
Discontinue lithium and begin treatment with a selective serotonin reuptake inhibitor (SSRI)

Explanation

The correct answer is a. Discontinue haloperidol and switch to an SGA.

Patients who are treated with long-term haloperidol may be at a higher risk for developing TD symptoms than those taking SGAs.¹ Decreasing haloperidol to 0.5 mg/d is an incorrect response because clinicians should discontinue first-generation antipsychotic (FGA) treatment when TD symptoms occur, rather than decrease dosage.² Because John has been taking this medication for 5 years and is African American, his risk of developing TD symptoms may be elevated.³ Additional risk factors that can increase a patient’s chance of developing TD symptoms are older age, female sex, preexisting mood disorder, cognitive disturbance, alcohol or substance abuse, diabetes, HIV positivity, and the early occurrence of extrapyramidal side effects.⁴

Decreasing lithium to 500 mg/d is incorrect because it falls below the recommended dosage of 900 mg/d, and lithium is not associated with an increased risk of TD.⁵ Discontinuing lithium and beginning treatment with an SSRI is also incorrect, as lithium has shown some efficacy in protecting against TD symptoms during long-term antipsychotic treatment.⁶ Additionally, research suggests that in patients diagnosed with bipolar disorder, antidepressants may trigger a manic episode.⁷

You discontinue haloperidol and replace it with 10 mg/d of aripiprazole, and you add 50 mg of pyridoxine twice daily because vitamin B₆has shown efficacy in reducing TD symptoms.⁸ As a result, John’s dyskinesia symptoms resolve substantially.

References

Carbon M, Hsieh CH, Kane JM, et al. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78(3):e264–e278. Full Text
Kaspar R, Ellingrod VL. Strategies for managing drug-induced tardive dyskinesia. Curr Psychiatry. 2014;13(3):44–46.
Neppe VM. Tardive dyskinesia revisited: a clinical priority: perspective-diagnosis and assessment (part A). J Psychol Clin Psychiatry. 2016;6(2):00348.
Correll CU. Epidemiology and Prevention of Tardive Dyskinesia. J Clin Psychiatry. 2017. Full Text
Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Hyperkinetic Mov. 2013;3:tre-03-161-4138-1. PubMed
van Harten PN, Hoek HW, Matroos GE, et al. Evidence that lithium protects against tardive dyskinesia: the Curaçao Extrapyramidal syndromes study VI. Eur Neuropsychopharmacol. 2008;18(2):152–155. PubMed
Baldessarini RJ, Faedda GL, Offidani E, et al. Switching of mood from depression to mania with antidepressants. Psychiatric Times. November 8, 2013.
Lerner V, Miodownik C, Kaptsan A, et al. Vitamin B6 treatment for tardive dyskinesia: a randomized, double-blind, placebo-controlled, crossover study. J Clin Psychiatry. 2007;68(11):1648–1654. Abstract