TD is a clinical diagnosis based on a history of exposure to dopamine receptor-blocking agents, clinical observation of characteristic involuntary movements, and an absence of other conditions that might cause the signs and symptoms.
Be vigilant and judicious when prescribing drugs that could potentially block dopamine receptors.
For patients being treated with antipsychotics for conditions such as bipolar disorder or schizophrenia, at each visit assess for the symptoms of TD as part of the usual follow-up.[6]Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020 Sep 1;177(9):868-72.
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.177901
http://www.ncbi.nlm.nih.gov/pubmed/32867516?tool=bestpractice.com
[12]Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2):19cs12983.
http://www.ncbi.nlm.nih.gov/pubmed/31995677?tool=bestpractice.com
[31]National Institute for Health and Care Excellence. Bipolar disorder: assessment and management. February 2020 [internet publication].
https://www.nice.org.uk/guidance/cg185
[32]National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. March 2014 [internet publication].
https://www.nice.org.uk/guidance/cg178
Use the Abnormal Involuntary Movement Scale for a structured assessment or use a semi-structured assessment, which should include the patient's (or carer's) account of abnormal movement and visual observation of psychomotor abnormalities.[4]Bashir HH, Jankovic J. Treatment of tardive dyskinesia. Neurol Clin. 2020 May;38(2):379-96.
http://www.ncbi.nlm.nih.gov/pubmed/32279716?tool=bestpractice.com
[12]Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2):19cs12983.
http://www.ncbi.nlm.nih.gov/pubmed/31995677?tool=bestpractice.com
Consider other conditions that may mimic TD, such as tic disorder, levodopa-induced dyskinesia in patients with Parkinson's disease (drug-induced parkinsonism), facial chorea in patients with Huntington's disease, dystonia, stroke, severe hypoglycaemia, and other hyperkinetic movement disorders.[1]Savitt D, Jankovic J. Tardive syndromes. J Neurol Sci. 2018 Jun 15;389:35-42.
http://www.ncbi.nlm.nih.gov/pubmed/29506749?tool=bestpractice.com
[3]Friedman JH. Tardive syndromes. Continuum (Minneap Minn). 2019 Aug;25(4):1081-98.
http://www.ncbi.nlm.nih.gov/pubmed/31356294?tool=bestpractice.com
[12]Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2):19cs12983.
http://www.ncbi.nlm.nih.gov/pubmed/31995677?tool=bestpractice.com
History
Consider TD in a patient presenting with stereotypic involuntary oro-bucco-lingual movements that occur over a period of at least 4 weeks following use of a dopamine receptor-blocking agent for at least 3 months (or at least 1 month in people aged >60 years).[2]American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.
https://www.psychiatry.org/psychiatrists/practice/dsm
Although some drugs may cause TD after only a few days or weeks of exposure, there is usually a history of months of exposure (at least 3 months).
Signs and symptoms may develop during exposure to or following withdrawal of a causative drug (within 4 weeks of withdrawal from an oral drug, or within 8 weeks from a long-acting injectable drug).[2]American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.
https://www.psychiatry.org/psychiatrists/practice/dsm
Presentations can vary and there is a range in severity of symptoms.[4]Bashir HH, Jankovic J. Treatment of tardive dyskinesia. Neurol Clin. 2020 May;38(2):379-96.
http://www.ncbi.nlm.nih.gov/pubmed/32279716?tool=bestpractice.com
Take a comprehensive drug history, which may require a review of pharmacy or hospital records. This is one of the key aspects of diagnosing TD. Carefully document all drugs used in the past, even if the patient denies prior use of any dopamine receptor-blocking agents.
Antipsychotics (particularly typical antipsychotics) are the usual causative agents.[11]Ricciardi L, Pringsheim T, Barnes TRE, et al. Treatment recommendations for tardive dyskinesia. Can J Psychiatry. 2019 Jun;64(6):388-99.
https://journals.sagepub.com/doi/10.1177/0706743719828968
http://www.ncbi.nlm.nih.gov/pubmed/30791698?tool=bestpractice.com
[12]Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2):19cs12983.
http://www.ncbi.nlm.nih.gov/pubmed/31995677?tool=bestpractice.com
Several other drugs may also result in TD, for example:[5]Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013 Jul 12:3:tre-03-161-4138-1.
https://tremorjournal.org/articles/10.5334/tohm.165
http://www.ncbi.nlm.nih.gov/pubmed/23858394?tool=bestpractice.com
[13]D'Abreu A, Friedman JH. Tardive dyskinesia-like syndrome due to drugs that do not block dopamine receptors: rare or non-existent: literature review. Tremor Other Hyperkinet Mov (N Y). 2018 Aug 31:8:570.
https://tremorjournal.org/articles/10.5334/tohm.438
http://www.ncbi.nlm.nih.gov/pubmed/30191087?tool=bestpractice.com
Chronic use of prokinetic agents (e.g., metoclopramide)
Selective serotonin-reuptake inhibitors (e.g., citalopram)
Serotonin-noradrenaline reuptake inhibitors (e.g., duloxetine)
Tricyclic antidepressants (e.g., amitriptyline)
Lithium
Cinnarizine (an antihistamine/calcium antagonist).
Consult your local drug formulary for a full list of drugs that may cause TD.
Consider the following weaker risk factors in your history taking, although these are not sufficient alone to make a diagnosis of TD:[3]Friedman JH. Tardive syndromes. Continuum (Minneap Minn). 2019 Aug;25(4):1081-98.
http://www.ncbi.nlm.nih.gov/pubmed/31356294?tool=bestpractice.com
[4]Bashir HH, Jankovic J. Treatment of tardive dyskinesia. Neurol Clin. 2020 May;38(2):379-96.
http://www.ncbi.nlm.nih.gov/pubmed/32279716?tool=bestpractice.com
[5]Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013 Jul 12:3:tre-03-161-4138-1.
https://tremorjournal.org/articles/10.5334/tohm.165
http://www.ncbi.nlm.nih.gov/pubmed/23858394?tool=bestpractice.com
[6]Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020 Sep 1;177(9):868-72.
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.177901
http://www.ncbi.nlm.nih.gov/pubmed/32867516?tool=bestpractice.com
[11]Ricciardi L, Pringsheim T, Barnes TRE, et al. Treatment recommendations for tardive dyskinesia. Can J Psychiatry. 2019 Jun;64(6):388-99.
https://journals.sagepub.com/doi/10.1177/0706743719828968
http://www.ncbi.nlm.nih.gov/pubmed/30791698?tool=bestpractice.com
Age >50 years
Post-menopause
African-American ethnicity
Diabetes mellitus
Brain/central nervous system injury
Dementia
Smoking
Alcohol and substance misuse.
Rule out any history of trauma or surgery in the oro-bucco-lingual region. Although rare, patients may develop dyskinesia after peripheral injury to this area or after a dental procedure (edentulous dyskinesia).[33]Lenka A, Jankovic J. Peripherally-induced movement disorders: an update. Tremor Other Hyperkinet Mov (N Y). 2023 Mar 28:13:8.
https://tremorjournal.org/articles/10.5334/tohm.758
http://www.ncbi.nlm.nih.gov/pubmed/37008994?tool=bestpractice.com
In a patient taking antipsychotics (or other potentially causative drugs), ask the patient or their family members or carers about the onset of the involuntary movements, any precipitants, and the impact on their overall health and quality of life.[6]Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020 Sep 1;177(9):868-72.
https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.177901
http://www.ncbi.nlm.nih.gov/pubmed/32867516?tool=bestpractice.com
Physical examination
Visually assess the patient. Evaluate the patient for stereotypic involuntary movements involving the mouth and tongue (commonly referred to as oro-buccal-lingual dyskinesia). These may include:
There are, however, many other types of involuntary movements, such as dystonia, tardive akathisia, tardive tremor, tardive tics (tourettism), tardive myoclonus, tardive chorea, and tardive parkinsonism that may be part of TD phenomenology. Some patients may have blepharospasm or transiently sustained jaw opening, deviation, or closure with jaw clenching and teeth grinding (bruxism) as part of cranial tardive dystonia.[3]Friedman JH. Tardive syndromes. Continuum (Minneap Minn). 2019 Aug;25(4):1081-98.
http://www.ncbi.nlm.nih.gov/pubmed/31356294?tool=bestpractice.com
[5]Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013 Jul 12:3:tre-03-161-4138-1.
https://tremorjournal.org/articles/10.5334/tohm.165
http://www.ncbi.nlm.nih.gov/pubmed/23858394?tool=bestpractice.com
Patients may also develop tardive dystonia of the arms, legs, and trunk; the latter typically manifested by trunk arching (opisthotonus). Rarely, patients may develop choreic and athetoid movements of the trunk and limbs.[3]Friedman JH. Tardive syndromes. Continuum (Minneap Minn). 2019 Aug;25(4):1081-98.
http://www.ncbi.nlm.nih.gov/pubmed/31356294?tool=bestpractice.com
[5]Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013 Jul 12:3:tre-03-161-4138-1.
https://tremorjournal.org/articles/10.5334/tohm.165
http://www.ncbi.nlm.nih.gov/pubmed/23858394?tool=bestpractice.com
Some patients also develop chronic painful oral and genital sensations, which are termed tardive pain.[4]Bashir HH, Jankovic J. Treatment of tardive dyskinesia. Neurol Clin. 2020 May;38(2):379-96.
http://www.ncbi.nlm.nih.gov/pubmed/32279716?tool=bestpractice.com
Carefully document (preferably video) the involuntary movements. Rate the severity of the involuntary movements, for example, with the Abnormal Involuntary Movement Scale (AIMS) or Impact-TD.[34]Munetz MR, Benjamin S. How to examine patients using the Abnormal Involuntary Movement Scale. Hosp Community Psychiatry. 1988 Nov;39(11):1172-7.
http://www.ncbi.nlm.nih.gov/pubmed/2906320?tool=bestpractice.com
Consider referring the patient for a neurological consultation if unsure about the possible diagnosis of TD.[12]Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2):19cs12983.
http://www.ncbi.nlm.nih.gov/pubmed/31995677?tool=bestpractice.com
For example, due to an atypical presentation, a family history of other movement or neurodegenerative disorders (such as Huntington's disease), symptoms present of another neurological condition, or an unexpected response to treatment.[12]Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2):19cs12983.
http://www.ncbi.nlm.nih.gov/pubmed/31995677?tool=bestpractice.com
Investigations
Do not routinely request investigations if a patient has the classic signs and symptoms of TD in the context of long-term use of causative drugs.
In patients with atypical features, consider appropriate investigations to rule out potential secondary causes. For example, in patients with:
Abrupt onset of symptoms or unilateral symptoms, request an urgent head computed tomography (CT) scan or magnetic resonance imaging (MRI) to rule out serious conditions such as stroke or severe hyperglycaemia (causing diabetic striatopathy).[35]Xu Y, Shi Q, Yue Y, et al. Clinical and imaging features of diabetic striatopathy: report of 6 cases and literature review. Neurol Sci. 2022 Oct;43(10):6067-77.
https://link.springer.com/article/10.1007/s10072-022-06342-y
http://www.ncbi.nlm.nih.gov/pubmed/35965280?tool=bestpractice.com
The authors of this topic also recommend a comprehensive metabolic panel to rule out metabolic derangements.[36]Espay AJ. Neurologic complications of electrolyte disturbances and acid-base balance. Handb Clin Neurol. 2014;119:365-82.
http://www.ncbi.nlm.nih.gov/pubmed/24365306?tool=bestpractice.com
Cognitive impairment or eye movement abnormalities, request investigations for neurodegenerative conditions such as Huntington's disease (HD) and HD-like conditions. These include CAG repeat length, peripheral smear for acanthocytes, and MRI of the brain to look for caudate or striatal atrophy.